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Volume 34Issue 3June 2021

EDITOR IN CHIEF: Dr. Jo-Anne H. Young

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Editor in Chief

CMR EiC Young
Dr. Jo-Anne H. Young

Editor in Chief (2022) | University of Minnesota

Jo-Anne H. Young is a Professor of Medicine and Medical Director of the Program in Adult Transplant Infectious Disease at the University of Minnesota.

Editorial Board

  • Clinical Microbiology ReviewsArticle
    Global Epidemiology of Campylobacter Infection

    SUMMARY

    Campylobacter jejuni infection is one of the most widespread infectious diseases of the last century. The incidence and prevalence of campylobacteriosis have increased in both developed and developing countries over the last 10 years. The dramatic increase in North America, Europe, and Australia is alarming, and data from parts of Africa, Asia, and the Middle East indicate that campylobacteriosis is endemic in these areas, especially in children. In addition to C. jejuni, there is increasing recognition of the clinical importance of emerging Campylobacter species, including Campylobacter concisus and Campylobacter ureolyticus. Poultry is a major reservoir and source of transmission of campylobacteriosis to humans. Other risk factors include consumption of animal products and water, contact with animals, and international travel. Strategic implementation of multifaceted biocontrol measures to reduce the transmission of this group of pathogens is paramount for public health. Overall, campylobacteriosis is still one of the most important infectious diseases that is likely to challenge global health in the years to come. This review provides a comprehensive overview of the global epidemiology, transmission, and clinical relevance of Campylobacter infection.

    REFERENCES

    1.
    Man SM. 2011. The clinical importance of emerging Campylobacter species. Nat Rev Gastroenterol Hepatol 8:669–685.
    2.
    Vandamme P, Dewhirst FE, Paster BJ, On SLW. 2005. Campylobacteraceae, p 1147–1160. In Garrity GM, Brenner DJ, Krieg NR, Staley JT (ed), Bergey's manual of systematic bacteriology, vol 2. Springer Science, New York, NY.
    3.
    Sebald M, Veron M. 1963. Base DNA content and classification of vibrios. Ann Inst Pasteur (Paris) 105:897–910.
    4.
    Black RE, Levine MM, Clements ML, Hughes TP, Blaser MJ. 1988. Experimental Campylobacter jejuni infection in humans. J Infect Dis 157:472–479.
    5.
    Hara-Kudo Y, Takatori K. 2011. Contamination level and ingestion dose of foodborne pathogens associated with infections. Epidemiol Infect 139:1505–1510.
    6.
    Medema GJ, Teunis PF, Havelaar AH, Haas CN. 1996. Assessment of the dose-response relationship of Campylobacter jejuni. Int J Food Microbiol 30:101–111.
    7.
    Tribble DR, Baqar S, Scott DA, Oplinger ML, Trespalacios F, Rollins D, Walker RI, Clements JD, Walz S, Gibbs P, Burg EF, III, Moran AP, Applebee L, Bourgeois AL. 2010. Assessment of the duration of protection in Campylobacter jejuni experimental infection in humans. Infect Immun 78:1750–1759.
    8.
    Kirkpatrick BD, Lyon CE, Porter CK, Maue AC, Guerry P, Pierce KK, Carmolli MP, Riddle MS, Larsson CJ, Hawk D, Dill EA, Fingar A, Poly F, Fimlaid K, Hoq F, Tribble DR. 2013. Lack of homologous protection against Campylobacter jejuni CG8421 in a human challenge model. Clin Infect Dis 57:1106–1113.
    9.
    Baqar S, Tribble DR, Carmolli M, Sadigh K, Poly F, Porter C, Larsson CJ, Pierce KK, Guerry P, Darsley M, Kirkpatrick B. 2010. Recrudescent Campylobacter jejuni infection in an immunocompetent adult following experimental infection with a well-characterized organism. Clin Vaccine Immunol 17:80–86.
    10.
    Blaser MJ. 1997. Epidemiologic and clinical features of Campylobacter jejuni infections. J Infect Dis 176(Suppl 2):S103–S105.
    11.
    Nielsen HL, Ejlertsen T, Engberg J, Nielsen H. 2013. High incidence of Campylobacter concisus in gastroenteritis in North Jutland, Denmark: a population-based study. Clin Microbiol Infect 19:445–450.
    12.
    Bessede E, Lehours P, Labadi L, Bakiri S, Megraud F. 2014. Comparison of characteristics of patients infected by Campylobacter jejuni, Campylobacter coli, and Campylobacter fetus. J Clin Microbiol 52:328–330.
    13.
    Rao MR, Naficy AB, Savarino SJ, Abu-Elyazeed R, Wierzba TF, Peruski LF, Abdel-Messih I, Frenck R, Clemens JD. 2001. Pathogenicity and convalescent excretion of Campylobacter in rural Egyptian children. Am J Epidemiol 154:166–173.
    14.
    Inglis GD, Boras VF, Houde A. 2011. Enteric campylobacteria and RNA viruses associated with healthy and diarrheic humans in the Chinook Heath Region of Southwestern Alberta, Canada. J Clin Microbiol 49:209–219.
    15.
    Karmali MA, Penner JL, Fleming PC, Williams A, Hennessy JN. 1983. The serotype and biotype distribution of clinical isolates of Campylobacter jejuni and Campylobacter coli over a three-year period. J Infect Dis 147:243–246.
    16.
    Gurtler M, Alter T, Kasimir S, Fehlhaber K. 2005. The importance of Campylobacter coli in human campylobacteriosis: prevalence and genetic characterization. Epidemiol Infect 133:1081–1087.
    17.
    Hamidian M, Sanaei M, Bolfion M, Dabiri H, Zali MR, Walther-Rasmussen J. 2011. Prevalence of putative virulence markers in Campylobacter jejuni and Campylobacter coli isolated from hospitalized children, raw chicken, and raw beef in Tehran, Iran. Can J Microbiol 57:143–148.
    18.
    Friedman CR, Hoekstra RM, Samuel M, Marcus R, Bender J, Shiferaw B, Reddy S, Ahuja SD, Helfrick DL, Hardnett F, Carter M, Anderson B, Tauxe RV. 2004. Risk factors for sporadic Campylobacter infection in the United States: a case-control study in FoodNet sites. Clin Infect Dis 38(Suppl 3):S285–S296.
    19.
    Adak GK, Meakins SM, Yip H, Lopman BA, O'Brien SJ. 2005. Disease risks from foods, England and Wales, 1996–2000. Emerg Infect Dis 11:365–372.
    20.
    Hall G, Kirk MD, Becker N, Gregory JE, Unicomb L, Millard G, Stafford R, Lalor K. 2005. Estimating foodborne gastroenteritis, Australia. Emerg Infect Dis 11:1257–1264.
    21.
    Tam CC, O'Brien SJ, Tompkins DS, Bolton FJ, Berry L, Dodds J, Choudhury D, Halstead F, Iturriza-Gomara M, Mather K, Rait G, Ridge A, Rodrigues LC, Wain J, Wood B, Gray JJ. 2012. Changes in causes of acute gastroenteritis in the United Kingdom over 15 years: microbiologic findings from 2 prospective, population-based studies of infectious intestinal disease. Clin Infect Dis 54:1275–1286.
    22.
    Casanova C, Schweiger A, von Steiger N, Droz S, Marschall J. 2015. Campylobacter concisus pseudo-outbreak caused by improved culture conditions. J Clin Microbiol 53:660–662.
    23.
    Nielsen HL, Engberg J, Ejlertsen T, Bucker R, Nielsen H. 2012. Short-term and medium-term clinical outcomes of Campylobacter concisus infection. Clin Microbiol Infect 18:E459–E465.
    24.
    Nielsen HL, Engberg J, Ejlertsen T, Nielsen H. 2013. Evaluation of fecal calprotectin in Campylobacter concisus and Campylobacter jejuni/coli gastroenteritis. Scand J Gastroenterol 48:633–635.
    25.
    Sadkowska-Todys M, Kucharczyk B. 2012. Campylobacteriosis in Poland in 2010. Przegl Epidemiol 66:255–258.
    26.
    Kubota K, Kasuga F, Iwasaki E, Inagaki S, Sakurai Y, Komatsu M, Toyofuku H, Angulo FJ, Scallan E, Morikawa K. 2011. Estimating the burden of acute gastroenteritis and foodborne illness caused by Campylobacter, Salmonella, and Vibrio parahaemolyticus by using population-based telephone survey data, Miyagi Prefecture, Japan, 2005 to 2006. J Food Prot 74:1592–1598.
    27.
    Wagenaar JA, French NP, Havelaar AH. 2013. Preventing Campylobacter at the source: why is it so difficult? Clin Infect Dis 57:1600–1606.
    28.
    Havelaar AH, van Pelt W, Ang CW, Wagenaar JA, van Putten JP, Gross U, Newell DG. 2009. Immunity to Campylobacter: its role in risk assessment and epidemiology. Crit Rev Microbiol 35:1–22.
    29.
    Tompkins DS, Hudson MJ, Smith HR, Eglin RP, Wheeler JG, Brett MM, Owen RJ, Brazier JS, Cumberland P, King V, Cook PE. 1999. A study of infectious intestinal disease in England: microbiological findings in cases and controls. Commun Dis Public Health 2:108–113.
    30.
    de Wit MA, Koopmans MP, Kortbeek LM, Wannet WJ, Vinje J, van Leusden F, Bartelds AI, van Duynhoven YT. 2001. Sensor, a population-based cohort study on gastroenteritis in the Netherlands: incidence and etiology. Am J Epidemiol 154:666–674.
    31.
    Little CL, Gormley FJ, Rawal N, Richardson JF. 2010. A recipe for disaster: outbreaks of campylobacteriosis associated with poultry liver pate in England and Wales. Epidemiol Infect 138:1691–1694.
    32.
    Batz MB, Hoffmann S, Morris JG, Jr. 2012. Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elicitation. J Food Prot 75:1278–1291.
    33.
    Hall AJ, Wikswo ME, Manikonda K, Roberts VA, Yoder JS, Gould LH. 2013. Acute gastroenteritis surveillance through the National Outbreak Reporting System, United States. Emerg Infect Dis 19:1305–1309.
    34.
    Gilliss D, Cronquist AB, Cartter M, Tobin-D'Angelo M, Blythe D, Smith K, Lathrop S, Zansky S, Cieslak PR, Dunn J, Holt KG, Lance S, Crim SM, Henao OL, Patrick M, Griffin PM, Tauxe RV. 2013. Incidence and trends of infection with pathogens transmitted commonly through food—foodborne diseases active surveillance network, 10 U.S. sites, 1996–2012. MMWR Morb Mortal Wkly Rep 62:283–287.
    35.
    Hoffmann S, Batz MB, Morris JG, Jr. 2012. Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens. J Food Prot 75:1292–1302.
    36.
    Kendall ME, Crim S, Fullerton K, Han PV, Cronquist AB, Shiferaw B, Ingram LA, Rounds J, Mintz ED, Mahon BE. 2012. Travel-associated enteric infections diagnosed after return to the United States, Foodborne Diseases Active Surveillance Network (FoodNet), 2004–2009. Clin Infect Dis 54(Suppl 5):S480–S487.
    37.
    Arsenault J, Berke O, Michel P, Ravel A, Gosselin P. 2012. Environmental and demographic risk factors for campylobacteriosis: do various geographical scales tell the same story? BMC Infect Dis 12:318.
    38.
    Keegan VA, Majowicz SE, Pearl DL, Marshall BJ, Sittler N, Knowles L, Wilson JB. 2009. Epidemiology of enteric disease in C-EnterNet's pilot site—Waterloo region, Ontario, 1990 to 2004. Can J Infect Dis Med Microbiol 20:79–87.
    39.
    BC Centre for Disease Control. 2011, posting date. British Columbia annual summary of reportable diseases. BC Centre for Disease Control, Vancouver, British Columbia, Canada.
    40.
    Larrosa-Haro A, Macias-Rosales R, Sanchez-Ramirez CA, Cortes-Lopez MC, Aguilar-Benavides S. 2010. Seasonal variation of enteropathogens in infants and preschoolers with acute diarrhea in western Mexico. J Pediatr Gastroenterol Nutr 51:534–536.
    41.
    Benoit SR, Lopez B, Arvelo W, Henao O, Parsons MB, Reyes L, Moir JC, Lindblade K. 2014. Burden of laboratory-confirmed Campylobacter infections in Guatemala 2008–2012: results from a facility-based surveillance system. J Epidemiol Glob Health 4:51–59.
    42.
    Workman SN, Sobers SJ, Mathison GE, Lavoie MC. 2006. Human Campylobacter-associated enteritis on the Caribbean island of Barbados. Am J Trop Med Hyg 74:623–627.
    43.
    Fernández H. 2011. Campylobacter and campylobacteriosis: a view from South America. Rev Peru Med Exp Salud Publica 28:121–127.
    44.
    Collado L, Gutierrez M, Gonzalez M, Fernandez H. 2013. Assessment of the prevalence and diversity of emergent campylobacteria in human stool samples using a combination of traditional and molecular methods. Diagn Microbiol Infect Dis 75:434–436.
    45.
    Platts-Mills JA, Liu J, Gratz J, Mduma E, Amour C, Swai N, Taniuchi M, Begum S, Penataro Yori P, Tilley DH, Lee G, Shen Z, Whary MT, Fox JG, McGrath M, Kosek M, Haque R, Houpt ER. 2014. Detection of Campylobacter in stool and determination of significance by culture, enzyme immunoassay, and PCR in developing countries. J Clin Microbiol 52:1074–1080.
    46.
    Havelaar AH, Ivarsson S, Lofdahl M, Nauta MJ. 2013. Estimating the true incidence of campylobacteriosis and salmonellosis in the European Union, 2009. Epidemiol Infect 141:293–302.
    47.
    Tam CC, Rodrigues LC, Viviani L, Dodds JP, Evans MR, Hunter PR, Gray JJ, Letley LH, Rait G, Tompkins DS, O'Brien SJ. 2012. Longitudinal study of infectious intestinal disease in the UK (IID2 study): incidence in the community and presenting to general practice. Gut 61:69–77.
    48.
    Stingl K, Knüver MT, Vogt P, Buhler C, Krüger NJ, Alt K, Tenhagen BA, Hartung M, Schroeter A, Ellerbroek L, Appel B, Käsbohrer A. 2012. Quo vadis? Monitoring Campylobacter in Germany. Eur J Microbiol Immunol 2:88–96.
    49.
    Hauri AM, Just M, McFarland S, Schweigmann A, Schlez K, Krahn J. 2013. Campylobacteriosis outbreaks in the state of Hesse, Germany, 2005–2011: raw milk yet again. Dtsch Med Wochenschr 138:357–361.
    50.
    Sadkowska-Todys M, Kucharczyk B. 2014. Campylobacteriosis in Poland in 2012. Przegl Epidemiol 68:239–241, 249–251.
    51.
    Bouwknegt M, van Pelt W, Havelaar AH. 2013. Scoping the impact of changes in population age-structure on the future burden of foodborne disease in the Netherlands, 2020–2060. Int J Environ Res Public Health 10:2888–2896.
    52.
    Havelaar AH, Nauta MJ, Mangen MJJ, de Koeijer AG, Bogaardt M-J, Evers EG, Jacobs-Reitsma WF, van Pelt W, Wagenaar JA, de Wit GA, van der Zee H. 29 July 2005, posting date. Costs and benefits of controlling Campylobacter in the Netherlands—integrating risk analysis, epidemiology and economics. National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
    53.
    Sivadon-Tardy V, Porcher R, Orlikowski D, Ronco E, Gault E, Roussi J, Durand MC, Sharshar T, Annane D, Raphael JC, Megraud F, Gaillard JL. 2014. Increased incidence of Campylobacter jejuni-associated Guillain-Barre syndromes in the Greater Paris area. Epidemiol Infect 142:1609–1613.
    54.
    de Boer RF, Ott A, Guren P, van Zanten E, van Belkum A, Kooistra-Smid AM. 2013. Detection of Campylobacter species and Arcobacter butzleri in stool samples by use of real-time multiplex PCR. J Clin Microbiol 51:253–259.
    55.
    Nielsen HL, Engberg J, Ejlertsen T, Nielsen H. 2013. Clinical manifestations of Campylobacter concisus infection in children. Pediatr Infect Dis J 32:1194–1198.
    56.
    Ferreira S, Julio C, Queiroz JA, Domingues FC, Oleastro M. 2014. Molecular diagnosis of Arcobacter and Campylobacter in diarrhoeal samples among Portuguese patients. Diagn Microbiol Infect Dis 78:220–225.
    57.
    Koziel M, Kiely R, Blake L, O'Callaghan I, Corcoran GD, Lucey B, Sleator RD. 2013. Improved detection of bacterial pathogens in patients presenting with gastroenteritis by use of the EntericBio real-time Gastro Panel I assay. J Clin Microbiol 51:2679–2685.
    58.
    Bullman S, Corcoran D, O'Leary J, Lucey B, Byrne D, Sleator RD. 2011. Campylobacter ureolyticus: an emerging gastrointestinal pathogen? FEMS Immunol Med Microbiol 61:228–230.
    59.
    Bullman S, Corcoran D, O'Leary J, O'Hare D, Lucey B, Sleator RD. 2011. Emerging dynamics of human campylobacteriosis in southern Ireland. FEMS Immunol Med Microbiol 63:248–253.
    60.
    Huang JL, Xu HY, Bao GY, Zhou XH, Ji DJ, Zhang G, Liu PH, Jiang F, Pan ZM, Liu XF, Jiao XA. 2009. Epidemiological surveillance of Campylobacter jejuni in chicken, dairy cattle and diarrhoea patients. Epidemiol Infect 137:1111–1120.
    61.
    Chen J, Sun XT, Zeng Z, Yu YY. 2011. Campylobacter enteritis in adult patients with acute diarrhea from 2005 to 2009 in Beijing, China. Chin Med J (Engl) 124:1508–1512.
    62.
    Wang J, Guo YC, Li N. 2013. Prevalence and risk assessment of Campylobacter jejuni in chicken in China. Biomed Environ Sci 26:243–248.
    63.
    Mukherjee P, Ramamurthy T, Bhattacharya MK, Rajendran K, Mukhopadhyay AK. 2013. Campylobacter jejuni in hospitalized patients with diarrhea, Kolkata, India. Emerg Infect Dis 19:1155–1156.
    64.
    Sinha A, SenGupta S, Guin S, Dutta S, Ghosh S, Mukherjee P, Mukhopadhyay AK, Ramamurthy T, Takeda Y, Kurakawa T, Nomoto K, Nair GB, Nandy RK. 2013. Culture-independent real-time PCR reveals extensive polymicrobial infections in hospitalized diarrhoea cases in Kolkata, India. Clin Microbiol Infect 19:173–180.
    65.
    Rajendran P, Babji S, George AT, Rajan DP, Kang G, Ajjampur SS. 2012. Detection and species identification of Campylobacter in stool samples of children and animals from Vellore, South India. Indian J Med Microbiol 30:85–88.
    66.
    Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acacio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM. 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382:209–222.
    67.
    Weinberger M, Lerner L, Valinsky L, Moran-Gilad J, Nissan I, Agmon V, Peretz C. 2013. Increased incidence of Campylobacter spp. infection and high rates among children, Israel. Emerg Infect Dis 19:1828–1831.
    68.
    Dayan N, Revivo D, Even L, Elkayam O, Glikman D. 2010. Campylobacter is the leading cause of bacterial gastroenteritis and dysentery in hospitalized children in the Western Galilee Region in Israel. Epidemiol Infect 138:1405–1406.
    69.
    OzFoodNet Working Group. 2012. Monitoring the incidence and causes of diseases potentially transmitted by food in Australia: annual report of the OzFoodNet network, 2010. Commun Dis Intell Q Rep 36:E213–E241.
    70.
    OzFoodNet Working Group. 2010. Monitoring the incidence and causes of diseases potentially transmitted by food in Australia: annual report of the OzFoodNet network, 2009. Commun Dis Intell Q Rep 34:396–426.
    71.
    OzFoodNet Working Group. 2009. Monitoring the incidence and causes of diseases potentially transmitted by food in Australia: annual report of the OzFoodNet network, 2008. Commun Dis Intell Q Rep 33:389–413.
    72.
    Gibney KB, O'Toole J, Sinclair M, Leder K. 2014. Disease burden of selected gastrointestinal pathogens in Australia, 2010. Int J Infect Dis 28:176–185.
    73.
    Sears A, Baker MG, Wilson N, Marshall J, Muellner P, Campbell DM, Lake RJ, French NP. 2011. Marked campylobacteriosis decline after interventions aimed at poultry, New Zealand. Emerg Infect Dis 17:1007–1015.
    74.
    Gilpin BJ, Walsh G, On SL, Smith D, Marshall JC, French NP. 2013. Application of molecular epidemiology to understanding campylobacteriosis in the Canterbury region of New Zealand. Epidemiol Infect 141:1253–1266.
    75.
    Cornelius AJ, Chambers S, Aitken J, Brandt SM, Horn B, On SL. 2012. Epsilonproteobacteria in humans, New Zealand. Emerg Infect Dis 18:510–512.
    76.
    Howard P, Alexander ND, Atkinson A, Clegg AO, Gerega G, Javati A, Kajoi M, Lupiwa S, Lupiwa T, Mens M, Saleu G, Sanders RC, West B, Alpers MP. 2000. Bacterial, viral and parasitic aetiology of paediatric diarrhoea in the highlands of Papua New Guinea. J Trop Pediatr 46:10–14.
    77.
    Mason J, Iturriza-Gomara M, O'Brien SJ, Ngwira BM, Dove W, Maiden MC, Cunliffe NA. 2013. Campylobacter infection in children in Malawi is common and is frequently associated with enteric virus co-infections. PLoS One 8:e59663.
    78.
    Randremanana RV, Randrianirina F, Sabatier P, Rakotonirina HC, Randriamanantena A, Razanajatovo IM, Ratovoson R, Richard V. 2014. Campylobacter infection in a cohort of rural children in Moramanga, Madagascar. BMC Infect Dis 14:372.
    79.
    Swierczewski BE, Odundo EA, Koech MC, Ndonye JN, Kirera RK, Odhiambo CP, Cheruiyot EK, Shaffer DN, Ombogo AN, Oaks EV. 2013. Enteric pathogen surveillance in a case-control study of acute diarrhea in Kisii Town, Kenya. J Med Microbiol 62:1774–1776.
    80.
    Lastovica A. 2006. Emerging Campylobacter spp.: the tip of the iceberg. Clin Microbiol Newsl 28:49–56.
    81.
    Lastovica AJ. 2009. Clinical relevance of Campylobacter concisus isolated from pediatric patients. J Clin Microbiol 47:2360.
    82.
    Man SM, Kaakoush NO, Mitchell HM. 2011. The role of bacteria and pattern-recognition receptors in Crohn's disease. Nat Rev Gastroenterol Hepatol 8:152–168.
    83.
    Blaser MJ, Hoverson D, Ely IG, Duncan DJ, Wang WL, Brown WR. 1984. Studies of Campylobacter jejuni in patients with inflammatory bowel disease. Gastroenterology 86:33–38.
    84.
    Weber P, Koch M, Heizmann WR, Scheurlen M, Jenss H, Hartmann F. 1992. Microbic superinfection in relapse of inflammatory bowel disease. J Clin Gastroenterol 14:302–308.
    85.
    Boyanova L, Gergova G, Spassova Z, Koumanova R, Yaneva P, Mitov I, Derejian S, Krastev Z. 2004. Campylobacter infection in 682 Bulgarian patients with acute enterocolitis, inflammatory bowel disease, and other chronic intestinal diseases. Diagn Microbiol Infect Dis 49:71–74.
    86.
    Gradel KO, Nielsen HL, Schonheyder HC, Ejlertsen T, Kristensen B, Nielsen H. 2009. Increased short- and long-term risk of inflammatory bowel disease after Salmonella or Campylobacter gastroenteritis. Gastroenterology 137:495–501.
    87.
    Zhang L, Man SM, Day AS, Leach ST, Lemberg DA, Dutt S, Stormon M, Otley A, O'Loughlin EV, Magoffin A, Ng PH, Mitchell H. 2009. Detection and isolation of Campylobacter species other than C. jejuni from children with Crohn's disease. J Clin Microbiol 47:453–455.
    88.
    Tankovic J, Burghoffer B, Petit JC. 2009. Frequent detection by real-time PCR of bacteria from the Helicobacter and Campylobacter genera in stool samples from inflammatory bowel disease patients, abstr R2084. Abstr 19th Eur Congr Clin Microbiol Infect Dis, Helsinki, Finland.
    89.
    Man SM, Zhang L, Day AS, Leach ST, Lemberg DA, Mitchell H. 2010. Campylobacter concisus and other Campylobacter species in children with newly diagnosed Crohn's disease. Inflamm Bowel Dis 16:1008–1016.
    90.
    Kaakoush NO, Day AS, Huinao KD, Leach ST, Lemberg DA, Dowd SE, Mitchell HM. 2012. Microbial dysbiosis in pediatric patients with Crohn's disease. J Clin Microbiol 50:3258–3266.
    91.
    Mahendran V, Riordan SM, Grimm MC, Tran TAT, Major J, Kaakoush NO, Mitchell H, Zhang L. 2011. Prevalence of Campylobacter species in adult Crohn's disease and the preferential colonization sites of Campylobacter species in the human intestine. PLoS One 6:e25417.
    92.
    Hansen R, Berry SH, Mukhopadhya I, Thomson JM, Saunders KA, Nicholl CE, Bisset WM, Loganathan S, Mahdi G, Kastner-Cole D, Barclay AR, Bishop J, Flynn DM, McGrogan P, Russell RK, El-Omar EM, Hold GL. 2013. The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: The BISCUIT Study. PLoS One 8:e58825.
    93.
    Mukhopadhya I, Thomson JM, Hansen R, Berry SH, El-Omar EM, Hold GL. 2011. Detection of Campylobacter concisus and other Campylobacter species in colonic biopsies from adults with ulcerative colitis. PLoS One 6:e21490.
    94.
    Rajilic-Stojanovic M, Shanahan F, Guarner F, de Vos WM. 2013. Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm Bowel Dis 19:481–488.
    95.
    Zhang L, Budiman V, Day AS, Mitchell H, Lemberg DA, Riordan SM, Grimm M, Leach ST, Ismail Y. 2010. Isolation and detection of Campylobacter concisus from saliva of healthy individuals and patients with inflammatory bowel disease. J Clin Microbiol 48:2965–2967.
    96.
    O'Brien CL, Pavli P, Gordon DM, Allison GE. 2014. Detection of bacterial DNA in lymph nodes of Crohn's disease patients using high throughput sequencing. Gut 63:1596–1606.
    97.
    Kovach Z, Kaakoush NO, Lamb S, Zhang L, Raftery MJ, Mitchell H. 2011. Immunoreactive proteins of Campylobacter concisus, an emergent intestinal pathogen. FEMS Immunol Med Microbiol 63:387–396.
    98.
    Kaakoush NO, Mitchell HM, Man SM. 2014. Role of emerging Campylobacter species in inflammatory bowel diseases. Inflamm Bowel Dis 20:2189–2197.
    99.
    Matsheka MI, Elisha BG, Lastovica AL, On SL. 2002. Genetic heterogeneity of Campylobacter concisus determined by pulsed field gel electrophoresis-based macrorestriction profiling. FEMS Microbiol Lett 211:17–22.
    100.
    Matsheka MI, Lastovica AJ, Zappe H, Elisha BG. 2006. The use of (GTG)5 oligonucleotide as an RAPD primer to type Campylobacter concisus. Lett Appl Microbiol 42:600–605.
    101.
    Aabenhus R, Permin H, On SL, Andersen LP. 2002. Prevalence of Campylobacter concisus in diarrhoea of immunocompromised patients. Scand J Infect Dis 34:248–252.
    102.
    Aabenhus R, On SL, Siemer BL, Permin H, Andersen LP. 2005. Delineation of Campylobacter concisus genomospecies by amplified fragment length polymorphism analysis and correlation of results with clinical data. J Clin Microbiol 43:5091–5096.
    103.
    Aabenhus R, Permin H, Andersen LP. 2005. Characterization and subgrouping of Campylobacter concisus strains using protein profiles, conventional biochemical testing and antibiotic susceptibility. Eur J Gastroenterol Hepatol 17:1019–1024.
    104.
    Engberg J, Bang DD, Aabenhus R, Aarestrup FM, Fussing V, Gerner-Smidt P. 2005. Campylobacter concisus: an evaluation of certain phenotypic and genotypic characteristics. Clin Microbiol Infect 11:288–295.
    105.
    On SL, Harrington CS. 2000. Identification of taxonomic and epidemiological relationships among Campylobacter species by numerical analysis of AFLP profiles. FEMS Microbiol Lett 193:161–169.
    106.
    Kaakoush NO, Castano-Rodriguez N, Day AS, Lemberg DA, Leach ST, Mitchell HM. 2014. Campylobacter concisus and exotoxin 9 levels in paediatric patients with Crohn's disease and their association with the intestinal microbiota. J Med Microbiol 63:99–105.
    107.
    Deshpande NP, Kaakoush NO, Wilkins MR, Mitchell HM. 2013. Comparative genomics of Campylobacter concisus isolates reveals genetic diversity and provides insights into disease association. BMC Genomics 14:585.
    108.
    Kaakoush NO, Deshpande NP, Wilkins MR, Tan CG, Burgos-Portugal JA, Raftery MJ, Day AS, Lemberg DA, Mitchell H. 2011. The pathogenic potential of Campylobacter concisus strains associated with chronic intestinal diseases. PLoS One 6:e29045.
    109.
    Kaakoush NO, Man SM, Lamb S, Raftery MJ, Wilkins MR, Kovach Z, Mitchell H. 2010. The secretome of Campylobacter concisus. FEBS J 277:1606–1617.
    110.
    Kaakoush NO, Castaño-Rodríguez N, Day AS, Lemberg DA, Leach ST, Mitchell HM. 2015. Faecal levels of zonula occludens toxin in paediatric patients with Crohn's disease and their association with the intestinal microbiota. J Med Microbiol 64:303–306.
    111.
    Man SM, Kaakoush NO, Leach ST, Nahidi L, Lu HK, Norman J, Day AS, Zhang L, Mitchell HM. 2010. Host attachment, invasion, and stimulation of proinflammatory cytokines by Campylobacter concisus and other non-Campylobacter jejuni Campylobacter species. J Infect Dis 202:1855–1865.
    112.
    Kaakoush NO, Deshpande NP, Man SM, Burgos-Portugal JA, Khattak FA, Raftery MJ, Wilkins MR, Mitchell HM. 2015. Transcriptomic and proteomic analyses reveal key innate immune signatures in the host response to the gastrointestinal pathogen Campylobacter concisus. Infect Immun 83:832–845.
    113.
    Macfarlane S, Furrie E, Macfarlane GT, Dillon JF. 2007. Microbial colonization of the upper gastrointestinal tract in patients with Barrett's esophagus. Clin Infect Dis 45:29–38.
    114.
    Pei Z, Bini EJ, Yang L, Zhou M, Francois F, Blaser MJ. 2004. Bacterial biota in the human distal esophagus. Proc Natl Acad Sci U S A 101:4250–4255.
    115.
    Pei Z, Yang L, Peek RM, Jr, Levine SM, Pride DT, Blaser MJ. 2005. Bacterial biota in reflux esophagitis and Barrett's esophagus. World J Gastroenterol 11:7277–7283.
    116.
    Yang L, Lu X, Nossa CW, Francois F, Peek RM, Pei Z. 2009. Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome. Gastroenterology 137:588–597.
    117.
    Liu N, Ando T, Ishiguro K, Maeda O, Watanabe O, Funasaka K, Nakamura M, Miyahara R, Ohmiya N, Goto H. 2013. Characterization of bacterial biota in the distal esophagus of Japanese patients with reflux esophagitis and Barrett's esophagus. BMC Infect Dis 13:130.
    118.
    Osias GL, Bromer MQ, Thomas RM, Friedel D, Miller LS, Suh B, Lorber B, Parkman HP, Fisher RS. 2004. Esophageal bacteria and Barrett's esophagus: a preliminary report. Dig Dis Sci 49:228–236.
    119.
    Blackett KL, Siddhi SS, Cleary S, Steed H, Miller MH, Macfarlane S, Macfarlane GT, Dillon JF. 2013. Oesophageal bacterial biofilm changes in gastro-oesophageal reflux disease, Barrett's and oesophageal carcinoma: association or causality? Aliment Pharmacol Ther 37:1084–1092.
    120.
    Palma G, Barbieri A, Bimonte S, Palla M, Zappavigna S, Caraglia M, Ascierto PA, Ciliberto G, Arra C. 2013. Interleukin 18: friend or foe in cancer. Biochim Biophys Acta 1836:296–303.
    121.
    Macuch PJ, Tanner AC. 2000. Campylobacter species in health, gingivitis, and periodontitis. J Dent Res 79:785–792.
    122.
    Kaakoush NO, Mitchell HM. 2012. Campylobacter concisus—a new player in intestinal disease. Front Cell Infect Microbiol 2:4.
    123.
    Etoh Y, Dewhirst FE, Paster BJ, Yamamoto A, Goto N. 1993. Campylobacter showae sp. nov., isolated from the human oral cavity. Int J Syst Bacteriol 43:631–639.
    124.
    Loesche WJ, Gibbons RJ, Socransky SS. 1965. Biochemical characteristics of Vibrio sputorum and relationship to Vibrio bubulus and Vibrio fetus. J Bacteriol 89:1109–1116.
    125.
    van Palenstein Helderman WH. 1975. Total viable count and differential count of Vibrio (Campylobacter) sputorum, Fusobacterium nucleatum, Selenomonas sputigena, Bacteroides ochraceus and Veillonella in the inflamed and noninflamed human gingival crevice. J Periodont Res 10:294–305.
    126.
    Duerden BI, Goodwin L, O'Neil TC. 1987. Identification of Bacteroides species from adult periodontal disease. J Med Microbiol 24:133–137.
    127.
    Tanner AC, Dzink JL, Ebersole JL, Socransky SS. 1987. Wolinella recta, Campylobacter concisus, Bacteroides gracilis, and Eikenella corrodens from periodontal lesions. J Periodont Res 22:327–330.
    128.
    Tanner ACR, Badger S, Lai CH, Listarten MA, Visconti RA, Socransky SS. 1981. Wolinella gen. nov., Wolinella succinogenes (Vibrio succinogenes Wolin et al.) comb. nov., and description of Bacteroides gracilis sp. nov., Wolinella recta sp. nov., Campylobacter concisus sp. nov., and Eikenella corrodens from humans with periodontal disease. Int J Syst Bacteriol 31:432–445.
    129.
    Henne K, Fuchs F, Kruth S, Horz HP, Conrads G. 2014. Shifts in Campylobacter species abundance may reflect general microbial community shifts in periodontitis progression. J Oral Microbiol 6:25874.
    130.
    Lee HJ, Kim JK, Cho JY, Lee JM, Hong SH. 2012. Quantification of subgingival bacterial pathogens at different stages of periodontal diseases. Curr Microbiol 65:22–27.
    131.
    Lopez R, Dahlen G, Retamales C, Baelum V. 2011. Clustering of subgingival microbial species in adolescents with periodontitis. Eur J Oral Sci 119:141–150.
    132.
    von Troil-Linden B, Torkko H, Alaluusua S, Jousimies-Somer H, Asikainen S. 1995. Salivary levels of suspected periodontal pathogens in relation to periodontal status and treatment. J Dent Res 74:1789–1795.
    133.
    Ihara H, Miura T, Kato T, Ishihara K, Nakagawa T, Yamada S, Okuda K. 2003. Detection of Campylobacter rectus in periodontitis sites by monoclonal antibodies. J Periodont Res 38:64–72.
    134.
    Tanner A, Maiden MF, Macuch PJ, Murray LL, Kent RL, Jr. 1998. Microbiota of health, gingivitis, and initial periodontitis. J Clin Periodontol 25:85–98.
    135.
    Aas JA, Griffen AL, Dardis SR, Lee AM, Olsen I, Dewhirst FE, Leys EJ, Paster BJ. 2008. Bacteria of dental caries in primary and permanent teeth in children and young adults. J Clin Microbiol 46:1407–1417.
    136.
    Johnson CC, Reinhardt JF, Edelstein MA, Mulligan ME, George WL, Finegold SM. 1985. Bacteroides gracilis, an important anaerobic bacterial pathogen. J Clin Microbiol 22:799–802.
    137.
    Rawlinson A, Eleys K, Bennett KW, Goodwin L. 1994. Bacteroides gracilis in periodontal health and disease. Microb Ecol Health Dis 7:201–205.
    138.
    Shen S, Samaranayake LP, Yip HK. 2005. Coaggregation profiles of the microflora from root surface caries lesions. Arch Oral Biol 50:23–32.
    139.
    Haririan H, Andrukhov O, Bertl K, Lettner S, Kierstein S, Moritz A, Rausch-Fan X. 2014. Microbial analysis of subgingival plaque samples compared to that of whole saliva in patients with periodontitis. J Periodontol 85:819–828.
    140.
    Moore WE, Holdeman LV, Cato EP, Smibert RM, Burmeister JA, Palcanis KG, Ranney RR. 1985. Comparative bacteriology of juvenile periodontitis. Infect Immun 48:507–519.
    141.
    Moore LV, Moore WE, Cato EP, Smibert RM, Burmeister JA, Best AM, Ranney RR. 1987. Bacteriology of human gingivitis. J Dent Res 66:989–995.
    142.
    Kamma JJ, Nakou M, Manti FA. 1994. Microbiota of rapidly progressive periodontitis lesions in association with clinical parameters. J Periodontol 65:1073–1078.
    143.
    Ebersole JL, Taubman MA, Smith DJ, Haffajee AD. 1985. Effect of subgingival scaling on systemic antibody responses to oral microorganisms. Infect Immun 48:534–539.
    144.
    Taubman MA, Haffajee AD, Socransky SS, Smith DJ, Ebersole JL. 1992. Longitudinal monitoring of humoral antibody in subjects with destructive periodontal diseases. J Periodont Res 27:511–521.
    145.
    Haffajee AD, Socransky SS, Ebersole JL, Smith DJ. 1984. Clinical, microbiological and immunological features associated with the treatment of active periodontosis lesions. J Clin Periodontol 11:600–618.
    146.
    Ercan E, Eratalay K, Deren O, Gur D, Ozyuncu O, Altun B, Kanli C, Ozdemir P, Akincibay H. 2013. Evaluation of periodontal pathogens in amniotic fluid and the role of periodontal disease in pre-term birth and low birth weight. Acta Odontol Scand 71:553–559.
    147.
    Brito F, Zaltman C, Carvalho AT, Fischer RG, Persson R, Gustafsson A, Figueredo CM. 2013. Subgingival microflora in inflammatory bowel disease patients with untreated periodontitis. Eur J Gastroenterol Hepatol 25:239–245.
    148.
    Ismail Y, Mahendran V, Octavia S, Day AS, Riordan SM, Grimm MC, Lan R, Lemberg D, Tran TA, Zhang L. 2012. Investigation of the enteric pathogenic potential of oral Campylobacter concisus strains isolated from patients with inflammatory bowel disease. PLoS One 7:e38217.
    149.
    Van Dyke TE, Dowell VR, Jr, Offenbacher S, Snyder W, Hersh T. 1986. Potential role of microorganisms isolated from periodontal lesions in the pathogenesis of inflammatory bowel disease. Infect Immun 53:671–677.
    150.
    Moss-Morris R, Spence M. 2006. To “lump” or to “split” the functional somatic syndromes: can infectious and emotional risk factors differentiate between the onset of chronic fatigue syndrome and irritable bowel syndrome? Psychosom Med 68:463–469.
    151.
    Neal KR, Hebden J, Spiller R. 1997. Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factors for development of the irritable bowel syndrome: postal survey of patients. BMJ 314:779–782.
    152.
    Dunlop SP, Jenkins D, Neal KR, Spiller RC. 2003. Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS. Gastroenterology 125:1651–1659.
    153.
    Stermer E, Lubezky A, Potasman I, Paster E, Lavy A. 2006. Is traveler's diarrhea a significant risk factor for the development of irritable bowel syndrome? A prospective study. Clin Infect Dis 43:898–901.
    154.
    Marshall JK, Thabane M, Garg AX, Clark WF, Salvadori M, Collins SM. 2006. Incidence and epidemiology of irritable bowel syndrome after a large waterborne outbreak of bacterial dysentery. Gastroenterology 131:445–450.
    155.
    Okhuysen PC, Jiang ZD, Carlin L, Forbes C, DuPont HL. 2004. Post-diarrhea chronic intestinal symptoms and irritable bowel syndrome in North American travelers to Mexico. Am J Gastroenterol 99:1774–1778.
    156.
    Saps M, Pensabene L, Di Martino L, Staiano A, Wechsler J, Zheng X, Di Lorenzo C. 2008. Post-infectious functional gastrointestinal disorders in children. J Pediatr 152:812–816, 816.e1.
    157.
    Futagami S, Itoh T, Sakamoto C. 2015. Systematic review with meta-analysis: post-infectious functional dyspepsia. Aliment Pharmacol Ther 41:177–188.
    158.
    Ford AC, Thabane M, Collins SM, Moayyedi P, Garg AX, Clark WF, Marshall JK. 2010. Prevalence of uninvestigated dyspepsia 8 years after a large waterborne outbreak of bacterial dysentery: a cohort study. Gastroenterology 138:1727–1736.
    159.
    Porter CK, Choi D, Cash B, Pimentel M, Murray J, May L, Riddle MS. 2013. Pathogen-specific risk of chronic gastrointestinal disorders following bacterial causes of foodborne illness. BMC Gastroenterol 13:46.
    160.
    Parry SD, Stansfield R, Jelley D, Gregory W, Phillips E, Barton JR, Welfare MR. 2003. Does bacterial gastroenteritis predispose people to functional gastrointestinal disorders? A prospective, community-based, case-control study. Am J Gastroenterol 98:1970–1975.
    161.
    Futagami S, Shindo T, Kawagoe T, Horie A, Shimpuku M, Gudis K, Iwakiri K, Itoh T, Sakamoto C. 2010. Migration of eosinophils and CCR2-/CD68-double positive cells into the duodenal mucosa of patients with postinfectious functional dyspepsia. Am J Gastroenterol 105:1835–1842.
    162.
    Drossman DA. 2006. The functional gastrointestinal disorders and the Rome III process. Gastroenterology 130:1377–1390.
    163.
    Spiller R, Garsed K. 2009. Postinfectious irritable bowel syndrome. Gastroenterology 136:1979–1988.
    164.
    Thornley JP, Jenkins D, Neal K, Wright T, Brough J, Spiller RC. 2001. Relationship of Campylobacter toxigenicity in vitro to the development of postinfectious irritable bowel syndrome. J Infect Dis 184:606–609.
    165.
    Marshall JK, Thabane M, Garg AX, Clark WF, Moayyedi P, Collins SM. 2010. Eight year prognosis of postinfectious irritable bowel syndrome following waterborne bacterial dysentery. Gut 59:605–611.
    166.
    Schwille-Kiuntke J, Enck P, Zendler C, Krieg M, Polster AV, Klosterhalfen S, Autenrieth IB, Zipfel S, Frick JS. 2011. Postinfectious irritable bowel syndrome: follow-up of a patient cohort of confirmed cases of bacterial infection with Salmonella or Campylobacter. Neurogastroenterol Motil 23:e479–e488.
    167.
    Grover M, Camilleri M, Smith K, Linden DR, Farrugia G. 2014. On the fiftieth anniversary. Postinfectious irritable bowel syndrome: mechanisms related to pathogens. Neurogastroenterol Motil 26:156–167.
    168.
    Nielsen HL, Engberg J, Ejlertsen T, Nielsen H. 2014. Psychometric scores and persistence of irritable bowel after Campylobacter concisus infection. Scand J Gastroenterol 49:545–551.
    169.
    Warren RL, Freeman DJ, Pleasance S, Watson P, Moore RA, Cochrane K, Allen-Vercoe E, Holt RA. 2013. Co-occurrence of anaerobic bacteria in colorectal carcinomas. Microbiome 1:16.
    170.
    Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, Ojesina AI, Jung J, Bass AJ, Tabernero J, Baselga J, Liu C, Shivdasani RA, Ogino S, Birren BW, Huttenhower C, Garrett WS, Meyerson M. 2012. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22:292–298.
    171.
    Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, Barnes R, Watson P, Allen-Vercoe E, Moore RA, Holt RA. 2012. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 22:299–306.
    172.
    Wu N, Yang X, Zhang R, Li J, Xiao X, Hu Y, Chen Y, Yang F, Lu N, Wang Z, Luan C, Liu Y, Wang B, Xiang C, Wang Y, Zhao F, Gao GF, Wang S, Li L, Zhang H, Zhu B. 2013. Dysbiosis signature of fecal microbiota in colorectal cancer patients. Microb Ecol 66:462–470.
    173.
    Riddle MS, Gutierrez RL, Verdu EF, Porter CK. 2012. The chronic gastrointestinal consequences associated with Campylobacter. Curr Gastroenterol Rep 14:395–405.
    174.
    Altobelli E, Paduano R, Petrocelli R, Di Orio F. 2014. Burden of celiac disease in Europe: a review of its childhood and adulthood prevalence and incidence as of September 2014. Ann Ig 26:485–498.
    175.
    Riddle MS, Murray JA, Porter CK. 2012. The incidence and risk of celiac disease in a healthy US adult population. Am J Gastroenterol 107:1248–1255.
    176.
    Verdu EF, Mauro M, Bourgeois J, Armstrong D. 2007. Clinical onset of celiac disease after an episode of Campylobacter jejuni enteritis. Can J Gastroenterol 21:453–455.
    177.
    Riddle MS, Murray JA, Cash BD, Pimentel M, Porter CK. 2013. Pathogen-specific risk of celiac disease following bacterial causes of foodborne illness: a retrospective cohort study. Dig Dis Sci 58:3242–3245.
    178.
    Vaughan-Shaw PG, Rees JR, White D, Burgess P. 2010. Campylobacter jejuni cholecystitis: a rare but significant clinical entity. BMJ Case Rep 2010:bcr1020092365.
    179.
    Landry O. 1859. Note sur la paralysie ascendante aigue. Gaz Hebd Med Chir 6:472–474, 486–488.
    180.
    van Doorn PA, Ruts L, Jacobs BC. 2008. Clinical features, pathogenesis, and treatment of Guillain-Barre syndrome. Lancet Neurol 7:939–950.
    181.
    Guillain G, Barré J, Strohl A. 1916. Sur un syndrome de radiculo-nevrite avec hyperalbuminose du liquide cephalorachidien sans reaction cellulaire. Remarques sur les caracteres cliniques et graphiques des reflexes tendineux. Bull Soc Med Hop Paris 28:1462–1470.
    182.
    Kuwabara S, Yuki N. 2013. Axonal Guillain-Barre syndrome: concepts and controversies. Lancet Neurol 12:1180–1188.
    183.
    Bae JS, Yuki N, Kuwabara S, Kim JK, Vucic S, Lin CS, Kiernan MC. 2014. Guillain-Barre syndrome in Asia. J Neurol Neurosurg Psychiatry 85:907–913.
    184.
    Baker MG, Kvalsvig A, Zhang J, Lake R, Sears A, Wilson N. 2012. Declining Guillain-Barre syndrome after campylobacteriosis control, New Zealand, 1988–2010. Emerg Infect Dis 18:226–233.
    185.
    Jackson BR, Zegarra JA, Lopez-Gatell H, Sejvar J, Arzate F, Waterman S, Nunez AS, Lopez B, Weiss J, Cruz RQ, Murrieta DY, Luna-Gierke R, Heiman K, Vieira AR, Fitzgerald C, Kwan P, Zarate-Bermudez M, Talkington D, Hill VR, Mahon B. 2014. Binational outbreak of Guillain-Barre syndrome associated with Campylobacter jejuni infection, Mexico and USA, 2011. Epidemiol Infect 142:1089–1099.
    186.
    Keithlin J, Sargeant J, Thomas MK, Fazil A. 2014. Systematic review and meta-analysis of the proportion of Campylobacter cases that develop chronic sequelae. BMC Public Health 14:1203.
    187.
    Freddo L, Yu RK, Latov N, Donofrio PD, Hays AP, Greenberg HS, Albers JW, Allessi AG, Keren D. 1986. Gangliosides GM1 and GD1b are antigens for IgM M-protein in a patient with motor neuron disease. Neurology 36:454–458.
    188.
    Bax M, Kuijf ML, Heikema AP, van Rijs W, Bruijns SC, Garcia-Vallejo JJ, Crocker PR, Jacobs BC, van Vliet SJ, van Kooyk Y. 2011. Campylobacter jejuni lipooligosaccharides modulate dendritic cell-mediated T cell polarization in a sialic acid linkage-dependent manner. Infect Immun 79:2681–2689.
    189.
    Heikema AP, Koning RI, Duarte Dos Santos Rico S, Rempel H, Jacobs BC, Endtz HP, van Wamel WJ, Samsom JN. 2013. Enhanced, sialoadhesin-dependent uptake of Guillain-Barre syndrome-associated Campylobacter jejuni strains by human macrophages. Infect Immun 81:2095–2103.
    190.
    Malik A, Sharma D, St Charles J, Dybas LA, Mansfield LS. 2014. Contrasting immune responses mediate Campylobacter jejuni-induced colitis and autoimmunity. Mucosal Immunol 7:802–817.
    191.
    Taboada EN, van Belkum A, Yuki N, Acedillo RR, Godschalk PC, Koga M, Endtz HP, Gilbert M, Nash JH. 2007. Comparative genomic analysis of Campylobacter jejuni associated with Guillain-Barre and Miller Fisher syndromes: neuropathogenic and enteritis-associated isolates can share high levels of genomic similarity. BMC Genomics 8:359.
    192.
    Fisher M. 1956. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J Med 255:57–65.
    193.
    Chiba A, Kusunoki S, Shimizu T, Kanazawa I. 1992. Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome. Ann Neurol 31:677–679.
    194.
    Koga M, Gilbert M, Li J, Koike S, Takahashi M, Furukawa K, Hirata K, Yuki N. 2005. Antecedent infections in Fisher syndrome: a common pathogenesis of molecular mimicry. Neurology 64:1605–1611.
    195.
    Heikema AP, Jacobs BC, Horst-Kreft D, Huizinga R, Kuijf ML, Endtz HP, Samsom JN, van Wamel WJ. 2013. Siglec-7 specifically recognizes Campylobacter jejuni strains associated with oculomotor weakness in Guillain-Barre syndrome and Miller Fisher syndrome. Clin Microbiol Infect 19:E106–E112.
    196.
    Lee KY. 2012. Anti-GQ1b-negative Miller Fisher syndrome after Campylobacter jejuni enteritis. Pediatr Neurol 47:213–215.
    197.
    Koga M, Gilbert M, Takahashi M, Li J, Hirata K, Kanda T, Yuki N. 2012. GQ1b-seronegative Fisher syndrome: clinical features and new serological markers. J Neurol 259:1366–1374.
    198.
    Oyazato Y, Shiihara T, Kusunoki S, Adachi M, Ohnishi N, Taniguchi H, Nishiyama A, Watanabe A, Kobayashi M, Kamioka I. 2012. A case of anti-GA1 antibody-positive Fisher syndrome with elevated tau protein in cerebrospinal fluid. Brain Dev 34:329–332.
    199.
    Tauxe RV, Patton CM, Edmonds P, Barrett TJ, Brenner DJ, Blake PA. 1985. Illness associated with Campylobacter laridis, a newly recognized Campylobacter species. J Clin Microbiol 21:222–225.
    200.
    Chua K, Gurtler V, Montgomery J, Fraenkel M, Mayall BC, Grayson ML. 2007. Campylobacter insulaenigrae causing septicaemia and enteritis. J Med Microbiol 56:1565–1567.
    201.
    Louwen R, Baarlen P, Vliet AH, Belkum A, Hays JP, Endtz HP. 2012. Campylobacter bacteremia: a rare and under-reported event? Eur J Microbiol Immunol 2:76–87.
    202.
    Pigrau C, Bartolome R, Almirante B, Planes AM, Gavalda J, Pahissa A. 1997. Bacteremia due to Campylobacter species: clinical findings and antimicrobial susceptibility patterns. Clin Infect Dis 25:1414–1420.
    203.
    Pacanowski J, Lalande V, Lacombe K, Boudraa C, Lesprit P, Legrand P, Trystram D, Kassis N, Arlet G, Mainardi JL, Doucet-Populaire F, Girard PM, Meynard JL. 2008. Campylobacter bacteremia: clinical features and factors associated with fatal outcome. Clin Infect Dis 47:790–796.
    204.
    Liao CH, Chuang CY, Huang YT, Lee PI, Hsueh PR. 2012. Bacteremia caused by antimicrobial resistant Campylobacter species at a medical center in Taiwan, 1998–2008. J Infect 65:392–399.
    205.
    Nielsen H, Hansen KK, Gradel KO, Kristensen B, Ejlertsen T, Ostergaard C, Schonheyder HC. 2010. Bacteraemia as a result of Campylobacter species: a population-based study of epidemiology and clinical risk factors. Clin Microbiol Infect 16:57–61.
    206.
    Feodoroff B, Lauhio A, Ellstrom P, Rautelin H. 2011. A nationwide study of Campylobacter jejuni and Campylobacter coli bacteremia in Finland over a 10-year period, 1998–2007, with special reference to clinical characteristics and antimicrobial susceptibility. Clin Infect Dis 53:e99–e106.
    207.
    Ben-Shimol S, Carmi A, Greenberg D. 2013. Demographic and clinical characteristics of Campylobacter bacteremia in children with and without predisposing factors. Pediatr Infect Dis J 32:e414–e418.
    208.
    Blaser MJ, Perez GP, Smith PF, Patton C, Tenover FC, Lastovica AJ, Wang WI. 1986. Extraintestinal Campylobacter jejuni and Campylobacter coli infections: host factors and strain characteristics. J Infect Dis 153:552–559.
    209.
    Nagy MT, Hla SM. 2013. Campylobacter fetus sepsis in an immunocompetent patient with haematological complication. BMJ Case Rep 2013:bcr2013008610.
    210.
    Chusid MJ, Wortmann DW, Dunne WM. 1990. “Campylobacter upsaliensis” sepsis in a boy with acquired hypogammaglobulinemia. Diagn Microbiol Infect Dis 13:367–369.
    211.
    Fujihara N, Takakura S, Saito T, Iinuma Y, Ichiyama S. 2006. A case of perinatal sepsis by Campylobacter fetus subsp. fetus infection successfully treated with carbapenem—case report and literature review. J Infect 53:e199–e202.
    212.
    Becker S, Ejlertsen T, Kristensen B, Norgaard M, Nielsen H. 2007. Is the incidence of perimyocarditis increased following Campylobacter jejuni infection? Eur J Clin Microbiol Infect Dis 26:927–929.
    213.
    Florkowski CM, Ikram RB, Crozier IM, Ikram H, Berry ME. 1984. Campylobacter jejuni myocarditis. Clin Cardiol 7:558–559.
    214.
    Cox ID, Fluck DS, Joy MD. 2001. Campylobacter myocarditis; loose bowels and a baggy heart. Eur J Heart Fail 3:105–107.
    215.
    Westling K, Evengard B. 2001. Myocarditis associated with Campylobacter infection. Scand J Infect Dis 33:877–878.
    216.
    Cunningham C, Lee CH. 2003. Myocarditis related to Campylobacter jejuni infection: a case report. BMC Infect Dis 3:16.
    217.
    Reda E, Mansell C. 2005. Myocarditis in a patient with Campylobacter infection. N Z Med J 118:U1634.
    218.
    Mera V, Lopez T, Serralta J. 2007. Take traveller's diarrhoea to heart. Travel Med Infect Dis 5:202–203.
    219.
    Pena LA, Fishbein MC. 2007. Fatal myocarditis related to Campylobacter jejuni infection: a case report. Cardiovasc Pathol 16:119–121.
    220.
    Braun KP, Theissig F, Ernst H, May M, Krulls-Munch J. 2008. Campylobacter jejuni-associated hepatitis and myocardial injury. Med Klin (Munich) 103:346–348.
    221.
    Turley AJ, Crilley JG, Hall JA. 2008. Acute myocarditis secondary to Campylobacter jejuni enterocolitis. Resuscitation 79:165–167.
    222.
    Kratzer C, Wolf F, Graninger W, Weissel M. 2010. Acute cardiac disease in a young patient with Campylobacter jejuni infection: a case report. Wien Klin Wochenschr 122:315–319.
    223.
    Ponka A, Pitkanen T, Pettersson T, Aittoniemi S, Kosunen TU. 1980. Carditis and arthritis associated with Campylobacter jejuni infection. Acta Med Scand 208:495–496.
    224.
    Hull SR, Varma MP. 2011. Myopericarditis following Campylobacter infection. Ir J Med Sci 180:753–755.
    225.
    Alzand BS, Ilhan M, Heesen WF, Meeder JG. 2010. Campylobacter jejuni: enterocolitis and myopericarditis. Int J Cardiol 144:e14–e16.
    226.
    Panikkath R, Costilla V, Hoang P, Wood J, Gruden JF, Dietrich B, Gotway MB, Appleton C. 2014. Chest pain and diarrhea: a case of Campylobacter jejuni-associated myocarditis. J Emerg Med 46:180–183.
    227.
    Murphy D, Jolly C, MacDonald S, Troughton R. 2013. Myocarditis associated with Campylobacter jejuni. N Z Med J 126:95–98.
    228.
    De Cock D, Hiltrop N, Timmermans P, Dymarkowski S, Van Cleemput J. 2012. Myocarditis associated with Campylobacter enteritis: report of three cases. Circ Heart Fail 5:e19–e21.
    229.
    Kotilainen P, Lehtopolku M, Hakanen AJ. 2006. Myopericarditis in a patient with Campylobacter enteritis: a case report and literature review. Scand J Infect Dis 38:549–552.
    230.
    Hannu T, Mattila L, Rautelin H, Siitonen A, Leirisalo-Repo M. 2005. Three cases of cardiac complications associated with Campylobacter jejuni infection and review of the literature. Eur J Clin Microbiol Infect Dis 24:619–622.
    231.
    Abbass K, Emig M, Bernstein JM. 2011. Sepsis and pericarditis caused by Campylobacter fetus: case report and literature review. J Ark Med Soc 108:88–89.
    232.
    Uzoigwe C. 2005. Campylobacter infections of the pericardium and myocardium. Clin Microbiol Infect 11:253–255.
    233.
    Farrugia DC, Eykyn SJ, Smyth EG. 1994. Campylobacter fetus endocarditis: two case reports and review. Clin Infect Dis 18:443–446.
    234.
    Dinant S, Schurink CA, Deckers JW, Severin JA. 2011. Aortic homograft endocarditis caused by Campylobacter jejuni. J Clin Microbiol 49:4016–4017.
    235.
    Haruyama A, Toyoda S, Kikuchi M, Arikawa T, Inami S, Otani N, Amano H, Matsuda R, Inoue T. 2011. Campylobacter fetus as cause of prosthetic valve endocarditis. Tex Heart Inst J 38:584–587.
    236.
    Caramelli B, Mansur AJ, Grinberg M, Mendes CM, Pileggi F. 1988. Campylobacter fetus endocarditis on a prosthetic heart valve. South Med J 81:802–803.
    237.
    Peetermans WE, De Man F, Moerman P, van de Werf F. 2000. Fatal prosthetic valve endocarditis due to Campylobacter fetus. J Infect 41:180–182.
    238.
    Morrison VA, Lloyd BK, Chia JK, Tuazon CU. 1990. Cardiovascular and bacteremic manifestations of Campylobacter fetus infection: case report and review. Rev Infect Dis 12:387–392.
    239.
    Prendki V, Marmor S, Zeller V, Lhotellier L, Megraud F, Desplaces N. 2013. Campylobacter infection after prosthetic joint surgery. Scand J Infect Dis 45:706–710.
    240.
    Kell RJA, Ellis ME. 1985. Transient atrial fibrillation in Campylobacter jejuni infection. BMJ 291:1542.
    241.
    Bucknell SJ, Le T, Amerena J, Hill DG, McDonald M. 2000. Aortic dissection associated with Campylobacter aortitis. Heart Lung Circ 9:88–91.
    242.
    Abassade P, Cremieux O, Korach JM, Templier F, Morette C, Wolff M, Baudouy PY, Farge C. 1994. Campylobacter fetus subspecies fetus endoaortitis on a Bentall tube prosthesis. Apropos of a case. Arch Mal Coeur Vaiss 87:1483–1487.
    243.
    Blabey RG, Jr, Parry MF, Bull SM, Weed CB. 1983. Mycotic aneurysm of the abdominal aorta: successful management of Campylobacter fetus aortitis. Conn Med 47:129–130.
    244.
    Gazaigne L, Legrand P, Renaud B, Bourra B, Taillandier E, Brun-Buisson C, Lesprit P. 2008. Campylobacter fetus bloodstream infection: risk factors and clinical features. Eur J Clin Microbiol Infect Dis 27:185–189.
    245.
    Thomas K, Chan KN, Ribeiro CD. 1980. Campylobacter jejuni/coli meningitis in a neonate. Br Med J 280:1301–1302.
    246.
    Goossens H, Henocque G, Kremp L, Rocque J, Boury R, Alanio G, Vlaes L, Hemelhof W, Van den Borre C, Macart M, et al. 1986. Nosocomial outbreak of Campylobacter jejuni meningitis in newborn infants. Lancet ii:146–149.
    247.
    Ruef C, Fah L, Caduff F. 1988. Campylobacter jejuni: sepsis and meningitis in an adult without risk factors. Schweiz Med Wochenschr 118:302–304.
    248.
    Dronda F, Garcia-Arata I, Navas E, de Rafael L. 1998. Meningitis in adults due to Campylobacter fetus subspecies fetus. Clin Infect Dis 27:906–907.
    249.
    Burch KL, Saeed K, Sails AD, Wright PA. 1999. Successful treatment by meropenem of Campylobacter jejuni meningitis in a chronic alcoholic following neurosurgery. J Infect 39:241–243.
    250.
    Umehara Y, Kudo M, Kawasaki M. 2009. Campylobacter fetus meningitis in a patient with Crohn's disease. Inflamm Bowel Dis 15:645–646.
    251.
    Kogawa S, Furukawa K. 2010. Campylobacter jejuni meningitis in an immunocompetent adult male. Rinsho Shinkeigaku 50:262–264.
    252.
    Tsoni K, Papadopoulou E, Michailidou E, Kavaliotis I. 2013. Campylobacter jejuni meningitis in a neonate: a rare case report. J Neonatal Perinatal Med 6:183–185.
    253.
    Spiegel CA, Telford G. 1984. Isolation of Wolinella recta and Actinomyces viscosus from an actinomycotic chest wall mass. J Clin Microbiol 20:1187–1189.
    254.
    Han XY, Tarrand JJ, Rice DC. 2005. Oral Campylobacter species involved in extraoral abscess: a report of three cases. J Clin Microbiol 43:2513–2515.
    255.
    de Vries JJ, Arents NL, Manson WL. 2008. Campylobacter species isolated from extra-oro-intestinal abscesses: a report of four cases and literature review. Eur J Clin Microbiol Infect Dis 27:1119–1123.
    256.
    Batz MB, Henke E, Kowalcyk B. 2013. Long-term consequences of foodborne infections. Infect Dis Clin North Am 27:599–616.
    257.
    Pope JE, Krizova A, Garg AX, Thiessen-Philbrook H, Ouimet JM. 2007. Campylobacter reactive arthritis: a systematic review. Semin Arthritis Rheum 37:48–55.
    258.
    Ajene AN, Fischer Walker CL, Black RE. 2013. Enteric pathogens and reactive arthritis: a systematic review of Campylobacter, Salmonella and Shigella-associated reactive arthritis. J Health Popul Nutr 31:299–307.
    259.
    Simor AE, Karmali MA, Jadavji T, Roscoe M. 1986. Abortion and perinatal sepsis associated with Campylobacter infection. Rev Infect Dis 8:397–402.
    260.
    Gurgan T, Diker KS. 1994. Abortion associated with Campylobacter upsaliensis. J Clin Microbiol 32:3093–3094.
    261.
    Mendz GL, Petersen R, Quinlivan JA, Kaakoush NO. 2014. Potential involvement of Campylobacter curvus and Haemophilus parainfluenzae in preterm birth. BMJ Case Rep 2014:bcr2014205282.
    262.
    Arce RM, Barros SP, Wacker B, Peters B, Moss K, Offenbacher S. 2009. Increased TLR4 expression in murine placentas after oral infection with periodontal pathogens. Placenta 30:156–162.
    263.
    Arce RM, Caron KM, Barros SP, Offenbacher S. 2012. Toll-like receptor 4 mediates intrauterine growth restriction after systemic Campylobacter rectus infection in mice. Mol Oral Microbiol 27:373–381.
    264.
    Lastovica AJ, le Roux E. 2000. Efficient isolation of campylobacteria from stools. J Clin Microbiol 38:2798–2799.
    265.
    Kim SA, Lee YM, Hwang IG, Kang DH, Woo GJ, Rhee MS. 2009. Eight enrichment broths for the isolation of Campylobacter jejuni from inoculated suspensions and ground pork. Lett Appl Microbiol 49:620–626.
    266.
    Iwamoto M, Huang JY, Cronquist AB, Medus C, Hurd S, Zansky S, Dunn J, Woron AM, Oosmanally N, Griffin PM, Besser J, Henao OL. 2015. Bacterial enteric infections detected by culture-independent diagnostic tests—FoodNet, United States, 2012–2014. MMWR Morb Mortal Wkly Rep 64:252–257.
    267.
    Kulkarni SP, Lever S, Logan JM, Lawson AJ, Stanley J, Shafi MS. 2002. Detection of Campylobacter species: a comparison of culture and polymerase chain reaction based methods. J Clin Pathol 55:749–753.
    268.
    Maher M, Finnegan C, Collins E, Ward B, Carroll C, Cormican M. 2003. Evaluation of culture methods and a DNA probe-based PCR assay for detection of Campylobacter species in clinical specimens of feces. J Clin Microbiol 41:2980–2986.
    269.
    On SL. 2001. Taxonomy of Campylobacter, Arcobacter, Helicobacter and related bacteria: current status, future prospects and immediate concerns. Symp Ser Soc Appl Microbiol 2001:1S–15S.
    270.
    Man SM, Kaakoush NO, Octavia S, Mitchell H. 2010. The internal transcribed spacer region, a new tool for use in species differentiation and delineation of systematic relationships within the Campylobacter genus. Appl Environ Microbiol 76:3071–3081.
    271.
    Eyers M, Chapelle S, Van Camp G, Goossens H, De Wachter R. 1993. Discrimination among thermophilic Campylobacter species by polymerase chain reaction amplification of 23S rRNA gene fragments. J Clin Microbiol 31:3340–3343.
    272.
    Fermer C, Engvall EO. 1999. Specific PCR identification and differentiation of the thermophilic campylobacters, Campylobacter jejuni, C. coli, C. lari, and C. upsaliensis. J Clin Microbiol 37:3370–3373.
    273.
    Christensen H, Jorgensen K, Olsen JE. 1999. Differentiation of Campylobacter coli and C. jejuni by length and DNA sequence of the 16S-23S rRNA internal spacer region. Microbiology 145:99–105.
    274.
    Hurtado A, Owen RJ. 1997. A molecular scheme based on 23S rRNA gene polymorphisms for rapid identification of Campylobacter and Arcobacter species. J Clin Microbiol 35:2401–2404.
    275.
    Granato PA, Chen L, Holiday I, Rawling RA, Novak-Weekley SM, Quinlan T, Musser KA. 2010. Comparison of premier CAMPY enzyme immunoassay (EIA), ProSpecT Campylobacter EIA, and ImmunoCard STAT! CAMPY tests with culture for laboratory diagnosis of Campylobacter enteric infections. J Clin Microbiol 48:4022–4027.
    276.
    Javed MA, Poshtiban S, Arutyunov D, Evoy S, Szymanski CM. 2013. Bacteriophage receptor binding protein based assays for the simultaneous detection of Campylobacter jejuni and Campylobacter coli. PLoS One 8:e69770.
    277.
    Allos BM. 2001. Campylobacter jejuni infections: update on emerging issues and trends. Clin Infect Dis 32:1201–1206.
    278.
    Smith JL, Fratamico PM. 2010. Fluoroquinolone resistance in Campylobacter. J Food Prot 73:1141–1152.
    279.
    Luangtongkum T, Jeon B, Han J, Plummer P, Logue CM, Zhang Q. 2009. Antibiotic resistance in Campylobacter: emergence, transmission and persistence. Future Microbiol 4:189–200.
    280.
    Graham JP, Boland JJ, Silbergeld E. 2007. Growth promoting antibiotics in food animal production: an economic analysis. Public Health Rep 122:79–87.
    281.
    Tribble DR, Sanders JW, Pang LW, Mason C, Pitarangsi C, Baqar S, Armstrong A, Hshieh P, Fox A, Maley EA, Lebron C, Faix DJ, Lawler JV, Nayak G, Lewis M, Bodhidatta L, Scott DA. 2007. Traveler's diarrhea in Thailand: randomized, double-blind trial comparing single-dose and 3-day azithromycin-based regimens with a 3-day levofloxacin regimen. Clin Infect Dis 44:338–346.
    282.
    Vukelic D, Trkulja V, Salkovic-Petrisic M. 2010. Single oral dose of azithromycin versus 5 days of oral erythromycin or no antibiotic in treatment of Campylobacter enterocolitis in children: a prospective randomized assessor-blind study. J Pediatr Gastroenterol Nutr 50:404–410.
    283.
    McEwen SA, Fedorka-Cray PJ. 2002. Antimicrobial use and resistance in animals. Clin Infect Dis 34(Suppl 3):S93–S106.
    284.
    Wieczorek K, Osek J. 2013. Antimicrobial resistance mechanisms among Campylobacter. Biomed Res Int 2013:340605.
    285.
    Garin B, Gouali M, Wouafo M, Perchec AM, Pham MT, Ravaonindrina N, Urbes F, Gay M, Diawara A, Leclercq A, Rocourt J, Pouillot R. 2012. Prevalence, quantification and antimicrobial resistance of Campylobacter spp. on chicken neck-skins at points of slaughter in 5 major cities located on 4 continents. Int J Food Microbiol 157:102–107.
    286.
    Hakanen AJ, Lehtopolku M, Siitonen A, Huovinen P, Kotilainen P. 2003. Multidrug resistance in Campylobacter jejuni strains collected from Finnish patients during 1995–2000. J Antimicrob Chemother 52:1035–1039.
    287.
    Qin SS, Wu CM, Wang Y, Jeon B, Shen ZQ, Zhang Q, Shen JZ. 2011. Antimicrobial resistance in Campylobacter coli isolated from pigs in two provinces of China. Int J Food Microbiol 146:94–98.
    288.
    Nelson JM, Smith KE, Vugia DJ, Rabatsky-Ehr T, Segler SD, Kassenborg HD, Zansky SM, Joyce K, Marano N, Hoekstra RM, Angulo FJ. 2004. Prolonged diarrhea due to ciprofloxacin-resistant Campylobacter infection. J Infect Dis 190:1150–1157.
    289.
    Helms M, Simonsen J, Olsen KE, Molbak K. 2005. Adverse health events associated with antimicrobial drug resistance in Campylobacter species: a registry-based cohort study. J Infect Dis 191:1050–1055.
    290.
    Quinn T, Bolla JM, Pages JM, Fanning S. 2007. Antibiotic-resistant Campylobacter: could efflux pump inhibitors control infection? J Antimicrob Chemother 59:1230–1236.
    291.
    Qin S, Wang Y, Zhang Q, Chen X, Shen Z, Deng F, Wu C, Shen J. 2012. Identification of a novel genomic island conferring resistance to multiple aminoglycoside antibiotics in Campylobacter coli. Antimicrob Agents Chemother 56:5332–5339.
    292.
    Moore JE, Barton MD, Blair IS, Corcoran D, Dooley JS, Fanning S, Kempf I, Lastovica AJ, Lowery CJ, Matsuda M, McDowell DA, McMahon A, Millar BC, Rao JR, Rooney PJ, Seal BS, Snelling WJ, Tolba O. 2006. The epidemiology of antibiotic resistance in Campylobacter. Microbes Infect 8:1955–1966.
    293.
    Domingues AR, Pires SM, Halasa T, Hald T. 2012. Source attribution of human campylobacteriosis using a meta-analysis of case-control studies of sporadic infections. Epidemiol Infect 140:970–981.
    294.
    Swaminathan A, Torresi J, Schlagenhauf P, Thursky K, Wilder-Smith A, Connor BA, Schwartz E, Vonsonnenberg F, Keystone J, O'Brien DP. 2009. A global study of pathogens and host risk factors associated with infectious gastrointestinal disease in returned international travellers. J Infect 59:19–27.
    295.
    Ravel A, Nesbitt A, Marshall B, Sittler N, Pollari F. 2011. Description and burden of travel-related cases caused by enteropathogens reported in a Canadian community. J Travel Med 18:8–19.
    296.
    Ricotta EE, Palmer A, Wymore K, Clogher P, Oosmanally N, Robinson T, Lathrop S, Karr J, Hatch J, Dunn J, Ryan P, Blythe D. 2014. Epidemiology and antimicrobial resistance of international travel-associated Campylobacter infections in the United States, 2005–2011. Am J Public Health 104:e108–e114.
    297.
    Zinszer K, Michel P, Hardardottir H, Kristinsson KG, Sigmundsdottir G, St-Onge L, Reiersen J, Charland K, Lowman R. 2010. The impact of domestic travel on estimating regional rates of human campylobacteriosis. Epidemiol Infect 138:1735–1743.
    298.
    Gautret P, Cramer JP, Field V, Caumes E, Jensenius M, Gkrania-Klotsas E, de Vries PJ, Grobusch MP, Lopez-Velez R, Castelli F, Schlagenhauf P, Hervius Askling H, von Sonnenburg F, Lalloo DG, Loutan L, Rapp C, Basto F, Santos O'Connor F, Weld L, Parola P. 2012. Infectious diseases among travellers and migrants in Europe, EuroTravNet 2010. Euro Surveill 17:20205. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20205.
    299.
    Zenner D, Gillespie I. 2011. Travel-associated Salmonella and Campylobacter gastroenteritis in England: estimation of under-ascertainment through national laboratory surveillance. J Travel Med 18:414–417.
    300.
    Mughini-Gras L, Smid JH, Wagenaar JA, De Boer A, Havelaar AH, Friesema IH, French NP, Graziani C, Busani L, Van Pelt W. 2014. Campylobacteriosis in returning travellers and potential secondary transmission of exotic strains. Epidemiol Infect 142:1277–1288.
    301.
    Kapperud G, Skjerve E, Bean NH, Ostroff SM, Lassen J. 1992. Risk factors for sporadic Campylobacter infections: results of a case-control study in southeastern Norway. J Clin Microbiol 30:3117–3121.
    302.
    Neimann J, Engberg J, Molbak K, Wegener HC. 2003. A case-control study of risk factors for sporadic Campylobacter infections in Denmark. Epidemiol Infect 130:353–366.
    303.
    Greig JD, Ravel A. 2009. Analysis of foodborne outbreak data reported internationally for source attribution. Int J Food Microbiol 130:77–87.
    304.
    Pires SM, Vigre H, Makela P, Hald T. 2010. Using outbreak data for source attribution of human salmonellosis and campylobacteriosis in Europe. Foodborne Pathog Dis 7:1351–1361.
    305.
    Strachan NJ, Gormley FJ, Rotariu O, Ogden ID, Miller G, Dunn GM, Sheppard SK, Dallas JF, Reid TM, Howie H, Maiden MC, Forbes KJ. 2009. Attribution of Campylobacter infections in northeast Scotland to specific sources by use of multilocus sequence typing. J Infect Dis 199:1205–1208.
    306.
    Sheppard SK, Colles F, Richardson J, Cody AJ, Elson R, Lawson A, Brick G, Meldrum R, Little CL, Owen RJ, Maiden MC, McCarthy ND. 2010. Host association of Campylobacter genotypes transcends geographic variation. Appl Environ Microbiol 76:5269–5277.
    307.
    Strachan NJ, MacRae M, Thomson A, Rotariu O, Ogden ID, Forbes KJ. 2012. Source attribution, prevalence and enumeration of Campylobacter spp. from retail liver. Int J Food Microbiol 153:234–236.
    308.
    Mughini Gras L, Smid JH, Wagenaar JA, de Boer AG, Havelaar AH, Friesema IH, French NP, Busani L, van Pelt W. 2012. Risk factors for campylobacteriosis of chicken, ruminant, and environmental origin: a combined case-control and source attribution analysis. PLoS One 7:e42599.
    309.
    Ragimbeau C, Colin S, Devaux A, Decruyenaere F, Cauchie HM, Losch S, Penny C, Mossong J. 2014. Investigating the host specificity of Campylobacter jejuni and Campylobacter coli by sequencing gyrase subunit A. BMC Microbiol 14:205.
    310.
    Baily JL, Meric G, Bayliss S, Foster G, Moss SE, Watson E, Pascoe B, Mikhail J, Pizzi R, Goldstone RJ, Smith DG, Willoughby K, Hall AJ, Sheppard SK, Dagleish MP. 2015. Evidence of land-sea transfer of the zoonotic pathogen Campylobacter to a wildlife marine sentinel species. Mol Ecol 24:208–221.
    311.
    Kownhar H, Shankar EM, Rajan R, Vengatesan A, Rao UA. 2007. Prevalence of Campylobacter jejuni and enteric bacterial pathogens among hospitalized HIV infected versus non-HIV infected patients with diarrhoea in southern India. Scand J Infect Dis 39:862–866.
    312.
    Larsen IK, Gradel KO, Helms M, Hornstrup MK, Jurgens G, Mens H, Rosager CL, Clausen TH, Kronborg G, Nielsen H. 2011. Non-typhoidal Salmonella and Campylobacter infections among HIV-positive patients in Denmark. Scand J Infect Dis 43:3–7.
    313.
    Skirrow MB. 1977. Campylobacter enteritis: a “new” disease. Br Med J 2:9–11.
    314.
    Ellis-Iversen J, Ridley A, Morris V, Sowa A, Harris J, Atterbury R, Sparks N, Allen V. 2012. Persistent environmental reservoirs on farms as risk factors for Campylobacter in commercial poultry. Epidemiol Infect 140:916–924.
    315.
    Gu W, Siletzky RM, Wright S, Islam M, Kathariou S. 2009. Antimicrobial susceptibility profiles and strain type diversity of Campylobacter jejuni isolates from turkeys in eastern North Carolina. Appl Environ Microbiol 75:474–482.
    316.
    Giacomelli M, Andrighetto C, Lombardi A, Martini M, Piccirillo A. 2012. A longitudinal study on thermophilic Campylobacter spp. in commercial turkey flocks in northern Italy: occurrence and genetic diversity. Avian Dis 56:693–700.
    317.
    Colles FM, Ali JS, Sheppard SK, McCarthy ND, Maiden MC. 2011. Campylobacter populations in wild and domesticated mallard ducks (Anas platyrhynchos). Environ Microbiol Rep 3:574–580.
    318.
    Tresierra-Ayala A, Bendayan ME, Bernuy A, Pereyra G, Fernandez H. 1994. Chicken as potential contamination source of Campylobacter lari in Iquitos, Peru. Rev Inst Med Trop Sao Paulo 36:497–499.
    319.
    Kaakoush NO, Sodhi N, Chenu JW, Cox JM, Riordan SM, Mitchell HM. 2014. The interplay between Campylobacter and Helicobacter species and other gastrointestinal microbiota of commercial broiler chickens. Gut Pathog 6:18.
    320.
    Boysen L, Rosenquist H, Larsson JT, Nielsen EM, Sorensen G, Nordentoft S, Hald T. 2014. Source attribution of human campylobacteriosis in Denmark. Epidemiol Infect 142:1599–1608.
    321.
    Kittl S, Heckel G, Korczak BM, Kuhnert P. 2013. Source attribution of human Campylobacter isolates by MLST and fla-typing and association of genotypes with quinolone resistance. PLoS One 8:e81796.
    322.
    Wei W, Schupbach G, Held L. 2014. Time-series analysis of Campylobacter incidence in Switzerland. Epidemiol Infect 2014:1–8.
    323.
    Byrd JA, Corrier DE, Hume ME, Bailey RH, Stanker LH, Hargis BM. 1998. Incidence of Campylobacter in crops of preharvest market-age broiler chickens. Poult Sci 77:1303–1305.
    324.
    Ahmed MF, Schulz J, Hartung J. 2013. Survival of Campylobacter jejuni in naturally and artificially contaminated laying hen feces. Poult Sci 92:364–369.
    325.
    Food Standards Agency. 2014, posting date. A microbiological survey of Campylobacter contamination in fresh whole UK-produced chilled chickens at retail sale—interim report to cover quarters 1–3. Food Standards Agency, London, United Kingdom.
    326.
    Deckert AE, Taboada E, Mutschall S, Poljak Z, Reid-Smith RJ, Tamblyn S, Morrell L, Seliske P, Jamieson FB, Irwin R, Dewey CE, Boerlin P, McEwen SA. 2014. Molecular epidemiology of Campylobacter jejuni human and chicken isolates from two health units. Foodborne Pathog Dis 11:150–155.
    327.
    Levesque S, Fournier E, Carrier N, Frost E, Arbeit RD, Michaud S. 2013. Campylobacteriosis in urban versus rural areas: a case-case study integrated with molecular typing to validate risk factors and to attribute sources of infection. PLoS One 8:e83731.
    328.
    Rosenquist H, Boysen L, Krogh AL, Jensen AN, Nauta M. 2013. Campylobacter contamination and the relative risk of illness from organic broiler meat in comparison with conventional broiler meat. Int J Food Microbiol 162:226–230.
    329.
    Blaser MJ, LaForce FM, Wilson NA, Wang WL. 1980. Reservoirs for human campylobacteriosis. J Infect Dis 141:665–669.
    330.
    Moore JE, Wilson TS, Wareing DR, Humphrey TJ, Murphy PG. 2002. Prevalence of thermophilic Campylobacter spp. in ready-to-eat foods and raw poultry in northern Ireland. J Food Prot 65:1326–1328.
    331.
    Levallois P, Chevalier P, Gingras S, Dery P, Payment P, Michel P, Rodriguez M. 2014. Risk of infectious gastroenteritis in young children living in Quebec rural areas with intensive animal farming: results of a case-control study (2004–2007). Zoonoses Public Health 61:28–38.
    332.
    de Perio MA, Niemeier RT, Levine SJ, Gruszynski K, Gibbins JD. 2013. Campylobacter infection in poultry-processing workers, Virginia, USA, 2008–2011. Emerg Infect Dis 19:286–288.
    333.
    Nielsen EM. 2002. Occurrence and strain diversity of thermophilic campylobacters in cattle of different age groups in dairy herds. Lett Appl Microbiol 35:85–89.
    334.
    Ellis-Iversen J, Cook AJ, Smith RP, Pritchard GC, Nielen M. 2009. Temporal patterns and risk factors for Escherichia coli O157 and Campylobacter spp. in young cattle. J Food Prot 72:490–496.
    335.
    Stanley KN, Wallace JS, Currie JE, Diggle PJ, Jones K. 1998. The seasonal variation of thermophilic campylobacters in beef cattle, dairy cattle and calves. J Appl Microbiol 85:472–480.
    336.
    Leatherbarrow AJ, Griffiths R, Hart CA, Kemp R, Williams NJ, Diggle PJ, Wright EJ, Sutherst J, Houghton P, French NP. 2007. Campylobacter lari: genotype and antibiotic resistance of isolates from cattle, wildlife and water in an area of mixed dairy farmland in the United Kingdom. Environ Microbiol 9:1772–1779.
    337.
    Guevremont E, Normand V, Lamoureux L, Cote C. 2008. Genetic detection of Campylobacter lanienae in fecal matter and stored manure from swine and dairy cattle. Foodborne Pathog Dis 5:361–364.
    338.
    Harvey RB, Young CR, Anderson RC, Droleskey RE, Genovese KJ, Egan LF, Nisbet DJ. 2000. Diminution of Campylobacter colonization in neonatal pigs reared off-sow. J Food Prot 63:1430–1432.
    339.
    Weijtens MJ, Bijker PG, Van der Plas J, Urlings HA, Biesheuvel MH. 1993. Prevalence of Campylobacter in pigs during fattening; an epidemiological study. Vet Q 15:138–143.
    340.
    Alter T, Gaull F, Kasimir S, Gurtler M, Mielke H, Linnebur M, Fehlhaber K. 2005. Prevalences and transmission routes of Campylobacter spp. strains within multiple pig farms. Vet Microbiol 108:251–261.
    341.
    Raji MA, Adekeye JO, Kwaga JK, Bale JO. 2000. Bioserogroups of Campylobacter species isolated from sheep in Kaduna State, Nigeria. Small Rumin Res 37:215–221.
    342.
    Zweifel C, Zychowska MA, Stephan R. 2004. Prevalence and characteristics of Shiga toxin-producing Escherichia coli, Salmonella spp. and Campylobacter spp. isolated from slaughtered sheep in Switzerland. Int J Food Microbiol 92:45–53.
    343.
    Cortes C, de la Fuente R, Contreras A, Sanchez A, Corrales JC, Martinez S, Orden JA. 2006. A survey of Salmonella spp and Campylobacter spp in dairy goat faeces and bulk tank milk in the Murcia region of Spain. Ir Vet J 59:391–393.
    344.
    Baker J, Barton MD, Lanser J. 1999. Campylobacter species in cats and dogs in South Australia. Aust Vet J 77:662–666.
    345.
    Chaban B, Ngeleka M, Hill JE. 2010. Detection and quantification of 14 Campylobacter species in pet dogs reveals an increase in species richness in feces of diarrheic animals. BMC Microbiol 10:73.
    346.
    Fox JG, Zanotti S, Jordan HV. 1981. The hamster as a reservoir of Campylobacter fetus subspecies jejuni. J Infect Dis 143:856.
    347.
    Fox JG, Hering AM, Ackerman JI, Taylor NS. 1983. The pet hamster as a potential reservoir of human campylobacteriosis. J Infect Dis 147:784.
    348.
    Fox JG, Ackerman JI, Newcomer CE. 1983. Ferret as a potential reservoir for human campylobacteriosis. Am J Vet Res 44:1049–1052.
    349.
    Giacomelli M, Piccirillo A. 2014. Pet reptiles as potential reservoir of Campylobacter species with zoonotic potential. Vet Rec 174:479.
    350.
    Kohler R, Krause G, Beutin L, Stephan R, Zweifel C. 2008. Shedding of food-borne pathogens and microbiological carcass contamination in rabbits at slaughter. Vet Microbiol 132:149–157.
    351.
    Luechtefeld NA, Blaser MJ, Reller LB, Wang WL. 1980. Isolation of Campylobacter fetus subsp. jejuni from migratory waterfowl. J Clin Microbiol 12:406–408.
    352.
    Kapperud G, Rosef O. 1983. Avian wildlife reservoir of Campylobacter fetus subsp. jejuni, Yersinia spp., and Salmonella spp. in Norway. Appl Environ Microbiol 45:375–380.
    353.
    Levre E, Valentini P, Brunetti M, Sacchelli F. 1989. Stationary and migratory avifauna as reservoirs of Salmonella, Yersinia and Campylobacter. Ann Ig 1:729–740.
    354.
    Llarena AK, Skarp-de Haan CP, Rossi M, Hanninen ML. 2015. Characterization of the Campylobacter jejuni population in the barnacle geese reservoir. Zoonoses Public Health 62:209–221.
    355.
    Lillehaug A, Monceyron Jonassen C, Bergsjo B, Hofshagen M, Tharaldsen J, Nesse LL, Handeland K. 2005. Screening of feral pigeon (Colomba livia), mallard (Anas platyrhynchos) and graylag goose (Anser anser) populations for Campylobacter spp., Salmonella spp., avian influenza virus and avian paramyxovirus. Acta Vet Scand 46:193–202.
    356.
    Antilles N, Sanglas A, Cerda-Cuellar M. 20 September 2013. Free-living waterfowl as a source of zoonotic bacteria in a dense wild bird population area in northeastern Spain. Transbound Emerg Dis doi:
    357.
    Marin C, Palomeque MD, Marco-Jimenez F, Vega S. 2014. Wild griffon vultures (Gyps fulvus) as a source of Salmonella and Campylobacter in eastern Spain. PLoS One 9:e94191.
    358.
    Sippy R, Sandoval-Green CM, Sahin O, Plummer P, Fairbanks WS, Zhang Q, Blanchong JA. 2012. Occurrence and molecular analysis of Campylobacter in wildlife on livestock farms. Vet Microbiol 157:369–375.
    359.
    Pacha RE, Clark GW, Williams EA, Carter AM, Scheffelmaier JJ, Debusschere P. 1987. Small rodents and other mammals associated with mountain meadows as reservoirs of Giardia spp. and Campylobacter spp. Appl Environ Microbiol 53:1574–1579.
    360.
    Wacheck S, Fredriksson-Ahomaa M, Konig M, Stolle A, Stephan R. 2010. Wild boars as an important reservoir for foodborne pathogens. Foodborne Pathog Dis 7:307–312.
    361.
    Bachand N, Ravel A, Onanga R, Arsenault J, Gonzalez JP. 2012. Public health significance of zoonotic bacterial pathogens from bushmeat sold in urban markets of Gabon, Central Africa. J Wildl Dis 48:785–789.
    362.
    Marin C, Ingresa-Capaccioni S, Gonzalez-Bodi S, Marco-Jimenez F, Vega S. 2013. Free-living turtles are a reservoir for Salmonella but not for Campylobacter. PLoS One 8:e72350.
    363.
    Petersen L, Nielsen EM, Engberg J, On SL, Dietz HH. 2001. Comparison of genotypes and serotypes of Campylobacter jejuni isolated from Danish wild mammals and birds and from broiler flocks and humans. Appl Environ Microbiol 67:3115–3121.
    364.
    Broman T, Palmgren H, Bergstrom S, Sellin M, Waldenstrom J, Danielsson-Tham ML, Olsen B. 2002. Campylobacter jejuni in black-headed gulls (Larus ridibundus): prevalence, genotypes, and influence on C. jejuni epidemiology. J Clin Microbiol 40:4594–4602.
    365.
    Hiett KL, Stern NJ, Fedorka-Cray P, Cox NA, Musgrove MT, Ladely S. 2002. Molecular subtype analyses of Campylobacter spp. from Arkansas and California poultry operations. Appl Environ Microbiol 68:6220–6236.
    366.
    Craven SE, Stern NJ, Line E, Bailey JS, Cox NA, Fedorka-Cray P. 2000. Determination of the incidence of Salmonella spp., Campylobacter jejuni, and Clostridium perfringens in wild birds near broiler chicken houses by sampling intestinal droppings. Avian Dis 44:715–720.
    367.
    Stern NJ, Myszewski MA, Barnhart HM, Dreesen DW. 1997. Flagellin A gene restriction fragment length polymorphism patterns of Campylobacter spp. isolates from broiler production sources. Avian Dis 41:899–905.
    368.
    Taylor DN, Brown M, McDermott KT. 1982. Waterborne transmission of Campylobacter enteritis. Microb Ecol 8:347–354.
    369.
    Rogol M, Sechter I, Falk H, Shtark Y, Alfi S, Greenberg Z, Mizrachi R. 1983. Waterborne outbreak of Campylobacter enteritis. Eur J Clin Microbiol 2:588–590.
    370.
    Hanninen ML, Haajanen H, Pummi T, Wermundsen K, Katila ML, Sarkkinen H, Miettinen I, Rautelin H. 2003. Detection and typing of Campylobacter jejuni and Campylobacter coli and analysis of indicator organisms in three waterborne outbreaks in Finland. Appl Environ Microbiol 69:1391–1396.
    371.
    Richardson G, Thomas DR, Smith RM, Nehaul L, Ribeiro CD, Brown AG, Salmon RL. 2007. A community outbreak of Campylobacter jejuni infection from a chlorinated public water supply. Epidemiol Infect 135:1151–1158.
    372.
    Kapperud G, Espeland G, Wahl E, Walde A, Herikstad H, Gustavsen S, Tveit I, Natas O, Bevanger L, Digranes A. 2003. Factors associated with increased and decreased risk of Campylobacter infection: a prospective case-control study in Norway. Am J Epidemiol 158:234–242.
    373.
    Arvanitidou M, Stathopoulos GA, Katsouyannopoulos VC. 1994. Isolation of Campylobacter and Yersinia spp. from drinking waters. J Travel Med 1:156–159.
    374.
    Popowski J, Lekowska-Kochaniak A, Korsak D. 1997. The incidence of heat tolerant Campylobacter in rivers and lakes of the Warsaw region. Rocz Panstw Zakl Hig 48:253–262.
    375.
    Galanis E, Mak S, Otterstatter M, Taylor M, Zubel M, Takaro TK, Kuo M, Michel P. 2014. The association between campylobacteriosis, agriculture and drinking water: a case-case study in a region of British Columbia, Canada, 2005–2009. Epidemiol Infect 142:2075–2084.
    376.
    Hanninen ML, Niskanen M, Korhonen L. 1998. Water as a reservoir for Campylobacter jejuni infection in cows studied by serotyping and pulsed-field gel electrophoresis (PFGE). Zentralbl Veterinarmed B 45:37–42.
    377.
    Carter PE, McTavish SM, Brooks HJ, Campbell D, Collins-Emerson JM, Midwinter AC, French NP. 2009. Novel clonal complexes with an unknown animal reservoir dominate Campylobacter jejuni isolates from river water in New Zealand. Appl Environ Microbiol 75:6038–6046.
    378.
    Champion OL, Gaunt MW, Gundogdu O, Elmi A, Witney AA, Hinds J, Dorrell N, Wren BW. 2005. Comparative phylogenomics of the food-borne pathogen Campylobacter jejuni reveals genetic markers predictive of infection source. Proc Natl Acad Sci U S A 102:16043–16048.
    379.
    Vally H, Glass K, Ford L, Hall G, Kirk MD, Shadbolt C, Veitch M, Fullerton KE, Musto J, Becker N. 2014. Proportion of illness acquired by foodborne transmission for nine enteric pathogens in Australia: an expert elicitation. Foodborne Pathog Dis 11:727–733.
    380.
    Centers for Disease Control and Prevention. 2013. Recurrent outbreak of Campylobacter jejuni infections associated with a raw milk dairy—Pennsylvania, April-May 2013. MMWR Morb Mortal Wkly Rep 62:702.
    381.
    Castrodale LJ, Gerlach RF, Xavier CM, Smith BJ, Cooper MP, McLaughlin JB. 2013. Sharing milk but not messages: campylobacteriosis associated with consumption of raw milk from a cow-share program in Alaska, 2011. J Food Prot 76:744–747.
    382.
    Longenberger AH, Palumbo AJ, Chu AK, Moll ME, Weltman A, Ostroff SM. 2013. Campylobacter jejuni infections associated with unpasteurized milk—multiple states, 2012. Clin Infect Dis 57:263–266.
    383.
    Mungai EA, Behravesh CB, Gould LH. 2015. Increased outbreaks associated with nonpasteurized milk, United States, 2007–2012. Emerg Infect Dis 21:119–122.
    384.
    Serraino A, Florio D, Giacometti F, Piva S, Mion D, Zanoni RG. 2013. Presence of Campylobacter and Arcobacter species in in-line milk filters of farms authorized to produce and sell raw milk and of a water buffalo dairy farm in Italy. J Dairy Sci 96:2801–2807.
    385.
    Koziel M, Lucey B, Bullman S, Corcoran GD, Sleator RD. 2012. Molecular-based detection of the gastrointestinal pathogen Campylobacter ureolyticus in unpasteurized milk samples from two cattle farms in Ireland. Gut Pathog 4:14.
    386.
    Revez J, Zhang J, Schott T, Kivisto R, Rossi M, Hanninen ML. 2014. Genomic variation between Campylobacter jejuni isolates associated with milk-borne-disease outbreaks. J Clin Microbiol 52:2782–2786.
    387.
    Jonsson ME, Chriel M, Norstrom M, Hofshagen M. 2012. Effect of climate and farm environment on Campylobacter spp. colonisation in Norwegian broiler flocks. Prev Vet Med 107:95–104.
    388.
    Strother KO, Steelman CD, Gbur EE. 2005. Reservoir competence of lesser mealworm (Coleoptera: Tenebrionidae) for Campylobacter jejuni (Campylobacterales: Campylobacteraceae). J Med Entomol 42:42–47.
    389.
    Skov MN, Spencer AG, Hald B, Petersen L, Nauerby B, Carstensen B, Madsen M. 2004. The role of litter beetles as potential reservoir for Salmonella enterica and thermophilic Campylobacter spp. between broiler flocks. Avian Dis 48:9–18.
    390.
    Axelsson-Olsson D, Waldenstrom J, Broman T, Olsen B, Holmberg M. 2005. Protozoan Acanthamoeba polyphaga as a potential reservoir for Campylobacter jejuni. Appl Environ Microbiol 71:987–992.
    391.
    Snelling WJ, McKenna JP, Hack CJ, Moore JE, Dooley JS. 2006. An examination of the diversity of a novel Campylobacter reservoir. Arch Microbiol 186:31–40.
    392.
    Barton MD. 2014. Impact of antibiotic use in the swine industry. Curr Opin Microbiol 19:9–15.
    393.
    Smith KE, Besser JM, Hedberg CW, Leano FT, Bender JB, Wicklund JH, Johnson BP, Moore KA, Osterholm MT. 1999. Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992–1998. Invest Team N Engl J Med 340:1525–1532.
    394.
    Gupta A, Nelson JM, Barrett TJ, Tauxe RV, Rossiter SP, Friedman CR, Joyce KW, Smith KE, Jones TF, Hawkins MA, Shiferaw B, Beebe JL, Vugia DJ, Rabatsky-Ehr T, Benson JA, Root TP, Angulo FJ. 2004. Antimicrobial resistance among Campylobacter strains, United States, 1997–2001. Emerg Infect Dis 10:1102–1109.
    395.
    Wieczorek K, Kania I, Osek J. 2013. Prevalence and antimicrobial resistance of Campylobacter spp. isolated from poultry carcasses in Poland. J Food Prot 76:1451–1455.
    396.
    Di Labio E, Regula G, Steiner A, Miserez R, Thomann A, Ledergerber U. 2007. Antimicrobial resistance in bacteria from Swiss veal calves at slaughter. Zoonoses Public Health 54:344–352.
    397.
    Chatre P, Haenni M, Meunier D, Botrel MA, Calavas D, Madec JY. 2010. Prevalence and antimicrobial resistance of Campylobacter jejuni and Campylobacter coli isolated from cattle between 2002 and 2006 in France. J Food Prot 73:825–831.
    398.
    Cheng AC, Turnidge J, Collignon P, Looke D, Barton M, Gottlieb T. 2012. Control of fluoroquinolone resistance through successful regulation, Australia. Emerg Infect Dis 18:1453–1460.
    399.
    Egger R, Korczak BM, Niederer L, Overesch G, Kuhnert P. 2012. Genotypes and antibiotic resistance of Campylobacter coli in fattening pigs. Vet Microbiol 155:272–278.
    400.
    Juntunen P, Olkkola S, Hanninen ML. 2011. Longitudinal on-farm study of the development of antimicrobial resistance in Campylobacter coli from pigs before and after danofloxacin and tylosin treatments. Vet Microbiol 150:322–330.
    401.
    EFSA. 2011. Scientific opinion on Campylobacter in broiler meat production: control options and performance objectives and/or targets at different stages of the food chain. EFSA J 9:2105.
    402.
    Newell DG, Elvers KT, Dopfer D, Hansson I, Jones P, James S, Gittins J, Stern NJ, Davies R, Connerton I, Pearson D, Salvat G, Allen VM. 2011. Biosecurity-based interventions and strategies to reduce Campylobacter spp. on poultry farms. Appl Environ Microbiol 77:8605–8614.
    403.
    van Gerwe T, Bouma A, Wagenaar JA, Jacobs-Reitsma WF, Stegeman A. 2010. Comparison of Campylobacter levels in crops and ceca of broilers at slaughter. Avian Dis 54:1072–1074.
    404.
    Humphrey S, Chaloner G, Kemmett K, Davidson N, Williams N, Kipar A, Humphrey T, Wigley P. 2014. Campylobacter jejuni is not merely a commensal in commercial broiler chickens and affects bird welfare. mBio 5:e01364-14.
    405.
    Bahrndorff S, Rangstrup-Christensen L, Nordentoft S, Hald B. 2013. Foodborne disease prevention and broiler chickens with reduced Campylobacter infection. Emerg Infect Dis 19:425–430.
    406.
    Yano S, Kira T, Morishita Y, Ishihara K, Asai T, Iwata T, Akiba M, Murase T. 2013. Colonization of chicken flocks by Campylobacter jejuni in multiple farms in Japan. Poult Sci 92:375–381.
    407.
    Lammerding AM, Fazil A. 2000. Hazard identification and exposure assessment for microbial food safety risk assessment. Int J Food Microbiol 58:147–157.
    408.
    Svetoch EA, Stern NJ. 2010. Bacteriocins to control Campylobacter spp. in poultry—a review. Poult Sci 89:1763–1768.
    409.
    Hoang KV, Stern NJ, Lin J. 2011. Development and stability of bacteriocin resistance in Campylobacter spp. J Appl Microbiol 111:1544–1550.
    410.
    Wagenaar JA, Van Bergen MA, Mueller MA, Wassenaar TM, Carlton RM. 2005. Phage therapy reduces Campylobacter jejuni colonization in broilers. Vet Microbiol 109:275–283.
    411.
    Atterbury RJ, Dillon E, Swift C, Connerton PL, Frost JA, Dodd CE, Rees CE, Connerton IF. 2005. Correlation of Campylobacter bacteriophage with reduced presence of hosts in broiler chicken ceca. Appl Environ Microbiol 71:4885–4887.
    412.
    Loc Carrillo C, Atterbury RJ, el-Shibiny A, Connerton PL, Dillon E, Scott A, Connerton IF. 2005. Bacteriophage therapy to reduce Campylobacter jejuni colonization of broiler chickens. Appl Environ Microbiol 71:6554–6563.
    413.
    El-Shibiny A, Scott A, Timms A, Metawea Y, Connerton P, Connerton I. 2009. Application of a group II Campylobacter bacteriophage to reduce strains of Campylobacter jejuni and Campylobacter coli colonizing broiler chickens. J Food Prot 72:733–740.
    414.
    Carvalho CM, Gannon BW, Halfhide DE, Santos SB, Hayes CM, Roe JM, Azeredo J. 2010. The in vivo efficacy of two administration routes of a phage cocktail to reduce numbers of Campylobacter coli and Campylobacter jejuni in chickens. BMC Microbiol 10:232.
    415.
    Kittler S, Fischer S, Abdulmawjood A, Glunder G, Klein G. 2013. Effect of bacteriophage application on Campylobacter jejuni loads in commercial broiler flocks. Appl Environ Microbiol 79:7525–7533.
    416.
    Hermans D, Van Deun K, Messens W, Martel A, Van Immerseel F, Haesebrouck F, Rasschaert G, Heyndrickx M, Pasmans F. 2011. Campylobacter control in poultry by current intervention measures ineffective: urgent need for intensified fundamental research. Vet Microbiol 152:219–228.
    417.
    Fischer S, Kittler S, Klein G, Glunder G. 2013. Impact of a single phage and a phage cocktail application in broilers on reduction of Campylobacter jejuni and development of resistance. PLoS One 8:e78543.
    418.
    Ghareeb K, Awad WA, Mohnl M, Porta R, Biarnes M, Bohm J, Schatzmayr G. 2012. Evaluating the efficacy of an avian-specific probiotic to reduce the colonization of Campylobacter jejuni in broiler chickens. Poult Sci 91:1825–1832.
    419.
    Nishiyama K, Seto Y, Yoshioka K, Kakuda T, Takai S, Yamamoto Y, Mukai T. 2014. Lactobacillus gasseri SBT2055 reduces infection by and colonization of Campylobacter jejuni. PLoS One 9:e108827.
    420.
    Santini C, Baffoni L, Gaggia F, Granata M, Gasbarri R, Di Gioia D, Biavati B. 2010. Characterization of probiotic strains: an application as feed additives in poultry against Campylobacter jejuni. Int J Food Microbiol 141(Suppl 1):S98–S108.
    421.
    Saxena M, John B, Mu M, Van TTH, Taki A, Coloe PJ, Smooker PM. 2013. Strategies to reduce Campylobacter colonisation in chickens. Procedia Vaccinol 7:40–43.
    422.
    Annamalai T, Pina-Mimbela R, Kumar A, Binjawadagi B, Liu Z, Renukaradhya GJ, Rajashekara G. 2013. Evaluation of nanoparticle-encapsulated outer membrane proteins for the control of Campylobacter jejuni colonization in chickens. Poult Sci 92:2201–2211.
    423.
    Lake RJ, Horn BJ, Dunn AH, Parris R, Green FT, McNickle DC. 2013. Cost-effectiveness of interventions to control Campylobacter in the New Zealand poultry meat food supply. J Food Prot 76:1161–1167.
    424.
    Steens A, Eriksen HM, Blystad H. 2014. What are the most important infectious diseases among those ≥65 years: a comprehensive analysis on notifiable diseases, Norway, 1993–2011. BMC Infect Dis 14:57.
    425.
    Sadkowska-Todys M, Kucharczyk B. 2013. Campylobacteriosis in Poland in 2011. Przegl Epidemiol 67:227–229, 341–342.
    426.
    O'Reilly CE, Jaron P, Ochieng B, Nyaguara A, Tate JE, Parsons MB, Bopp CA, Williams KA, Vinje J, Blanton E, Wannemuehler KA, Vulule J, Laserson KF, Breiman RF, Feikin DR, Widdowson MA, Mintz E. 2012. Risk factors for death among children less than 5 years old hospitalized with diarrhea in rural western Kenya, 2005–2007: a cohort study. PLoS Med 9:e1001256.
    427.
    Lee G, Pan W, Penataro Yori P, Paredes Olortegui M, Tilley D, Gregory M, Oberhelman R, Burga R, Chavez CB, Kosek M. 2013. Symptomatic and asymptomatic Campylobacter infections associated with reduced growth in Peruvian children. PLoS Negl Trop Dis 7:e2036.
    428.
    Zaidi MB, Campos FD, Estrada-Garcia T, Gutierrez F, Leon M, Chim R, Calva JJ. 2012. Burden and transmission of zoonotic foodborne disease in a rural community in Mexico. Clin Infect Dis 55:51–60.
    429.
    Yu JH, Kim NY, Cho NG, Kim JH, Kang YA, Lee HG. 2010. Epidemiology of Campylobacter jejuni outbreak in a middle school in Incheon, Korea. J Korean Med Sci 25:1595–1600.
    430.
    Parry A, Fearnley E, Denehy E. 2012. ‘Surprise’: outbreak of Campylobacter infection associated with chicken liver pate at a surprise birthday party, Adelaide, Australia, 2012. Western Pac Surveill Response J 3:16–19.
    431.
    Merritt T, Combs B, Pingault N. 2011. Campylobacter outbreaks associated with poultry liver dishes. Commun Dis Intell Q Rep 35:299–300.
    432.
    Wensley A, Coole L. 2013. Cohort study of a dual-pathogen point source outbreak associated with the consumption of chicken liver pate, UK, October 2009. J Public Health (Oxf) 35:585–589.
    433.
    Inns T, Foster K, Gorton R. 2010. Cohort study of a campylobacteriosis outbreak associated with chicken liver parfait, United Kingdom, June 2010. Euro Surveill 15:19704. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19704.
    434.
    Griffiths SL, Salmon RL, Mason BW, Elliott C, Thomas DR, Davies C. 2010. Using the Internet for rapid investigation of an outbreak of diarrhoeal illness in mountain bikers. Epidemiol Infect 138:1704–1711.
    435.
    Farmer S, Keenan A, Vivancos R. 2012. Food-borne Campylobacter outbreak in Liverpool associated with cross-contamination from chicken liver parfait: implications for investigation of similar outbreaks. Public Health 126:657–659.
    436.
    Abid M, Wimalarathna H, Mills J, Saldana L, Pang W, Richardson JF, Maiden MCJ, McCarthy ND. 2013. Duck liver-associated outbreak of campylobacteriosis among humans, United Kingdom, 2011. Emerg Infect Dis 9:1310–1313.
    437.
    Rasanen S, Lappalainen S, Kaikkonen S, Hamalainen M, Salminen M, Vesikari T. 2010. Mixed viral infections causing acute gastroenteritis in children in a waterborne outbreak. Epidemiol Infect 138:1227–1234.
    438.
    Breitenmoser A, Fretz R, Schmid J, Besl A, Etter R. 2011. Outbreak of acute gastroenteritis due to a washwater-contaminated water supply, Switzerland, 2008. J Water Health 9:569–576.
    439.
    Gubbels SM, Kuhn KG, Larsson JT, Adelhardt M, Engberg J, Ingildsen P, Hollesen LW, Muchitsch S, Molbak K, Ethelberg S. 2012. A waterborne outbreak with a single clone of Campylobacter jejuni in the Danish town of Koge in May 2010. Scand J Infect Dis 44:586–594.
    440.
    Moller-Stray J, Eriksen HM, Bruheim T, Kapperud G, Lindstedt BA, Skeie A, Sunde M, Urdahl AM, Oygard B, Vold L. 2012. Two outbreaks of diarrhoea in nurseries in Norway after farm visits, April to May 2009. Euro Surveill 17:20321. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20321.
    441.
    Karagiannis I, Sideroglou T, Gkolfinopoulou K, Tsouri A, Lampousaki D, Velonakis EN, Scoulica EV, Mellou K, Panagiotopoulos T, Bonovas S. 2010. A waterborne Campylobacter jejuni outbreak on a Greek island. Epidemiol Infect 138:1726–1734.
    442.
    Gardner TJ, Fitzgerald C, Xavier C, Klein R, Pruckler J, Stroika S, McLaughlin JB. 2011. Outbreak of campylobacteriosis associated with consumption of raw peas. Clin Infect Dis 53:26–32.
    443.
    Stuart TL, Sandhu J, Stirling R, Corder J, Ellis A, Misa P, Goh S, Wong B, Martiquet P, Hoang L, Galanis E. 2010. Campylobacteriosis outbreak associated with ingestion of mud during a mountain bike race. Epidemiol Infect 138:1695–1703.
    444.
    Gaudreau C, Helferty M, Sylvestre JL, Allard R, Pilon PA, Poisson M, Bekal S. 2013. Campylobacter coli outbreak in men who have sex with men, Quebec, Canada, 2010–2011. Emerg Infect Dis 19:764–767.
    445.
    Zeigler M, Claar C, Rice D, Davis J, Frazier T, Turner A, Kelley C, Capps J, Kent A, Hubbard V, Ritenour C, Tuscano C, Qiu-Shultz Z, Leaumont CF. 2014. Outbreak of campylobacteriosis associated with a long-distance obstacle adventure race—Nevada, October 2012. MMWR Morb Mortal Wkly Rep 63:375–378.
    446.
    Bartholomew N, Brunton C, Mitchell P, Williamson J, Gilpin B. 2014. A waterborne outbreak of campylobacteriosis in the South Island of New Zealand due to a failure to implement a multi-barrier approach. J Water Health 12:555–563.
    447.
    Edwards DS, Milne LM, Morrow K, Sheridan P, Verlander NQ, Mulla R, Richardson JF, Pender A, Lilley M, Reacher M. 2014. Campylobacteriosis outbreak associated with consumption of undercooked chicken liver pate in the East of England, September 2011: identification of a dose-response risk. Epidemiol Infect 142:352–357.

    Author Bios

    Nadeem O. Kaakoush
    School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
    Nadeem O. Kaakoush, Ph.D., undertook his doctoral studies in pathology at the School of Medical Sciences at the University of New South Wales (UNSW), Sydney, Australia, where he investigated pathogenic Helicobacter and Campylobacter species. Following his doctoral studies, he took up a Research Associate position at the School of Biotechnology and Biomolecular Sciences at UNSW, examining the role of mucosa-associated bacteria in inflammatory bowel diseases. In 2011, Dr. Kaakoush was awarded a National Health and Medical Research Council early career fellowship to further his research in this field, and he has since expanded his research to investigate the overall clinical relevance of emerging Campylobacter species.
    Natalia Castaño-Rodríguez
    School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
    Natalia Castaño-Rodríguez holds an M.D. from Del Rosario University, Colombia, and an M.Phil. and Ph.D. from the University of New South Wales, Sydney, Australia. She is currently a Research Associate working in the Helicobacter and Campylobacter laboratory at the University of New South Wales. She has extensive experience conducting research in the fields of microbiology, immunology, and host immunogenetics, with a particular emphasis on the role of pattern recognition receptors in the host inflammatory response following Helicobacter and Campylobacter infections. More recently, her efforts have been focused on investigation of the role of host immunogenetics in Helicobacter pylori-related gastric cancer.
    Hazel M. Mitchell
    School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
    Hazel M. Mitchell was awarded a B.Sc. (with honors) from the University of Strathclyde, Glasgow, United Kingdom, a Dip.Ed. from the Jordanhill College of Education, Glasgow, and a Ph.D. from the University of New South Wales, Sydney, Australia. She previously held the positions of Senior Lecturer and Associate Professor in the School of Biotechnology and Biomolecular Sciences at the University of New South Wales and was promoted to Professor of Medical Microbiology in 2007. Her research studies focus on the role of mucosa-associated bacteria in gastrointestinal disease, in particular the role of emerging Campylobacter species and the intestinal microbiota in inflammatory bowel disease and the role of Helicobacter pylori and host genetic polymorphisms in gastric cancer. She is on the editorial board of Helicobacter and is an Associate Editor of Gut Pathogens. She has published 132 peer-reviewed journal articles and 16 book chapters and coedited a book entitled Helicobacter pylori in the 21st Century.
    School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
    Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
    Si Ming Man received his B.Med.Sc. (with honors) and M.S. (research) from the University of New South Wales, Sydney, Australia, for his work on Campylobacter infection in inflammatory bowel disease. He then obtained his Ph.D. from the University of Cambridge, United Kingdom, where he investigated the role of inflammasome activation in the host defense against Salmonella infection. He is a recipient of the National Health and Medical Research Council R. G. Menzies Fellowship and is currently based at St. Jude Children's Research Hospital, Memphis, TN. He has long-standing interests in understanding the molecular mechanisms regulating innate immunity in response to gastrointestinal pathogens. His current research program focuses on elucidating the molecular mechanisms involved in innate immune recognition of bacterial pathogens.

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    Clinical Microbiology Reviews
    Volume 28Number 3July 2015
    Pages: 687 - 720

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    Published online: 10 June 2015

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    Authors

    Nadeem O. Kaakoush
    School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
    Natalia Castaño-Rodríguez
    School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
    Hazel M. Mitchell
    School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
    School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
    Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Notes

    N.O.K. and N.C.-R. contributed equally to this article.

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  • Clinical Microbiology ReviewsArticle
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    SUMMARY

    In recent decades, several new diseases have emerged in different geographical areas, with pathogens including Ebola virus, Zika virus, Nipah virus, and coronaviruses (CoVs). Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses, such as Ebola virus, avian H7N9, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus has been transferred from an animal source, such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus.

    REFERENCES

    1.
    Rodriguez-Morales AJ, Bonilla-Aldana DK, Balbin-Ramon GJ, Rabaan AA, Sah R, Paniz-Mondolfi A, Pagliano P, Esposito S. 2020. History is repeating itself: probable zoonotic spillover as the cause of the 2019 novel coronavirus epidemic. Infez Med 28:3–5.
    2.
    Gralinski LE, Menachery VD. 2020. Return of the coronavirus: 2019-nCoV. Viruses 12:135.
    3.
    Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W, China Novel Coronavirus Investigating and Research Team. 2020. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 382:727–733.
    4.
    Wei X, Li X, Cui J. 2020. Evolutionary perspectives on novel coronaviruses identified in pneumonia cases in China. Natl Sci Rev 7:239–242.
    5.
    Munster VJ, Koopmans M, van Doremalen N, van Riel D, de Wit E. 2020. A novel coronavirus emerging in China-key questions for impact assessment. N Engl J Med 382:692–694.
    6.
    Fan Y, Zhao K, Shi ZL, Zhou P. 2019. Bat coronaviruses in China. Viruses 11:210.
    7.
    Lu H. 2020. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends 14:69–71.
    8.
    Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, Montgomery SA, Hogg A, Babusis D, Clarke MO, Spahn JE, Bauer L, Sellers S, Porter D, Feng JY, Cihlar T, Jordan R, Denison MR, Baric RS. 2020. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun 11:222.
    9.
    Pillaiyar T, Meenakshisundaram S, Manickam M. 2020. Recent discovery and development of inhibitors targeting coronaviruses. Drug Discov Today 25:668–688.
    10.
    Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, Liu W, Bi Y, Gao GF. 2016. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol 24:490–502.
    11.
    Ng OW, Tan YJ. 2017. Understanding bat SARS-like coronaviruses for the preparation of future corona virus outbreaks–implications for coronavirus vaccine development. Hum Vaccin Immunother 13:186–189.
    12.
    Bonilla-Aldana DK, Holguin-Rivera Y, Cortes-Bonilla I, Cardona-Trujillo MC, García-Barco A, Bedoya-Arias HA, Rabaan AA, Sah R, Rodriguez-Morales AJ. 6 February 2020. Coronavirus infections reported by ProMED, February 2000–January 2020. Travel Med Infect Dis doi:
    13.
    Zhang L, Shen FM, Chen F, Lin Z. 3 February 2020. Origin and evolution of the 2019 novel coronavirus. Clin Infect Dis doi:
    14.
    Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, Li SB, Wang HY, Zhang S, Gao HN, Sheng JF, Cai HL, Qiu YQ, Li LJ. 2020. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ 368:m606.
    15.
    Chen J. 2020. Pathogenicity and transmissibility of 2019-nCoV-A quick overview and comparison with other emerging viruses. Microbes Infect 22:69–71.
    16.
    Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P, Meng J, Zhu Z, Zhang Z, Wang J, Sheng J, Quan L, Xia Z, Tan W, Cheng G, Jiang T. 2020. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe 27:325–328.
    17.
    Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. 2020. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395:565–574.
    18.
    Kui L, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, Xiao W, Wang YN, Zhong MH, Li CH, Li GC, Liu HG. 2020. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J 133:1025–1031.
    19.
    Cyranoski D. 2020. This scientist hopes to test coronavirus drugs on animals in locked-down Wuhan. Nature 577:607.
    20.
    Dhama K, Pawaiya RVS, Chakrabort S, Tiwari R, Saminathan M, Verma AK. 2014. Coronavirus infection in equines: a review. Asian J Anim Vet Adv 9:164–176.
    21.
    Zaher NH, Mostafa MI, Altaher AY. 2020. Design, synthesis and molecular docking of novel triazole derivatives as potential CoV helicase inhibitors. Acta Pharm 70:145–159.
    22.
    Bonilla-Aldana DK, Villamil-Gómez WE, Rabaan AA, Rodriguez-Morales AJ. 2020. Una nueva zoonosis viral de preocupación global: COVID-19, enfermedad por coronavirus 2019. Iatreia 33:107–110.
    23.
    Weiss SR, Leibowitz JL. 2011. Coronavirus pathogenesis. Adv Virus Res 81:85–164.
    24.
    Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, Pan P, Wang W, Hu D, Liu X, Zhang Q, Wu J. 2020. Coronavirus infections and immune responses. J Med Virol 92:424–432.
    25.
    WHO. 2020. Coronavirus disease 2019 (COVID-19) situation report–114 (13th May, 2020). https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200513-covid-19-sitrep-114.pdf?sfvrsn=17ebbbe_4. Accessed on 13 May 2020.
    26.
    Gorbalenya AE, Baker SC, Baric RS, de Groot RJ, Drosten C, Gulyaeva AA, Haagmans BL, Lauber C, Leontovich AM, Neuman BW, Penzar D. 2020. Severe acute respiratory syndrome-related coronavirus: the species and its viruses–a statement of the Coronavirus Study Group. bioRxiv https://doi.org/10.1101/2020.02.07.937862.
    27.
    Chen Y, Liu Q, Guo D. 2020. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol 92:418–423.
    28.
    Lai MMC, Holmes KV. 2001. Coronaviridae: the viruses and their replication, p 1163–1185. In Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE (ed), Fields virology, 4th ed. Lippincott-Raven, Philadephia, PA.
    29.
    Woo PC, Lau SK, Lam CS, Lau CC, Tsang AK, Lau JH, Bai R, Teng JL, Tsang CC, Wang M, Zheng BJ, Chan KH, Yuen KY. 2012. Discovery of seven novel mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus. J Virol 86:3995–4008.
    30.
    Fehr AR, Perlman S. 2015. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol 1282:1–23.
    31.
    Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY. 2020. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect 9:221–236.
    32.
    Brian DA, Baric RS. 2005. Coronavirus genome structure and replication. Curr Topics Microbiol Immunol 287:1–30.
    33.
    Nakagawa K, Lokugamage KG, Makino S. 2016. Viral and cellular mRNA translation in coronavirus-infected cells. Adv Virus Res 96:165–192.
    34.
    Snijder EJ, van der Meer Y, Zevenhoven-Dobbe J, Onderwater JJM, van der Meulen J, Koerten HK, Mommaas AM. 2006. Ultrastructure and origin of membrane vesicles associated with the severe acute respiratory syndrome coronavirus replication complex. J Virol 80:5927–5940.
    35.
    Hussain S, Pan J, Chen Y, Yang Y, Xu J, Peng Y, Wu Y, Li Z, Zhu Y, Tien P, Guo D. 2005. Identification of novel subgenomic RNAs and noncanonical transcription initiation signals of severe acute respiratory syndrome coronavirus. J Virol 79:5288–5295.
    36.
    Malik YS, Sircar S, Bhat S, Sharun K, Dhama K, Dadar M, Tiwari R, Chaicumpa W. 2020. Emerging novel coronavirus (2019-nCoV)—current scenario, evolutionary perspective based on genome analysis and recent developments. Vet Q 40:68–76.
    37.
    Ren LL, Wang YM, Wu ZQ, Xiang ZC, Guo L, Xu T, Jiang YZ, Xiong Y, Li YJ, Li H, Fan GH, Gu XY, Xiao Y, Gao H, Xu JY, Yang F, Wang XM, Wu C, Chen L, Liu YW, Liu B, Yang J, Wang XR, Dong J, Li L, Huang CL, Zhao JP, Hu Y, Cheng ZS, Liu LL, Qian ZH, Qin C, Jin Q, Cao B, Wang JW. 2020. Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin Med J 133:1015–1024.
    38.
    Hu B, Ge X, Wang LF, Shi Z. 2015. Bat origin of human coronaviruses. Virol J 12:221.
    39.
    Li B, Si HR, Zhu Y, Yang XL, Anderson DE, Shi ZL, Wang LF, Zhou P. 2020. Discovery of bat coronaviruses through surveillance and probe capture-based next-generation sequencing. mSphere 5:e00807-19.
    40.
    Wang LF, Eaton BT. 2007. Bats, civets and the emergence of SARS, p 325–344. In Wildlife and emerging zoonotic diseases: the biology, circumstances and consequences of cross-species transmission. Springer, Berlin, Germany.
    41.
    Hemida MG. 2019. Middle East respiratory syndrome coronavirus and the One Health concept. Peer J 7:e7556.
    42.
    Masters PS. 2006. The molecular biology of coronaviruses. Adv Virus Res 66:193–292.
    43.
    Belouzard S, Millet JK, Licitra BN, Whittaker GR. 2012. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses 4:1011–1033.
    44.
    Beniac DR, Andonov A, Grudeski E, Booth TF. 2006. Architecture of the SARS coronavirus prefusion spike. Nat Struct Mol Biol 13:751–752.
    45.
    Li F. 2016. Structure, function, and evolution of coronavirus spike proteins. Annu Rev Virol 3:237–261.
    46.
    Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH, Mazet JK, Hu B, Zhang W, Peng C, Zhang YJ, Luo CM, Tan B, Wang N, Zhu Y, Crameri G, Zhang SY, Wang LF, Daszak P, Shi ZL. 2013. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 503:535–538.
    47.
    Li X, Song Y, Wong G, Cui J. 2020. Bat origin of a new human coronavirus: there and back again. Sci China Life Sci 63:461–462.
    48.
    Neuman BW, Kiss G, Kunding AH, Bhella D, Baksh MF, Connelly S, Droese B, Klaus JP, Makino S, Sawicki SG, Siddell SG, Stamou DG, Wilson IA, Kuhn P, Buchmeier MJ. 2011. A structural analysis of M protein in coronavirus assembly and morphology. J Struct Biol 174:11–22.
    49.
    Nal B, Chan C, Kien F, Siu L, Tse J, Chu K, Kam J, Staropoli I, Crescenzo-Chaigne B, Escriou N, van der Werf S, Yuen K-Y, Altmeyer R. 2005. Differential maturation and subcellular localization of severe acute respiratory syndrome coronavirus surface proteins S, M and E. J Gen Virol 86:1423–1434.
    50.
    Arndt AL, Larson BJ, Hogue BG. 2010. A conserved domain in the coronavirus membrane protein tail is important for virus assembly. J Virol 84:11418–11428.
    51.
    Schoeman D, Fielding BC. 2019. Coronavirus envelope protein: current knowledge. Virol J 16:69.
    52.
    Nieto-Torres JL, DeDiego ML, Verdiá-Báguena C, Jimenez-Guardeño JM, Regla-Nava JA, Fernandez-Delgado R, Castaño-Rodriguez C, Alcaraz A, Torres J, Aguilella VM, Enjuanes L. 2014. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis. PLoS Pathog 10:e1004077.
    53.
    Pervushin K, Tan E, Parthasarathy K, Lin X, Jiang FL, Yu D, Vararattanavech A, Soong TW, Liu DX, Torres J. 2009. Structure and inhibition of the SARS coronavirus envelope protein ion channel. PLoS Pathog 5:e1000511.
    54.
    DeDiego ML, Alvarez E, Almazán F, Rejas MT, Lamirande E, Roberts A, Shieh WJ, Zaki SR, Subbarao K, Enjuanes L. 2007. A severe acute respiratory syndrome corona virus that lacks the E gene is attenuated in vitro and in vivo. J Virol 81:1701–1713.
    55.
    Chang C-K, Sue S-C, Yu T-H, Hsieh C-M, Tsai C-K, Chiang Y-C, Lee S-J, Hsiao H-H, Wu W-J, Chang W-L, Lin C-H, Huang T-H. 2006. Modular organization of SARS coronavirus nucleocapsid protein. J Biomed Sci 13:59–72.
    56.
    Sheikh A, Al-Taher A, Al-Nazawi M, Al-Mubarak AI, Kandeel M. 2020. Analysis of preferred codon usage in the coronavirus N genes and their implications for genome evolution and vaccine design. J Virol Methods 277:113806.
    57.
    McBride R, van Zyl M, Fielding BC. 2014. The coronavirus nucleocapsid is a multifunctional protein. Viruses 6:2991–3018.
    58.
    Fan H, Ooi A, Tan YW, Wang S, Fang S, Liu DX, Lescar J. 2005. The nucleocapsid protein of coronavirus infectious bronchitis virus: crystal structure of its N-terminal domain and multimerization properties. Structure 13:1859–1868.
    59.
    Hurst KR, Koetzner CA, Masters PS. 2009. Identification of in vivo-interacting domains of the murine coronavirus nucleocapsid protein. J Virol 83:7221–7234.
    60.
    Stohlman SA, Baric RS, Nelson GN, Soe LH, Welter LM, Deans RJ. 1988. Specific interaction between coronavirus leader RNA and nucleocapsid protein. J Virol 62:4288–4295.
    61.
    You J, Dove BK, Enjuanes L, DeDiego ML, Alvarez E, Howell G, Heinen P, Zambon M, Hiscox JA. 2005. Subcellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein. J Gen Virol 86:3303–3310.
    62.
    Cui L, Wang H, Ji Y, Yang J, Xu S, Huang X, Wang Z, Qin L, Tien P, Zhou X, Guo D, Chen Y. 2015. The nucleocapsid protein of coronaviruses acts as a viral suppressor of RNA silencing in mammalian cells. J Virol 89:9029–9043.
    63.
    Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Shi ZL. 2020. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. bioRxiv https://doi.org/10.1101/2020.01.22.914952.
    64.
    Bastola A, Sah R, Rodriguez-Morales AJ, Lal BK, Jha R, Ojha HC, Shrestha B, Chu DKW, Poon LLM, Costello A, Morita K, Pandey BD. 2020. The first 2019 novel coronavirus case in Nepal. Lancet Infect Dis 20:279–280.
    65.
    Velavan TP, Meyer CG. 2020. The Covid-19 epidemic. Trop Med Int Health 25:278–280.
    66.
    Ayittey FK, Ayittey MK, Chiwero NB, Kamasah JS, Dzuvor C. 2020. Economic impacts of Wuhan 2019-nCoV on China and the world. J Med Virol 92:473–475.
    67.
    Qiu H, Tong Z, Ma P, Hu M, Peng Z, Wu W, Du B, China Critical Care Clinical Trials Group (CCCCTG). 2020. Intensive care during the coronavirus epidemic. Intensive Care Med 46:576–578.
    68.
    Cheng VCC, Wong SC, To KKW, Ho PL, Yuen KY. 2020. Preparedness and proactive infection control measures against the emerging Wuhan coronavirus pneumonia in China. J Hosp Infect 104:254–255.
    69.
    Liu SL, Saif L. 2020. Emerging viruses without borders: the Wuhan coronavirus. Viruses 12:130.
    70.
    Mahase E. 2020. China coronavirus: what do we know so far? BMJ 368:m308.
    71.
    Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, Ippolito G, Mchugh TD, Memish ZA, Drosten C, Zumla A, Petersen E. 2020. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health—the latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis 91:264–266.
    72.
    Lu H, Stratton CW, Tang YW. 2020. Outbreak of pneumonia of unknown etiology in Wuhan China: the mystery and the miracle. J Med Virol 92:401–402.
    73.
    Nishiura H, Kobayashi T, Yang Y, Hayashi K, Miyama T, Kinoshita R, Linton NM, Jung SM, Yuan B, Suzuki A, Akhmetzhanov AR. 2020. The rate of underascertainment of novel corona virus (2019-nCoV) infection: estimation using Japanese passengers data on evacuation flights. J Clin Med 9:419.
    74.
    Nishiura H, Linton NM, Akhmetzhanov AR. 2020. Initial cluster of novel coronavirus (2019-nCoV) infections in Wuhan, China, is consistent with substantial human-to-human transmission. J Clin Med 9:488.
    75.
    Parry J. 2020. China coronavirus: cases surge as official admits human to human transmission. BMJ 368:m236.
    76.
    Zhao S, Lin Q, Ran J, Musa SS, Yang G, Wang W, Lou Y, Gao D, Yang L, He D, Wang MH. 2020. Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: a data-driven analysis in the early phase of the outbreak. Int J Infect Dis 92:214–217.
    77.
    Liu Y, Gayle AA, Wilder-Smith A, Rocklöv J. 13 February 2020. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med 27:taaa021.
    78.
    Guan Y, Zheng BJ, He YQ, Liu XL, Zhuang ZX, Cheung CL, Luo SW, Li PH, Zhang LJ, Guan YJ, Butt KM, Wong KL, Chan KW, Lim W, Shortridge KF, Yuen KY, Peiris JS, Poon LL. 2003. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 302:276–278.
    79.
    Monchatre-Leroy E, Boue F, Boucher JM, Renault C, Moutou F, Ar Gouilh M, Umhang G. 2017. Identification of alpha and beta coronavirus in wildlife species in France: bats, rodents, rabbits, and hedgehogs. Viruses 9:364.
    80.
    Shen K, Yang Y, Wang T, Zhao D, Jiang Y, Jin R, Zheng Y, Xu B, Xie Z, Lin L, Shang Y, Lu X, Shu S, Bai Y, Deng J, Lu M, Ye L, Wang X, Wang Y, Gao L. 2020. Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts’ consensus statement. World J Pediatr 7:1–9.
    81.
    Lin L, Li TS. 2020. Interpretation of guidelines for the diagnosis and treatment of novel coronavirus (2019-nCoV) infection by the National Health Commission (trial version 5). Zhonghua Yi Xue Za Zhi 100:E001.
    82.
    Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, Yu J, Kang M, Song Y, Xia J, Guo Q, Song T, He J, Yen HL, Peiris M, Wu J. 2020. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med 382:1177–1179.
    83.
    Hao W, Li M, Huang X. 19 February 2020. First atypical case of 2019 novel coronavirus in Yan’an, China. Clin Microbiol Infect doi:
    84.
    Zhou T, Liu Q, Yang Z, Liao J, Yang K, Bai W, Lu X, Zhang W. 2020. Preliminary prediction of the basic reproduction number of the Wuhan novel coronavirus 2019-nCoV. J Evid Based Med 13:3–7.
    85.
    Wang L, Su S, Bi Y, Wong G, Gao GF. 2018. Bat-origin coronaviruses expand their host range to pigs. Trends Microbiol 26:466–470.
    86.
    Benvenuto D, Giovanetti M, Salemi M, Prosperi M, De Flora C, Jr, Alcantara LC, Angeletti S, Ciccozzi M. 2020. The global spread of 2019-nCoV: a molecular evolutionary analysis. Pathog Glob Health 114:64–67.
    87.
    Wan Y, Shang J, Graham R, Baric RS, Li F. 2020. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS. J Virol 94:e00127-20.
    88.
    Biscayart C, Angeleri P, Lloveras S, Chaves T, Schlagenhauf P, Rodríguez-Morales AJ. 2020. The next big threat to global health? 2019 novel coronavirus (2019-nCoV): what advice can we give to travellers? Interim recommendations January 2020, from the Latin-American Society for Travel Medicine (SLAMVI). Travel Med Infect Dis 33:101567.
    89.
    Rodriguez-Morales AJ, MacGregor K, Kanagarajah S, Patel D, Schlagenhauf P. 2020. Going global—travel and the 2019 novel coronavirus. Travel Med Infect Dis 33:101578.
    90.
    Peiris JS, Guan Y, Yuen KY. 2004. Severe acute respiratory syndrome. Nat Med 10:S88–S97.
    91.
    Hui DS, Azhar EI, Kim YJ, Memish ZA, Oh MD, Zumla A. 2018. Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission. Lancet Infect Dis 18:e217–e227.
    92.
    Kritas SK, Ronconi G, Caraffa A, Gallenga CE, Ross R, Conti P. 4 February 2020. Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents doi:
    93.
    WHO. 2003. Consensus document on the epidemiology of severe acute respiratory syndrome (SARS). https://www.who.int/csr/sars/en/WHOconsensus.pdf. Accessed 29 January 2020.
    94.
    Donnelly CA, Ghani AC, Leung GM, Hedley AJ, Fraser C, Riley S, Abu-Raddad LJ, Ho LM, Thach TQ, Chau P, Chan KP, Lam TH, Tse LY, Tsang T, Liu SH, Kong JH, Lau EM, Ferguson NM, Anderson RM. 2003. Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet 361:1761–1766.
    95.
    Millan-Oñate J, Rodríguez-Morales AJ, Camacho-Moreno G, Mendoza-Ramírez H, Rodríguez-Sabogal IA, Álvarez-Moreno C. 2020. A new emerging zoonotic virus of concern: the 2019 novel coronavirus (COVID-19). Infect 24:187.
    96.
    Wilder-Smith A, Freedman DO. 2020. Isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV) outbreak. J Travel Med 27:taaa020.
    97.
    WHO. 2019. Middle East respiratory syndrome coronavirus (MERS-CoV). https://www.who.int/en/news-room/fact-sheets/detail/middle-east-respiratory-syndromecoronavirus-(mers-cov). Accessed 29 January 2020.
    98.
    Jiang X, Rayner S, Luo MH. 2020. Does SARS-CoV-2 has a longer incubation period than SARS and MERS? J Med Virol 92:476–478.
    99.
    Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E. 2020. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res 176:104742.
    100.
    Angeletti S, Benvenuto D, Bianchi M, Giovanetti M, Pascarella S, Ciccozzi M. 2020. COVID-2019: the role of the nsp2 and nsp3 in its pathogenesis. J Med Virol 92:584–588.
    101.
    Mahase E. 2020. Coronavirus Covid-19 has killed more people than SARS and MERS combined, despite lower case fatality rate. BMJ 368:m641.
    102.
    Song Z, Xu Y, Bao L, Zhang L, Yu P, Qu Y, Zhu H, Zhao W, Han Y, Qin C. 2019. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses 11:59.
    103.
    Perlman S. 2020. Another decade, another coronavirus. N Engl J Med 382:10.1056/NEJMe2001126-762.
    104.
    Graham RL, Donaldson EF, Baric RS. 2013. A decade after SARS: strategies for controlling emerging coronaviruses. Nat Rev Microbiol 11:836–848.
    105.
    Menachery VD, Yount BL, Jr, Debbink K, Agnihothram S, Gralinski LE, Plante JA, Graham RL, Scobey T, Ge XY, Donaldson EF, Randell SH, Lanzavecchia A, Marasco WA, Shi ZL, Baric RS. 2015. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat Med 21:1508–1513.
    106.
    Cui J, Li F, Shi ZL. 2019. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 17:181–192.
    107.
    Lau SKP, Luk HKH, Wong ACP, Fan RYY, Lam CSF, Li KSM, Ahmed SS, Chow FWN, Cai JP, Zhu X, Chan JFW, Lau TCK, Cao K, Li M, Woo PCY, Yuen KY. 2019. Identification of a novel betacoronavirus (Merbecovirus) in amur hedgehogs from China. Viruses 11:980.
    108.
    WHO. 2018. WHO MERS global summary and assessment of risk, August 2018. https://www.who.int/csr/disease/coronavirus_infections/risk-assessment-august-2018.pdf. Accessed 29 January 2020.
    109.
    Vergara-Alert J, van den Brand JM, Widagdo W, Muñoz M, V, Raj S, Schipper D, Solanes D, Cordón I, Bensaid A, Haagmans BL, Segalés J. 2017. Livestock susceptibility to infection with Middle East respiratory syndrome coronavirus. Emerg Infect Dis 23:232–240.
    110.
    Wu YC, Chen CS, Chan YJ. 2020. Overview of the 2019 novel coronavirus (2019-nCoV): the pathogen of severe specific contagious pneumonia (SSCP). J Chin Med Assoc 83:217–220.
    111.
    Tian HY. 2020. 2019-nCoV: new challenges from coronavirus. Zhonghua Yu Fang Yi Xue Za Zhi 54:E001.
    112.
    Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY. 2020. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 395:514–523.
    113.
    Backer JA, Klinkenberg D, Wallinga J. 2020. Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020. Euro Surveill 25:2000062.
    114.
    Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, Ren R, Leung KSM, Lau EHY, Wong JY, Xing X, Xiang N, Wu Y, Li C, Chen Q, Li D, Liu T, Zhao J, Li M, Tu W, Chen C, Jin L, Yang R, Wang Q, Zhou S, Wang R, Liu H, Luo Y, Liu Y, Shao G, Li H, Tao Z, Yang Y, Deng Z, Liu B, Ma Z, Zhang Y, Shi G, Lam TTY, Wu JTK, Gao GF, Cowling BJ, Yang B, Leung GM, Feng Z. 2020. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 382:1199–1207.
    115.
    Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A, Flemban H, Al-Nassir WN, Balkhy HH, Al-Hakeem RF, Makhdoom HQ, Zumla AI, Memish ZA. 2013. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis 13:752–761.
    116.
    Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. 2020. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395:497–506.
    117.
    Bonilla-Aldana DK, Quintero-Rada K, Montoya-Posada JP, Ramirez-Ocampo S, Paniz-Mondolfi A, Rabaan AA, Sah R, Rodriguez-Morales AJ. 2020. SARS-CoV, MERS-CoV and now the 2019-novel CoV: have we investigated enough about coronaviruses? A bibliometric analysis. Travel Med Infect Dis 33:101566.
    118.
    Zhou L, Liu HG. 2020. Early detection and disease assessment of patients with novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi 43:E003.
    119.
    Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang F-S. 2020. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 8:420–422.
    120.
    Schwartz DA, Graham AL. 2020. Potential maternal and infant outcomes from (Wuhan) coronavirus 2019-nCoV infecting pregnant women: lessons from SARS, MERS, and other human coronavirus infections. Viruses 12:194.
    121.
    Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, Wang Z, Li J, Li J, Feng C, Zhang Z, Wang L, Peng L, Chen L, Qin Y, Zhao D, Tan S, Yin L, Xu J, Zhou C, Jiang C, Liu L. 2020. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. 63:364–374. Sci China Life Sci doi:
    122.
    Qiu HB, Li XY, Du B, Kang HYJ, Wang YS, Wang F, Sun B, Tong ZH. 2020. The keypoints in treatment of the critical novel coronavirus pneumonia patient. Zhonghua Jie He He Hu Xi Za Zhi 43:E022.
    123.
    Guan GW, Gao L, Wang JW, Wen XJ, Mao TH, Peng SW, Zhang T, Chen XM, Lu FM. 2020. Exploring the mechanism of liver enzyme abnormalities in patients with novel coronavirus-infected pneumonia. Zhonghua Gan Zang Bing Za Zhi 28:E002.
    124.
    MacLachlan NJ, Dubovi EJ. 2017. Fenner’s veterinary virology, 5th ed. Academic Press, New York, NY.
    125.
    Gouilh M, Puechmaille SJ, Diancourt L, Vandenbogaert M, Serra-Cobo J, Lopez Roïg M, Brown P, Moutou F, Caro V, Vabret A, Manuguerra J-C, EPICOREM Consortium. 2018. SARS-CoV related Betacoronavirus and diverse Alphacoronavirus members found in western old-world. Virology 517:88–97.
    126.
    Suzuki T, Otake Y, Uchimoto S, Hasebe A, Goto Y. 2020. Genomic characterization and phylogenetic classification of bovine coronaviruses through whole genome sequence analysis. Viruses 12:183.
    127.
    Zhang XM, Herbst W, Kousoulas KG, Storz J. 1994. Biological and genetic characterization of a hemagglutinating coronavirus isolated from a diarrhoeic child. J Med Virol 44:152–161.
    128.
    Tekes G, Thiel HJ. 2016. Feline coronaviruses: pathogenesis of feline infectious peritonitis. Adv Virus Res 96:193–218.
    129.
    Licitra BN, Duhamel GE, Whittaker GR. 2014. Canine enteric coronaviruses: emerging viral pathogens with distinct recombinant spike proteins. Viruses 6:3363–3376.
    130.
    Erles K, Brownlie J. 2008. Canine respiratory coronavirus: an emerging pathogen in the canine infectious respiratory disease complex. Vet Clin North Am Small Anim Pract 38:815–825.
    131.
    Dhama K, Singh SD, Barathidasan R, Desingu PA, Chakraborty S, Tiwari R, Kumar MA. 2014. Emergence of avian infectious bronchitis virus and its variants need better diagnosis, prevention and control strategies: a global perspective. Pak J Biol Sci 17:751–767.
    132.
    Bande F, Arshad SS, Omar AR, Bejo MH, Abubakar MS, Abba Y. 2016. Pathogenesis and diagnostic approaches of avian infectious bronchitis. Adv Virol 2016:4621659.
    133.
    Wege H, Siddell S, ter Meulen V. 1982. The biology and pathogenesis of coronaviruses. Curr Top Microbiol Immunol 99:165–200.
    134.
    Zhou P, Fan H, Lan T, Yang XL, Shi WF, Zhang W, Zhu Y, Zhang YW, Xie QM, Mani S, Zheng XS, Li B, Li JM, Guo H, Pei GQ, An XP, Chen JW, Zhou L, Mai KJ, Wu ZX, Li D, Anderson DE, Zhang LB, Li SY, Mi ZQ, He TT, Cong F, Guo PJ, Huang R, Luo Y, Liu XL, Chen J, Huang Y, Sun Q, Zhang XL, Wang YY, Xing SZ, Chen YS, Sun Y, Li J, Daszak P, Wang LF, Shi ZL, Tong YG, Ma JY. 2018. Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin. Nature 556:255–258.
    135.
    Lau SK, Woo PC, Li KS, Huang Y, Wang M, Lam CS, Xu H, Guo R, Chan KH, Zheng BJ, Yuen KY. 2007. Complete genome sequence of bat coronavirus HKU2 from Chinese horseshoe bats revealed a much smaller spike gene with a different evolutionary lineage from the rest of the genome. Virology 367:428–439.
    136.
    Brown IH. 2001. The pig as an intermediate host for influenza A viruses between birds and humans. Int Congr Ser 1219:173–178.
    137.
    Chen W, Yan M, Yang L, Ding B, He B, Wang Y, Liu X, Liu C, Zhu H, You B, Huang S, Zhang J, Mu F, Xiang Z, Feng X, Wen J, Fang J, Yu J, Yang H, Wang J. 2005. SARS-associated coronavirus transmitted from human to pig. Emerg Infect Dis 11:446–448.
    138.
    Mihindukulasuriya KA, Wu G, St Leger J, Nordhausen RW, Wang D. 2008. Identification of a novel coronavirus from a beluga whale by using a panviral microarray. J Virol 82:5084–5088.
    139.
    Wassenaar TM, Zou Y. 14 February 2020. 2019_nCoV: rapid classification of betacoronaviruses and identification of traditional Chinese medicine as potential origin of zoonotic coronaviruses. Lett Appl Microbiol 70:342–348.
    140.
    Phan T. 2020. Novel coronavirus: from discovery to clinical diagnostics. Infect Genet Evol 79:104211.
    141.
    Li HY, Zhu GJ, Zhang YZ, Zhang LB, Hagan EA, Martinez S, Chmura AA, Francisco L, Tai H, Miller M, Daszak P. 2020. A qualitative study of zoonotic risk factors among rural communities in southern China. Int Health 12:77–85.
    142.
    Bonilla-Aldana DK, Suárez JA, Franco-Paredes C, Vilcarromero S, Mattar S, Gómez-Marín JE, Villamil-Gómez WE, Ruíz-Sáenz J, Cardona-Ospina JA, Idarraga-Bedoya SE, García-Bustos JJ, Jimenez-Posada EV, Rodríguez-Morales AJ. 2019. Brazil burning! What is the potential impact of the Amazon wildfires on vector-borne and zoonotic emerging diseases? A statement from an international experts meeting. Travel Med Infect Dis 31:101474.
    143.
    Ji W, Wang W, Zhao X, Zai J, Li X. 2020. Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human. J Med Virol 92:433–440.
    144.
    Liu P, Chen W, Chen JP. 2019. Viral metagenomics revealed Sendai virus and coronavirus infection of Malayan pangolins (Manisjavanica). Viruses 11:979.
    145.
    Xiao K, Zhai J, Feng Y, Zhou N, Zhang X, Zou JJ, Li N, Guo Y, Li X, Shen X, Zhang Z, Shu F, Huang W, Li Y, Zhang Z, Chen R-A, Wu Y-J, Peng S-M, Huang M, Xie W-J, Cai Q-H, Hou F-H, Liu Y, Chen W, Xiao L, Shen Y. 2020. Isolation and characterization of 2019-nCoV-like coronavirus from Malayan pangolins. bioRxiv https://doi.org/10.1101/2020.02.17.951335.
    146.
    Daszak P, Olival KJ, Li H. 2020. A strategy to prevent future epidemics similar to the 2019-nCoV outbreak. Biosafety Health 2:6–8.
    147.
    Wang N, Li SY, Yang XL, Huang HM, Zhang YJ, Guo H, Luo CM, Miller M, Zhu G, Chmura AA, Hagan E, Zhou JH, Zhang YZ, Wang LF, Daszak P, Shi ZL. 2018. Serological evidence of bat SARS-related coronavirus infection in humans, China. Virol Sin 33:104–107.
    148.
    Gao ZC. 2020. Efficient management of novel coronavirus pneumonia by efficient prevention and control in scientific manner. Zhonghua Jie He He Hu Xi Za Zhi 43:E001.
    149.
    Xiao SY, Wu Y, Liu H. 2020. Evolving status of the 2019 novel coronavirus infection: proposal of conventional serologic assays for disease diagnosis and infection monitoring. J Med Virol 92:464–467.
    150.
    Yu F, Du L, Ojcius DM, Pan C, Jiang S. 2020. Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China. Microbes Infect 22:74–79.
    151.
    Pan Y, Zhang D, Yang P, Poon LLM, Wang Q. 2020. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis 20:411–412.
    152.
    To KK, Tsang OT, Chik-Yan Yip C, Chan KH, Wu TC, Chan JMC, Leung WS, Chik TS, Choi CY, Kandamby DH, Lung DC, Tam AR, Poon RW, Fung AY, Hung IF, Cheng VC, Chan JF, Yuen KY. 12 February 2020. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis doi:
    153.
    Zhang W, Du RH, Li B, Zheng XS, Yang XL, Hu B, Wang YY, Xiao GF, Yan B, Shi ZL, Zhou P. 2020. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect 9:386–389.
    154.
    Xie X, Zhong Z, Zhao W, Zheng C, Wang F, Liu J. 12 February 2020. Chest CT for typical 2019-nCoV pneumonia: relationship to negative RT-PCR testing. Radiology doi:
    155.
    Binnicker MJ. 2020. Emergence of a novel coronavirus disease (COVID-19) and the importance of diagnostic testing: why partnership between clinical laboratories, public health agencies, and industry is essential to control the outbreak. Clin Chem 66:664–666.
    156.
    Chu DKW, Pan Y, Cheng SMS, Hui KPY, Krishnan P, Liu Y, Ng DYM, Wan CKC, Yang P, Wang Q, Peiris M, Poon L. 2020. Molecular diagnosis of a novel coronavirus (2019-nCoV) causing an outbreak of pneumonia. Clin Chem 66:549–555.
    157.
    Cohen J, Kupferschmidt K. 2020. Labs scramble to produce new coronavirus diagnostics. Science 367:727.
    158.
    Zhang J, Zhou L, Yang Y, Peng W, Wang W, Chen X. 2020. Therapeutic and triage strategies for 2019 novel coronavirus disease in fever clinics. Lancet Respir Med 8:e11–e12.
    159.
    Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, Fan Y, Zheng C. 2020. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 20:425–434.
    160.
    Kim H. 2020. Outbreak of novel coronavirus (COVID-19): what is the role of radiologists? Eur Radiol 30:3266–3267.
    161.
    Munjal A, Khandia R, Dhama K, Sachan S, Karthik K, Tiwari R, Malik YS, Kumar D, Singh RK, Iqbal HMN, Joshi SK. 2017. Advances in developing therapies to combat Zika virus: current knowledge and future perspectives. Front Microbiol 8:1469.
    162.
    Dhama K, Karthik K, Khandia R, Chakraborty S, Munjal A, Latheef SK, Kumar D, Ramakrishnan MA, Malik YS, Singh R, Malik SVS, Singh RK, Chaicumpa W. 2018. Advances in designing and developing vaccines, drugs, and therapies to counter Ebola virus. Front Immunol 9:1803.
    163.
    Singh RK, Dhama K, Chakraborty S, Tiwari R, Natesan S, Khandia R, Munjal A, Vora KS, Latheef SK, Karthik K, Singh Malik Y, Singh R, Chaicumpa W, Mourya DT. 2019. Nipah virus: epidemiology, pathology, immunobiology and advances in diagnosis, vaccine designing and control strategies—a comprehensive review. Vet Q 39:26–55.
    164.
    Yang ZY, Kong WP, Huang Y, Roberts A, Murphy BR, Subbarao K, Nabel GJ. 2004. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 428:561–564.
    165.
    Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, Kao RY, Poon LL, Wong CL, Guan Y, Peiris JS, Yuen KY, HKU/UCH SARS Study Group. 2004. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 59:252–256.
    166.
    Kumar V, Jung Y-S, Liang P-H. 2013. Anti-SARS coronavirus agents: a patent review (2008–present). Expert Opin Ther Pat 23:1337–1348.
    167.
    Li E, Yan F, Huang P, Chi H, Xu S, Li G, Liu C, Feng N, Wang H, Zhao Y, Yang S, Xia X. 2020. Characterization of the immune response of MERS-CoV vaccine candidates derived from two different vectors in mice. Viruses 12:125.
    168.
    Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S. 2009. The spike protein of SARS-CoV—a target for vaccine and therapeutic development. Nat Rev Microbiol 7:226–236.
    169.
    Wirblich C, Coleman CM, Kurup D, Abraham TS, Bernbaum JG, Jahrling PB, Hensley LE, Johnson RF, Frieman MB, Schnell MJ. 2017. One-health: a safe, efficient, dual-use vaccine for humans and animals against Middle East Respiratory syndrome coronavirus and rabies virus. J Virol 91:e02040-16.
    170.
    Buchholz UJ, Bukreyev A, Yang L, Lamirande EW, Murphy BR, Subbarao K, Collins PL. 2004. Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc Natl Acad Sci U S A 101:9804–9809.
    171.
    Chen R, Fu J, Hu J, Li C, Zhao Y, Qu H, Wen X, Cao S, Wen Y, Wu R, Zhao Q, Yan Q, Huang Y, Ma X, Han X, Huang X. 2020. Identification of the immunodominant neutralizing regions in the spike glycoprotein of porcine deltacoronavirus. Virus Res 276:197834.
    172.
    Liu WJ, Zhao M, Liu K, Xu K, Wong G, Tan W, Gao GF. 2017. T-cell immunity of SARS-CoV: implications for vaccine development against MERS-CoV. Antiviral Res 137:82–92.
    173.
    Jiang S, Du L, Shi Z. 2020. An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies. Emerg Microbes Infect 9:275–277.
    174.
    Veljkovic V, Vergara-Alert J, Segalés J, Paessler S. 2020. Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target. F1000Res 9:52.
    175.
    Jiang S, He Y, Liu S. 2005. SARS vaccine development. Emerg Infect Dis 11:1016–1020.
    176.
    Baruah V, Bose S. 2020. Immunoinformatics-aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019-nCoV. J Med Virol 92:495–500.
    177.
    Kim MH, Kim HJ, Chang J. 2019. Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length spike protein of Middle East respiratory syndrome coronavirus. PLoS One 14:e0220196.
    178.
    Shi J, Zhang J, Li S, Sun J, Teng Y, Wu M, Li J, Li Y, Hu N, Wang H, Hu Y. 2015. Epitope-based vaccine target screening against highly pathogenic MERS-CoV: an in silico approach applied to emerging infectious diseases. PLoS One 10:e0144475.
    179.
    Xie Q, He X, Yang F, Liu X, Li Y, Liu Y, Yang Z, Yu J, Zhang B, Zhao W. 2018. Analysis of the genome sequence and prediction of B-cell epitopes of the envelope protein of Middle East respiratory syndrome-coronavirus. IEEE/ACM Trans Comput Biol Bioinform 15:1344–1350.
    180.
    NIAID. 2020. Developing therapeutics and vaccines for coronaviruses. https://www.niaid.nih.gov/diseases-conditions/coronaviruses-therapeutics-vaccines. Accessed 15 February 2020.
    181.
    CEPI. 2020. CEPI to fund three programmes to develop vaccines against the novel coronavirus, nCoV-2019. https://cepi.net/news_cepi/cepi-to-fund-three-programmes-to-develop-vaccines-against-the-novel-coronavirus-ncov-2019/. Accessed 15 February 2020.
    182.
    Moderna. 2020. Moderna announces funding award from CEPI to accelerate development of messenger RNA (mRNA) vaccine against novel coronavirus. https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-funding-award-cepi-accelerate-development. Accessed 15 February 2020.
    183.
    Adedeji AO, Severson W, Jonsson C, Singh K, Weiss SR, Sarafianos SG. 2013. Novel inhibitors of severe acute respiratory syndrome coronavirus entry that act by three distinct mechanisms. J Virol 87:8017–8028.
    184.
    Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, Scott DP, Brining D, Bushmaker T, Martellaro C, Baseler L, Benecke AG, Katze MG, Munster VJ, Feldmann H. 2013. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med 19:1313–1317.
    185.
    Lu L, Liu Q, Du L, Jiang S. 2013. Middle East respiratory syndrome coronavirus (MERS-CoV): challenges in identifying its source and controlling its spread. Microbes Infect 15:625–629.
    186.
    Dhama K, Sharun K, Tiwari R, Dadar M, Malik YS, Singh KP, Chaicumpa W. 18 March 2020. COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics. Hum Vaccin Immunother doi:
    187.
    Li H, Wang YM, Xu JY, Cao B. 2020. Potential antiviral therapeutics for 2019 novel coronavirus. Zhonghua Jie He He Hu Xi Za Zhi 43:E002.
    188.
    Wang C, Horby PW, Hayden FG, Gao GF. 2020. A novel coronavirus outbreak of global health concern. Lancet 395:470–473.
    189.
    Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. 2016. Coronaviruses—drug discovery and therapeutic options. Nat Rev Drug Discov 15:327–347.
    190.
    Chan JF, Yao Y, Yeung ML, Deng W, Bao L, Jia L, Li F, Xiao C, Gao H, Yu P, Cai JP, Chu H, Zhou J, Chen H, Qin C, Yuen KY. 2015. Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common Marmoset. J Infect Dis 212:1904–1913.
    191.
    Arabi YM, Alothman A, Balkhy HH, Al-Dawood A, AlJohani S, Al Harbi S, Kojan S, Al Jeraisy M, Deeb AM, Assiri AM, Al-Hameed F, AlSaedi A, Mandourah Y, Almekhlafi GA, Sherbeeni NM, Elzein FE, Memon J, Taha Y, Almotairi A, Maghrabi KA, Qushmaq I, Al Bshabshe A, Kharaba A, Shalhoub S, Jose J, Fowler RA, Hayden FG, Hussein MA, MIRACLE Trial Group. 2018. Treatment of Middle East respiratory syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials 19:81.
    192.
    WHO. 2020. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. Available on https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected. Accessed on 7 February 2020.
    193.
    Wang Z, Chen X, Lu Y, Chen F, Zhang W. 2020. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Biosci Trends 14:64–68.
    194.
    Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. 2020. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30:269–271.
    195.
    Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, Leist SR, Pyrc K, Feng JY, Trantcheva I, Bannister R, Park Y, Babusis D, Clarke MO, Mackman RL, Spahn JE, Palmiotti CA, Siegel D, Ray AS, Cihlar T, Jordan R, Denison MR, Baric RS. 2017. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med 9:eaal3653.
    196.
    Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, Seidah NG, Nichol ST. 2005. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2:69.
    197.
    Gao J, Tian Z, Yang X. 2020. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 14:72–73.
    198.
    Widjaja I, Wang C, van Haperen R, Gutiérrez-Álvarez J, van Dieren B, Okba NMA, Raj VS, Li W, Fernandez-Delgado R, Grosveld F, van Kuppeveld FJM, Haagmans BL, Enjuanes L, Drabek D, Bosch BJ. 2019. Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein. Emerg Microbes Infect 8:516–530.
    199.
    Goo J, Jeong Y, Park Y-S, Yang E, Jung D-I, Rho S, Park U, Sung H, Park P-G, Choi J-A, Seo SH, Cho NH, Lee H, Lee JM, Kim J-O, Song M. 2020. Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein. Virus Res 278:197863.
    200.
    Zeng LP, Ge XY, Peng C, Tai W, Jiang S, Du L, Shi ZL. 2017. Cross-neutralization of SARS coronavirus-specific antibodies against bat SARS-like coronaviruses. Sci China Life Sci 60:1399–1402.
    201.
    Cohen J. 2020. New coronavirus threat galvanizes scientists. Science 367:492–493.
    202.
    Tian X, Li C, Huang A, Xia S, Lu S, Shi Z, Lu L, Jiang S, Yang Z, Wu Y, Ying T. 2020. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect 9:382–385.
    203.
    Kilianski A, Baker SC. 2014. Cell-based antiviral screening against coronaviruses: developing virus-specific and broad-spectrum inhibitors. Antiviral Res 101:105–112.
    204.
    Zhao J, Perera RA, Kayali G, Meyerholz D, Perlman S, Peiris M. 2015. Passive immunotherapy with dromedary immune serum in an experimental animal model for Middle East respiratory syndrome coronavirus infection. J Virol 89:6117–6120.
    205.
    Zhang L, Liu Y. 2020. Potential interventions for novel coronavirus in China: a systemic review. J Med Virol 92:479–490.
    206.
    Seesuay W, Jittavisutthikul S, Sae-Lim N, Sookrung N, Sakolvaree Y, Chaicumpa W. 2018. Human transbodies that interfere with the functions of Ebola virus VP35 protein in genome replication and transcription and innate immune antagonism. Emerg Microbes Infect 7:41.
    207.
    Sun ML, Yang JM, Sun YP, Su GH. 2020. Inhibitors of RAS might be a good choice for the therapy of COVID-19 pneumonia. Zhonghua Jie He He Hu Xi Za Zhi 43:E014.
    208.
    de Wilde AH, Jochmans D, Posthuma CC, Zevenhoven-Dobbe JC, van Nieuwkoop S, Bestebroer TM, van den Hoogen BG, Neyts J, Snijder EJ. 2014. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother 58:4875–4884.
    209.
    Liu J, Zheng X, Tong Q, Li W, Wang B, Sutter K, Trilling M, Lu M, Dittmer U, Yang D. 2020. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. J Med Virol 92:491–494.
    210.
    Xia S, Zhu Y, Liu M, Lan Q, Xu W, Wu Y, Ying T, Liu S, Shi Z, Jiang S, Lu L. 11 February 2020. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell Mol Immunol doi:
    211.
    Gretebeck LM, Subbarao K. 2015. Animal models for SARS and MERS coronaviruses. Curr Opin Virol 13:123–129.
    212.
    Yong CY, Ong HK, Yeap SK, Ho KL, Tan WS. 2019. Recent advances in the vaccine development against Middle East respiratory syndrome-coronavirus. Front Microbiol 10:1781.
    213.
    Martina BE, Haagmans BL, Kuiken T, Fouchier RA, Rimmelzwaan GF, Van Amerongen G, Peiris JS, Lim W, Osterhaus AD. 2003. Virology: SARS virus infection of cats and ferrets. Nature 425:915.
    214.
    Lamirande EW, DeDiego ML, Roberts A, Jackson JP, Alvarez E, Sheahan T, Shieh WJ, Zaki SR, Baric R, Enjuanes L, Subbarao K. 2008. A live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden Syrian hamsters. J Virol 82:7721–7724.
    215.
    Roberts A, Lamirande EW, Vogel L, Jackson JP, Paddock CD, Guarner J, Zaki SR, Sheahan T, Baric R, Subbarao K. 2008. Animal models and vaccines for SARS-CoV infection. Virus Res 133:20–32.
    216.
    Falzarano D, de Wit E, Feldmann F, Rasmussen AL, Okumura A, Peng X, Thomas MJ, van Doremalen N, Haddock E, Nagy L, LaCasse R, Liu T, Zhu J, McLellan JS, Scott DP, Katze MG, Feldmann H, Munster VJ. 2014. Infection with MERS-CoV causes lethal pneumonia in the common marmoset. PLoS Pathog 10:e1004250.
    217.
    Du L, Tai W, Zhou Y, Jiang S. 2016. Vaccines for the prevention against the threat of MERS-CoV. Expert Rev Vaccines 15:1123–1134.
    218.
    Enjuanes L, Zuñiga S, Castaño-Rodriguez C, Gutierrez-Alvarez J, Canton J, Sola I. 2016. Molecular basis of coronavirus virulence and vaccine development. Adv Virus Res 96:245–286.
    219.
    Yang XH, Deng W, Tong Z, Liu YX, Zhang LF, Zhu H, Gao H, Huang L, Liu YL, Ma CM, Xu YF, Ding MX, Deng HK, Qin C. 2007. Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection. Comp Med 57:450–459.
    220.
    Leist SR, Cockrell AS. 2020. Genetically engineering a susceptible mouse model for MERS-CoV-induced acute respiratory distress syndrome. Methods Mol Biol 2099:137–159.
    221.
    Zhou Y, Jiang S, Du L. 2018. Prospects for a MERS-CoV spike vaccine. Expert Rev Vaccines 17:677–686.
    222.
    Cockrell AS, Yount BL, Scobey T, Jensen K, Douglas M, Beall A, Tang XC, Marasco WA, Heise MT, Baric RS. 2016. A mouse model for MERS coronavirus-induced acute respiratory distress syndrome. Nat Microbiol 2:16226.
    223.
    Eckerle I, Corman VM, Müller MA, Lenk M, Ulrich RG, Drosten C. 2014. Replicative capacity of MERS coronavirus in livestock cell lines. Emerg Infect Dis 20:276–279.
    224.
    Milewska A, Nowak P, Owczarek K, Szczepanski A, Zarebski M, Hoang A, Berniak K, Wojarski J, Zeglen S, Baster Z, Rajfur Z, Pyrc K. 2017. Entry of human coronavirus NL63 into the cell. J Virol 92:e01933-17.
    225.
    Nkengasong J. 2020. China’s response to a novel coronavirus stands in stark contrast to the 2002 SARS outbreak response. Nat Med 26:310–311.
    226.
    Khan S, Ali A, Siddique R, Nabi G. 2020. Novel coronavirus is putting the whole world on alert. J Hosp Infect 104:252–253.
    227.
    Sun K, Chen J, Viboud C. 2020. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study. Lancet Digital Health 2:e201–e208.
    228.
    Tang B, Wang X, Li Q, Bragazzi NL, Tang S, Xiao Y, Wu J. 2020. Estimation of the transmission risk of the 2019-nCoV and its implication for public health interventions. J Clin Med 9:462.
    229.
    Kang L, Li Y, Hu S, Chen M, Yang C, Yang BX, Wang Y, Hu J, Lai J, Ma X, Chen J, Guan L, Wang G, Ma H, Liu Z. 2020. The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirus. Lancet Psychiatry 7:e14.
    230.
    Guan W, Xian J. 2020. The progress of 2019 novel coronavirus (2019-nCoV) event in China. J Med Virol 92:468–472.
    231.
    Wu JT, Leung K, Leung GM. 2020. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet 395:689–697.
    232.
    Kickbusch I, Leung G. 2020. Response to the emerging novel coronavirus outbreak. BMJ 368:m406.
    233.
    Bogoch II, Watts A, Thomas-Bachli A, Huber C, Kraemer MUG, Khan K. 2020. Potential for global spread of a novel coronavirus from China. J Travel Med 27:taaa011.
    234.
    Khan S, Siddique R, Ali A, Xue M, Nabi G. 2020. Novel coronavirus, poor quarantine, and the risk of pandemic. J Hosp Infect 104:449–450.
    235.
    Thompson RN. 2020. Novel Coronavirus outbreak in Wuhan, China, 2020: intense surveillance is vital for preventing sustained transmission in new locations. J Clin Med 9:498.
    236.
    Du Z, Wang L, Cauchemez S, Xu X, Wang X, Cowling BJ, Meyers LA. 2020. Risk for transportation of 2019 novel coronavirus disease from Wuhan to other cities in China. Emerg Infect Dis 26:1049–1052.
    237.
    Wood C. 2020. Infections without borders: a new coronavirus in Wuhan, China. Br J Nurs 29:166–167.
    238.
    Dong E, Du H, Gardner L. 2020. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 20:533–534.
    239.
    Sawano T, Ozaki A, Rodriguez-Morales AJ, Tanimoto T, Sah R. 2020. Limiting spread of COVID-19 from cruise ships—lessons to be learnt from Japan. QJM 113:309–310.
    240.
    Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, Li J, Zhao D, Xu D, Gong Q, Liao J, Yang H, Hou W, Zhang Y. 2020. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet 395:809–815.
    241.
    Wang X, Zhou Z, Zhang J, Zhu F, Tang Y, Shen X. 28 February 2020. A case of 2019 novel coronavirus in a pregnant woman with preterm delivery. Clin Infect Dis doi:
    242.
    Yu N, Li W, Kang Q, Xiong Z, Wang S, Lin X, Liu Y, Xiao J, Liu H, Deng D, Chen S, Zeng W, Feng L, Wu J. 2020. Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect Dis 20:559–564.
    243.
    Zambrano LI, Fuentes-Barahona IC, Bejarano-Torres DA, Bustillo C, Gonzales G, Vallecillo-Chinchilla G, Sanchez-Martínez FE, Valle-Reconco JA, Sierra M, Bonilla-Aldana DK, Cardona-Ospina JA, Rodríguez-Morales AJ. 25 March 2020. A pregnant woman with COVID-19 in Central America. Travel Med Infect Dis doi:
    244.
    Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, Alvarado-Arnez LE, Bonilla-Aldana DK, Franco-Paredes C, Henao-Martinez AF, Paniz-Mondolfi A, Lagos-Grisales GJ, Ramírez-Vallejo E, Suárez JA, Zambrano LI, Villamil-Gómez WE, Balbin-Ramon GJ, Rabaan AA, Harapan H, Dhama K, Nishiura H, Kataoka H, Ahmad T, Sah R, Latin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19). 2020. Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis. Travel Med Infect Dis 34:101623.
    245.
    Xie C, Jiang L, Huang G, Pu H, Gong B, Lin H, Ma S, Chen X, Long B, Si G, Yu H, Jiang L, Yang X, Shi Y, Yang Z. 2020. Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests. Int J Infect Dis 93:264–267.
    246.
    Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, Tan W. 11 March 2020. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA doi:
    247.
    Kam K-Q, Yung CF, Cui L, Lin RTP, Mak TM, Maiwald M, Li J, Chong CY, Nadua K, Tan NWH, Thoon KC. 28 February 2020. A well infant with coronavirus disease 2019 with high viral load. Clin Infect Dis doi:
    248.
    Woelfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Mueller MA, Niemeyer D, Vollmar P, Rothe C, Hoelscher M, Bleicker T, Bruenink T, Schneider J, Ehmann R, Zwirglmaier K, Drosten C, Wendtner C. 2020. Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster. medRxiv https://doi.org/10.1101/2020.03.05.20030502.
    249.
    He Y, Wang Z, Li F, Shi Y. 2020. Public health might be endangered by possible prolonged discharge of SARS-CoV-2 in stool. J Infect 80:e18–e19.
    250.
    Ianiro G, Mullish BH, Kelly CR, Sokol H, Kassam Z, Ng S, Fischer M, Allegretti JR, Masucci L, Zhang F, Keller J, Sanguinetti M, Costello SP, Tilg H, Gasbarrini A, Cammarota G. 2020. Screening of faecal microbiota transplant donors during the COVID-19 outbreak: suggestions for urgent updates from an international expert panel. Lancet Gastroenterol Hepatol 5:430–432.
    251.
    Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. 2020. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology 158:1831–1833.
    252.
    Yeo C, Kaushal S, Yeo D. 2020. Enteric involvement of coronaviruses: is faecal-oral transmission of SARS-CoV-2 possible? Lancet Gastroenterol Hepatol 5:335–337.
    253.
    Kim JY, Ko JH, Kim Y, Kim YJ, Kim JM, Chung YS, Kim HM, Han MG, Kim SY, Chin BS. 2020. Viral load kinetics of SARS-CoV-2 infection in first two patients in Korea. J Korean Med Sci 35:e86.
    254.
    Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu N-H, Nitsche A, Müller MA, Drosten C, Pöhlmann S. 2020. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181:271–280.
    255.
    Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. 2020. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181:281–292.
    256.
    Su YC, Anderson DE, Young BE, Zhu F, Linster M, Kalimuddin S, Low JGH, Yan Z, Jayakumar J, Sun L, Yan GZ, Mendenhall IH, Leo Y-S, Lye DC, Wang L-F, Smith G. 2020. Discovery of a 382-nt deletion during the early evolution of SARS-CoV-2. bioRxiv https://doi.org/10.1101/2020.04.17.20069641.
    257.
    van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, Tamin A, Harcourt JL, Thornburg NJ, Gerber SI, Lloyd-Smith JO, de Wit E, Munster VJ. 2020. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med 382:1564–1567.
    258.
    Loeffelholz MJ, Tang YW. 2020. Laboratory diagnosis of emerging human coronavirus infections—the state of the art. Emerg Microbes Infect 9:1–26.
    259.
    US Food and Drug Administration. 2020. Coronavirus disease (COVID-19) Emergency Use Authorization (EUA) information—in vitro diagnostic EUAs. https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#covid19ivd.
    260.
    Wang C, Liu Z, Chen Z, Huang X, Xu M, He T, Zhang Z. 2020. The establishment of reference sequence for SARS-CoV-2 and variation analysis. J Med Virol 92:667–674.
    261.
    Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. 2020. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents 55:105932.
    262.
    Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. 2020. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. Crit Care 57:279–283.
    263.
    Devaux CA, Rolain JM, Colson P, Raoult D. 2020. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents 55:105938.
    264.
    Sahraei Z, Shabani M, Shokouhi S, Saffaei A. 2020. Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine. Int J Antimicrob Agents 55:105945.
    265.
    Touret F, de Lamballerie X. 2020. Of chloroquine and COVID-19. Antiviral Res 177:104762.
    266.
    Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. 9 March 2020. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis doi:
    267.
    Zhou D, Dai SM, Tong Q. 20 March 2020. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother doi:
    268.
    Srinivasa A, Tosounidou S, Gordon C. 2017. Increased incidence of gastrointestinal side effects in patients taking hydroxychloroquine: a brand-related issue? J Rheumatol 44:398.
    269.
    U.S. National Library of Medicine. 2020. Clinical trials registry–chloroquine. COVID-19. https://www.clinicaltrials.gov/ct2/results?cond=COVID-19&term=Chloroquine&cntry=&state=&city=&dist=2020.
    270.
    Multicenter Collaboration Group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for Chloroquine in the Treatment of Novel Coronavirus. 2020. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi 43:185–188.
    271.
    Gautret P, Lagier J-C, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Dupont HT, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D. 20 March 2020. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents doi:
    272.
    Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M. 2004. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun 323:264–268.
    273.
    Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. 2020. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 382:1787–1799.
    274.
    Bao L, Deng W, Gao H, Xiao C, Liu J, Xue J, Lv Q, Liu J, Yu P, Xu Y, Qi F, Qu Y, Li F, Xiang Z, Yu H, Gong S, Liu M, Wang G, Wang S, Song Z, Zhao W, Han Y, Zhao L, Liu X, Wei Q, Qin C. 2020. Reinfection could not occur in SARS-CoV-2 infected rhesus macaques. bioRxiv https://doi.org/10.1101/2020.03.13.990226.
    275.
    Cheng VC, Lau SK, Woo PC, Yuen KY. 2007. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin Microbiol Rev 20:660–694.
    276.
    Ison MG, Hirsch HH. 2019. Community-acquired respiratory viruses in transplant patients: diversity, impact, unmet clinical needs. Clin Microbiol Rev 32:e00042-19.
    277.
    Sanchez JL, Cooper MJ, Myers CA, Cummings JF, Vest KG, Russell KL, Sanchez JL, Hiser MJ, Gaydos CA. 2015. Respiratory infections in the U.S. military: recent experience and control. Clin Microbiol Rev 28:743–800.
    278.
    Chan JF, Lau SK, To KK, Cheng VC, Woo PC, Yuen KY. 2015. Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clin Microbiol Rev 28:465–522.
    279.
    Cheng VC, To KK, Tse H, Hung IF, Yuen KY. 2012. Two years after pandemic influenza A/2009/H1N1: what have we learned? Clin Microbiol Rev 25:223–263.
    280.
    Gillim-Ross L, Subbarao K. 2006. Emerging respiratory viruses: challenges and vaccine strategies. Clin Microbiol Rev 19:614–636.
    281.
    Norkin LC. 1995. Virus receptors: implications for pathogenesis and the design of antiviral agents. Clin Microbiol Rev 8:293–315.
    282.
    Dhama K, Patel SK, Pathak M, Yatoo MI, Tiwari R, Malik YS, Singh R, Sah R, Rabaan AA, Bonilla-Aldana DK, Rodriguez-Morales AJ. 2020. An update on SARS-COV-2/COVID-19 with particular reference on its clinical pathology, pathogenesis, immunopathology and mitigation strategies–a review. Preprints https://www.preprints.org/manuscript/202003.0348/v1.
    283.
    Kimberlin DW, Stagno S. 26 March 2020. Can SARS-CoV-2 infection be acquired in utero? More definitive evidence is needed. JAMA doi:
    284.
    Akarsh HP. 2020. Wuhan virus: Chinese animal markets reopened with almost no precautions. https://metrosaga.com/wuhan-virus-chinese-animal-markets-reopened-with-almost-no-precautions/.
    285.
    286.
    Knowles G. 2020. Will they ever learn? Chinese markets are still selling bats and slaughtering rabbits on blood-soaked floors as Beijing celebrates “victory” over the coronavirus. https://www.dailymail.co.uk/news/article-8163761/Chinese-markets-selling-bats.html.
    287.
    Dhama K, Patel SK, Sharun K, Pathak M, Tiwari R, Yatoo MI, Malik YS, Sah R, Rabaan Aa, Panwar Pk, Singh KP, Michalak I, Chaicumpa W, Bonilla-Aldana DK, Rodriguez-Morales AJ. 2020. SARS-CoV-2: jumping the species barrier, lessons from SARS and MERS, its zoonotic spillover, transmission to humans, preventive and control measures and recent developments to counter this pandemic virus. Preprints https://www.preprints.org/manuscript/202004.0011/v1.
    288.
    Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, Ng OT, Marimuthu K, Ang LW, Mak TM, Lau SK, Anderson DE, Chan KS, Tan TY, Ng TY, Cui L, Said Z, Kurupatham L, Chen MI, Chan M, Vasoo S, Wang LF, Tan BH, Lin RTP, Lee VJM, Leo YS, Lye DC, Singapore 2019 Novel Coronavirus Outbreak Research Team. 2020. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA 323:1488.
    289.
    Ong SWX, Tan YK, Chia PY, Lee TH, Ng OT, Wong MSY, Marimuthu K. 2020. Air, surface environmental, and personal protective equipment contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a symptomatic patient. JAMA 323:1610.
    290.
    Zhang T, Cui X, Zhao X, Wang J, Zheng J, Zheng G, Guo W, Cai C, He S, Xu Y. 29 March 2020. Detectable SARS-CoV-2 viral RNA in feces of three children during recovery period of COVID-19 pneumonia. J Med Virol doi:
    291.
    Yu F, Yan L, Wang N, Yang S, Wang L, Tang Y, Gao G, Wang S, Ma C, Xie R, Wang F, Tan C, Zhu L, Guo Y, Zhang F. 28 March 2020. Quantitative detection and viral load analysis of SARS-CoV-2 in infected patients. Clin Infect Dis doi:
    292.
    Huang Y, Cheng W, Zhao N, Qu H, Tian J. 26 March 2020. CT screening for early diagnosis of SARS-CoV-2 infection. Lancet Infect Dis doi:
    293.
    Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, Guo L, Guo R, Chen T, Hu J, Xiang Z, Mu Z, Chen X, Chen J, Hu K, Jin Q, Wang J, Qian Z. 2020. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 11:1620.
    294.
    Ahmed SF, Quadeer AA, McKay MR. 2020. Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies. Viruses 12:254.
    295.
    Ramaiah A, Arumugaswami V. 2020. Insights into cross-species evolution of novel human coronavirus 2019-nCoV and defining immune determinants for vaccine development. bioRxiv https://doi.org/10.1101/2020.01.29.925867.
    296.
    Cohen J. 2020. Vaccine designers take first shots at COVID-19. Science 368:14–16.
    297.
    298.
    WHO. 2020. Draft landscape of COVID-19 candidate vaccines–20 March 2020. https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov.pdf?ua=1.
    299.
    Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. 2020. Features, evaluation and treatment coronavirus (COVID-19). In StatPearls [Internet]. StatPearls Publishing, Treasure Island, FL.
    300.
    Shetty R, Ghosh A, Honavar SG, Khamar P, Sethu S. 2020. Therapeutic opportunities to manage COVID-19/SARS-CoV-2 infection: present and future. Indian J Ophthalmol 68:693.
    301.
    Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, Wang J, Qin Y, Zhang X, Yan X, Zeng X, Zhang S. 2020. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the experience of clinical immunologists from China. Clin Immunol 214:108393.
    302.
    Little P. 2020. Non-steroidal anti-inflammatory drugs and Covid-19. BMJ 368:m1185.
    303.
    Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, Oczkowski S, Levy MM, Derde L, Dzierba A, Du B, Aboodi M, Wunsch H, Cecconi M, Koh Y, Chertow DS, Maitland K, Alshamsi F, Belley-Cote E, Greco M, Laundy M, Morgan JS, Kesecioglu J, McGeer A, Mermel L, Mammen MJ, Alexander PE, Arrington A, Centofanti JE, Citerio G, Baw B, Memish ZA, Hammond N, Hayden FG, Evans L, Rhodes A. 2020. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med 46:854–887.
    304.
    Atluri S, Manchikanti L, Hirsch JA. 2020. Expanded umbilical cord mesenchymal stem cells (UC-MSCs) as a therapeutic strategy in managing critically ill COVID-19 patients: the case for compassionate use. Pain Physician 23:E71–E83.
    305.
    Elfiky AA. 2020. Ribavirin, remdesivir, sofosbuvir, galidesivir, and tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): a molecular docking study. Life Sci 253:117592.
    306.
    Ekins S, Lane TR, Madrid PB. 2020. Tilorone: a broad-spectrum antiviral invented in the USA and commercialized in Russia and beyond. Pharm Res 37:71.
    307.
    Molina JM, Delaugerre C, Goff JL, Mela-Lima B, Ponscarme D, Goldwirt L, de Castro N. 2020. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Med Mal Infect 50:384.
    308.
    Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. 2020. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 178:104787.
    309.
    Ong J, Cross GB, Dan YY. 2020. Prevention of nosocomial SARS-CoV-2 transmission in endoscopy: international recommendations and the need for a gold standard. Gut 69:1145–1148.
    310.
    Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. 2020. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 323:1582.
    311.
    Keith P, Day M, Perkins L, Moyer L, Hewitt K, Wells A. 2020. A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care 24:128.
    312.
    Repici A, Maselli R, Colombo M, Gabbiadini R, Spadaccini M, Anderloni A, Carrara S, Fugazza A, Di Leo M, Galtieri PA, Pellegatta G, Ferrara EC, Azzolini E, Lagioia M. 14 March 2020. Coronavirus (COVID-19) outbreak: what the department of endoscopy should know. Gastrointest Endosc doi:
    313.
    Liu X, Zhang S. 29 March 2020. COVID-19: face masks and human-to-human transmission. Influenza Other Respir Viruses doi:
    314.
    Yang C. 2020. Does hand hygiene reduce SARS-CoV-2 transmission? Graefes Arch Clin Exp Ophthalmol 258:1133–1134.
    315.
    Lai THT, Tang EWH, Fung KSC, Li K. 2020. Reply to “Does hand hygiene reduce SARS-CoV-2 transmission?” Graefes Arch Clin Exp Ophthalmol 258:1135–1135.
    316.
    Chu J, Yang N, Wei Y, Yue H, Zhang F, Zhao J, He L, Sheng G, Chen P, Li G, Wu S, Zhang B, Zhang S, Wang C, Miao X, Li J, Liu W, Zhang H. 29 March 2020. Clinical characteristics of 54 medical staff with COVID-19: a retrospective study in a single center in Wuhan, China. J Med Virol doi:
    317.
    Bonilla-Aldana DK, Dhama K, Rodriguez-Morales AJ. 2020. Revisiting the One Health approach in the context of COVID-19: a look into the ecology of this emerging disease. Adv Anim Vet Sci 8:234–237.
    318.
    Malik YS, Sircar S, Bhat S, Vinodhkumar OR, Tiwari R, Sah R, Rabaan AA, Rodriguez-Morales AJ, Dhama K. 2020. Emerging coronavirus disease (COVID-19), a pandemic public health emergency with animal linkages: current status update. Indian J Anim Sci 90:156–173.
    319.
    Rodriguez-Morales AJ, Tiwari R, Sah R, Dhama K. 2020. COVID-19, an emerging coronavirus infection: current scenario and recent developments—an overview. J Pure Appl Microbiol 14:5–12.
    320.
    Moriarty LF, Plucinski MM, Marston BJ, Kurbatova EV, Knust B, Murray EL, Pesik N, Rose D, Fitter D, Kobayashi M, Toda M, Cantey PT, Scheuer T, Halsey ES, Cohen NJ, Stockman L, Wadford DA, Medley AM, Green G, Regan JJ, Tardivel K, White S, Brown C, Morales C, Yen C, Wittry B, Freeland A, Naramore S, Novak RT, Daigle D, Weinberg M, Acosta A, Herzig C, Kapella BK, Jacobson KR, Lamba K, Ishizumi A, Sarisky J, Svendsen E, Blocher T, Wu C, Charles J, Wagner R, Stewart A, Mead PS, Kurylo E, Campbell S, Murray R, Weidle P, Cetron M, Friedman CR, CDC Cruise Ship Response Team, California Department of Public Health COVID-19 Team, Solano County COVID-19 Team. 2020. Public health responses to COVID-19 outbreaks on cruise ships—worldwide, February–March 2020. MMWR Morb Mortal Wkly Rep 69:347–352.
    321.
    Hasan Z, Narasimhan M. 25 March 2020. Preparing for the COVID-19 pandemic: our experience in New York. Chest doi:
    322.
    Colbourn T. 2020. COVID-19: extending or relaxing distancing control measures. Lancet Public Health 5:e236–e237.
    323.
    Zheng J. 2020. SARS-CoV-2: an emerging coronavirus that causes a global threat. Int J Biol Sci 16:1678–1685.
    324.
    Chatterjee P, Nagi N, Agarwal A, Das B, Banerjee S, Sarkar S, Gupta N, Gangakhedkar RR. 2020. The 2019 novel coronavirus disease (COVID-19) pandemic: a review of the current evidence. Indian J Med Res doi:
    325.
    Xiao DAT, Gao DC, Zhang DS. 21 March 2020. Profile of specific antibodies to SARS-CoV-2: the first report. J Infect doi:
    326.
    Ali M, Zaid M, Saqib MAN, Ahmed H, Afzal MS. 8 April 2020. SARS-CoV-2 and the hidden carriers—sewage, feline, and blood transfusion. J Med Virol doi:
    327.
    Ahmed W, Angel N, Edson J, Bibby K, Bivins A, O'Brien JW, Choi PM, Kitajima M, Simpson SL, Li J, Tscharke B, Verhagen R, Smith WJM, Zaugg J, Dierens L, Hugenholtz P, Thomas KV, Mueller JF. 2020. First confirmed detection of SARS-CoV-2 in untreated wastewater in Australia: a proof of concept for the wastewater surveillance of COVID-19 in the community. Sci Total Environ 728:138764.
    328.
    Núñez-Delgado A. 2020. What do we know about the SARS-CoV-2 coronavirus in the environment? Sci Total Environ 727:138647.
    329.
    Shi J, Wen Z, Zhong G, Yang H, Wang C, Huang B, Liu R, He X, Shuai L, Sun Z, Zhao Y, Liu P, Liang L, Cui P, Wang J, Zhang X, Guan Y, Tan W, Wu G, Chen H, Bu Z. 8 April 2020. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science doi:
    330.
    McNamara T, Richt JA, Glickman L. 2020. A critical needs assessment for research in companion animals and livestock following the pandemic of COVID-19 in humans. Vector Borne Zoonotic Dis 20:393–405.
    331.
    Shanthikumar SR. 2020. We should err on side of caution with Covid-19 advice. Vet Rec 186:458.
    332.
    Li X. 2020. Can cats become infected with Covid-19? Vet Rec 186:457–458.
    333.
    Almendros A, Gascoigne E. 2020. Can companion animals become infected with Covid-19? Vet Rec 186:419–420.
    334.
    IDEXX. 2020. Leading veterinary diagnostic company sees no COVID-19 cases in pets. www.idexx.com/en/about-idexx/news/no-covid-19-cases-pets. Accessed 11 May 2020.
    336.
    Opriessnig T, Huang YW. 2020. Coronavirus disease 2019 (COVID-19) outbreak: could pigs be vectors for human infections? Xenotransplantation 27:e12591.
    337.
    Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, Chang JH, Kim EJ, Lee S, Casel MAB, Um J, Song MS, Jeong HW, Lai VD, Kim Y, Chin BS, Park JS, Chung KH, Foo SS, Poo H, Mo IP, Lee OJ, Webby RJ, Jung JU, Choi YK. 2020. Infection and rapid transmission of SARS-CoV-2 in ferrets. Cell Host Microbe 27:704–709.
    338.
    Sharun K, Shyamkumar TS, Aneesha VA, Dhama K, Pawde AM, Pal A. 2019. Current therapeutic applications and pharmacokinetic modulations of ivermectin. Vet World 12:1204–1211.
    339.
    Patrì A, Fabbrocini G. 2020. Hydroxychloroquine and ivermectin: a synergistic combination for COVID-19 chemoprophylaxis and/or treatment? J Am Acad Dermatol 82:e221.
    340.
    Schmith VD, Zhou JJ, Lohmer LR. 2020. The approved dose of ivermectin alone is not the ideal dose for the treatment of COVID-19. Clin Pharmacol Ther 18:630.
    341.
    Bray M, Rayner C, Noël F, Jans D, Wagstaff K. 2020. Ivermectin and COVID-19: a report in antiviral research, widespread interest, an FDA warning, two letters to the editor and the authors’ responses. Antiviral Res 178:104805.
    342.
    Graham BS. 8 May 2020. Rapid COVID-19 vaccine development. Science doi:
    343.
    Mukherjee R. 2020. Global efforts on vaccines for COVID-19: since, sooner or later, we all will catch the coronavirus. J Biosci 45:68.
    344.
    Abbott. 2020. Abbott launches molecular point-of-care test to detect novel coronavirus in as little as five minutes. https://abbott.mediaroom.com/2020-03-27-Abbott-Launches-Molecular-Point-of-Care-Test-to-Detect-Novel-Coronavirus-in-as-Little-as-Five-Minutes. Accessed 2 April 2020.
    345.
    Ai JW, Zhang Y, Zhang HC, Xu T, Zhang WH. 2020. Era of molecular diagnosis for pathogen identification of unexplained pneumonia, lessons to be learned. Emerg Microbes Infect 9:597–600.
    346.
    Broughton JP, Deng X, Yu G, Fasching CL, Servellita V, Singh J, Miao X, Streithorst JA, Granados A, Sotomayor-Gonzalez A, Zorn K, Gopez A, Hsu E, Gu W, Miller S, Pan CY, Guevara H, Wadford DA, Chen JS, Chiu CY. 16 Apr 2020. CRISPR-Cas12-based detection of SARS-CoV-2. Nat Biotechnol doi:
    347.
    Cheng MP, Papenburg J, Desjardins M, Kanjilal S, Quach C, Libman M, Dittrich S, Yansouni CP. 13 May 2020. Diagnostic testing for severe acute respiratory syndrome-related coronavirus-2: a narrative review. Ann Intern Med 13:M20-1301.
    348.
    Li L, Qin L, Xu Z, Yin Y, Wang X, Kong B, Bai J, Lu Y, Fang Z, Song Q, Cao K, Liu D, Wang G, Xu Q, Fang X, Zhang S, Xia J, Xia J. 19 March 2020. Artificial intelligence distinguishes COVID-19 from community acquired pneumonia on chest CT. Radiology doi:
    349.
    Lu R, Wu X, Wan Z, Li Y, Zuo L, Qin J, Jin X, Zhang C. 1 April 2020. Development of a novel reverse transcription loop-mediated isothermal amplification method for rapid detection of SARS-CoV-2. Virol Sin doi:
    350.
    Pathak M, Patel SK, Jigyasa R, Tiwari R, Dhama K, Sah R, Rabaan AA, Bonilla-Aldana DK, Rodriguez-Morales AJ. 15 April 2020. Global threat of SARS-CoV-2/COVID-19 and the need for more and better diagnostic tools. Arch Med Res doi:
    351.
    Udugama B, Kadhiresan P, Kozlowski HN, Malekjahani A, Osborne M, Li VYC, Chen H, Mubareka S, Gubbay JB, Chan W. 2020. Diagnosing COVID-19: the disease and tools for detection. ACS Nano 14:3822–3835.
    352.
    Vashist SK. 2020. In vitro diagnostic assays for COVID-19: recent advances and emerging trends. Diagnostics 10:202.
    353.
    Yang T, Wang YC, Shen CF, Cheng CM. 2020. Point-of-care RNA-based diagnostic device for COVID-19. Diagnostics 10:165.
    354.
    Yu L, Wu S, Hao X, Li X, Liu X, Ye S, Han H, Dong X, Li X, Li J. 2020. Rapid colorimetric detection of COVID-19 coronavirus using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic plat-form: iLACO. medRxiv https://10.1101/2020.02.20.20025874.
    355.
    Zhang F, Abudayyeh OO, Gootenberg JS. 2020. A protocol for detection of COVID-19 using CRISPR diagnostics. Broad Institute, Cambridge, MA.
    356.
    Arab-Mazar Z, Sah R, Rabaan AA, Dhama K, Rodriguez-Morales AJ. 2020. Mapping the incidence of the COVID-19 hotspot in Iran—implications for travellers. Travel Med Infect Dis 34:101630.
    357.
    Ebrahim SH, Memish ZA. 2020. COVID-19: preparing for superspreader potential among Umrah pilgrims to Saudi Arabia. Lancet 395:e48.
    358.
    Kamel Boulos MN, Geraghty EM. 2020. Geographical tracking and mapping of coronavirus disease COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic and associated events around the world: how 21st century GIS technologies are supporting the global fight against outbreaks and epidemics. Int J Health Geogr 19:8.
    359.
    Lin C, Braund WE, Auerbach J. 2020. Policy decisions and use of information technology to fight 2019 novel coronavirus disease, Taiwan. Emerg Infect Dis doi:
    360.
    Wynants L, Calster BV, Bonten MMJ, Collins GS, Debray TPA, De Vos M, Haller MC, Heinze G, Moons KGM, Riley RD, Schuit E, Smits LJM, Snell KIE, Steyerberg EW, Wallisch C, van Smeden M. 2020. Prediction models for diagnosis and prognosis of Covid-19 infection: systematic review and critical appraisal. BMJ 369:m1328.
    361.
    Whitehead CL, Walker SP. 13 May 2020. Consider pregnancy in COVID-19 therapeutic drug and vaccine trials. Lancet doi:
    362.
    Burton DR, Walker LM. 2020. Rational vaccine design in the time of COVID-19. Cell Host Microbe 27:695–698.
    363.
    O’Connor E, Teh J, Kamat AM, Lawrentschuk N. 14 May 2020. Bacillus Calmette Guérin (BCG) vaccination use in the fight against COVID-19–what’s old is new again? Future Oncol doi:
    364.
    Hamiel U, Kozer E, Youngster I. 13 May 2020. SARS-CoV-2 rates in BCG-vaccinated and unvaccinated young adults. JAMA doi:
    365.
    Ojha R, Gupta N, Naik B, Singh S, Verma VK, Prusty D, Prajapati VK. 14 May 2020. High throughput and comprehensive approach to develop multiepitope vaccine against minacious COVID-19. Eur J Pharm Sci doi:
    366.
    Tang X, Wu C, Li X, Song Y, Yao X, Wu X, Duan Y, Zhang H, Wang Y, Qian Z, Cui J, Lu J. 3 March 2020. On the origin and continuing evolution of SARS-CoV-2. Natl Sci Rev doi:
    367.
    Lockey E. 2020. COVID-19: the race for a vaccine. J Renin Angiotensin Aldosterone Syst 21:1470320320926902.

    Author Bios

    Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
    Kuldeep Dhama, M.V.Sc., Ph.D. (Gold Medalist), is working as Principal Scientist in the Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India. With 25 years of research and teaching experience in the areas of microbiology, immunology, virology, public health, medicine, and biomedicine as an eminent researcher, he has developed several diagnostics, vaccines, immunomodulatory modules, and hypotheses to counter infectious diseases of animals, poultry, and public health concerns. He has to his credit 600 publications, 6 books, and 65 book chapters. Dr. Dhama has been recognized as an extremely productive researcher in the journal Nature. He has been honored with 50 Best Paper Awards and other recognitions. He is an NAAS (National Academy of Agricultural Science, India) Associate and has worked as Nodal Officer, WTO, and Member, Wildlife Health Specialist Group (IUCN). He is actively serving as Editor-in-Chief, Co-EIC, Editor, and Member, Editorial Board, of nearly 20 scientific journals. His Google scholar h-index is 47 and Scopus h-index is 31.
    Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
    Sharun Khan, M.V.Sc., is currently working as a researcher in the Stem Cell Laboratory, Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, India. His area of interest is regenerative medicine with a focus on understanding cell biology and molecular pathways involved in the maintenance and differentiation of stem cells originating from different tissues. He has particular interest and knowledge in the fields of veterinary medicine, pharmacology, infectious diseases of animals, wildlife diseases, diagnosis and therapy of animal diseases, nutrition, and biomedicine. With excellent academic records, he has received awards and recognitions (fellowships and scholarships) and participated in national and international workshops, training programs, and courses. He has a keen interest in learning excellent scientific writing skills and has published 30 papers, including in international journals of repute. He is highly enthusiastic about gaining knowledge of advancements in educational and scientific research areas.
    Ruchi Tiwari
    Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, Uttar Pradesh Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go Anusandhan Sansthan (DUVASU), Mathura, India
    Ruchi Tiwari is currently working as Assistant Professor in the Department of Veterinary Microbiology, College of Veterinary Sciences, DUVASU, Mathura, India. She is currently pursuing her Ph.D. (Hons) degree from DUVASU. With an excellent academic record and 10 years of research and teaching experience, she has expertise in the field of diagnosis, prevention, and control of important livestock/poultry diseases/pathogens having public health significance, along with particular reference to veterinary microbiology, immunology, ethnoveterinary medicine, alternative and complementary therapies, and bacteriophage therapy. Dr. Tiwari has published 150 research/review articles and 5 book chapters. She has been honored with the Young Scientist Award, Best Paper Awards (10), and Outstanding Women Faculty Award (2019). She is serving as Editor and Member, Editorial Board, and Reviewer of 15 international journals. Her Google scholar h-index is 40 and Scopus h-index is 26.
    Division of Biological Standardization, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
    Shubhankar Sircar, a Ph.D. scholar, received his master’s degree from Integral University Lucknow, India, in 2012 and is presently serving as a Senior Research Fellow in an ICAR-National Fellow Scheme in the Division of Biological Standardization at the ICAR-Indian Veterinary Research Institute (IVRI), Izatnagar, India. His area of interest is molecular epidemiology and genotype distribution of major enteric viruses, with a focus on developing different molecular as well as serological diagnostic testing assays. Apart from his expertise in viral diagnosis, he has particular interest and knowledge in the fields of infectious diseases of farms, animals, and wildlife. With good academic records, he has received a few awards and recognitions (Best Poster and Young Scientist) and participated in several national and international workshops, training programs, and conferences. He has published 30 papers in journals of repute. He is highly enthusiastic about gaining knowledge of advancements in educational and scientific research areas.
    Sudipta Bhat
    Division of Biological Standardization, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
    Sudipta Bhat, a Ph.D. scholar, received his bachelor's (B.V.Sc.) from West Bengal University of Animal and Fishery Sciences, Kolkata, India, and masters (M.V.Sc.) from ICAR-Indian Veterinary Research Institute (IVRI), Bareilly, India. He has been pursuing a Ph.D. in Veterinary Virology, ICAR-IVRI, since 2016. He has worked on the highly pathogenic H5N1 avian influenza virus and now is working on emerging enteric viruses of zoonotic importance from different animal species. He has published his research findings in international journals. His area of interest is infectious diseases with a focus on understanding the antigenic and genetic diversity of viruses causing disease of several livestock species. With brilliant academic records, he has also been awarded several fellowships and scholarships and participated in several national and international workshops, training programs, and courses.
    Yashpal Singh Malik
    Division of Biological Standardization, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
    Yashpal Singh Malik, M.V.Sc., Ph.D., serving as an ICAR-National Fellow and Professor, is an expert on enteric viral infections, zoonosis, and emerging viral diseases of animals and humans. He has contributed immensely to viral disease epidemiology, virus-host interactions, microbial biodiversity, characterization, and diagnosis of pathogens. He performed his postdoctoral work at the University of Minnesota. He acquired advanced training in molecular virology from the Division of Virology, University of Ottawa, Canada, and Wuhan Institute of Virology, China. He has represented India in the scientific arena in more than 12 countries. He is the Secretary-General of the Indian Virological Society and Secretary for the World Society for Virology (USA). He is a study group member of the ICTV on Birnaviridae and Picobirnaviridae. He has authored five books from reputed publishers, including Elsevier and Springer Nature, and has published 225 scientific research articles and reviews in journals of high impact factor. His h-index is 29, and his RG score is 39.
    Karam Pal Singh
    Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
    Karam Pal Singh, Ph.D., obtained his B.V.Sc. and A.H. degrees from CSA University of Agriculture & Technology, Kanpur, India, and M.V.Sc. (1987) and Ph.D. (1990) degrees in veterinary pathology from the ICAR-Indian Veterinary Research Institute (IVRI), Izatnagar, India. He worked as Scientist, Senior Scientist, and Principal Scientist before taking charge as the Acting Head, Division of Pathology, on 1 January 2019. He worked at the Institute of Animal Health, Pirbright, United Kingdom, as a visiting fellow from April to December 1996. He worked at the Institute of Animal Health, Pirbright, United Kingdom, as a Postdoctoral Fellow on a Wellcome Trust Fellowship from September 2002 to August 2004. Further, he worked at the Veterinary Research Centre, Muscat, Sultanate of Oman, as an Expert Pathologist from June 2008 to May 2009. Dr. Singh is a veterinary pathologist. His area of interest is infectious diseases with a focus on understanding the pathogenesis and molecular diagnosis of viral diseases, with particular reference to rabies and bluetongue viruses.
    Wanpen Chaicumpa
    Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
    Wanpen Chaicumpa, D.V.M. (Hons.), Ph.D. (microbiology), is Emeritus Professor, Research Consultant, and Head of the Center of Research Excellence on Therapeutic Proteins and Antibody Engineering at the Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, and consultant of the Faculty of Allied Health Sciences, Thammasat University, Thailand. Her research interests are intestinal immunity against enteric infections, vaccine development, immuno- and molecular diagnoses of tropical infections, allergy, immunotherapy, and antibody engineering. She is an executive member of the Thailand Academy of Sciences. She has served as Editor in Chief of the Asian Pacific Journal of Allergy and Immunology. She served as a consultant to the WHO Southeast Asian Regional Office, India. She has published over 250 publications, owns more than 30 patents/patent applications, and has published three textbooks (Animal Viruses, Immunology for Diagnosis of Diseases, and Practical Immunology for Students of Diploma of Tropical Medicines).
    D. Katterine Bonilla-Aldana https://orcid.org/0000-0002-9412-2556
    Semillero de Zoonosis, Grupo de Investigación BIOECOS, Fundación Universitaria Autónoma de las Américas, Sede Pereira, Pereira, Risaralda, Colombia
    Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnologica de Pereira, Pereira, Colombia
    Latin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19), Pereira, Risaralda, Colombia
    D. Katterine Bonilla-Aldana, D.V.M., M.Sc., graduated from Universidad de la Amazonia, School of Veterinary Medicine and Zootechnics, in Florencia, Colombia, in 2015. She completed a master of sciences in microbiology, Universidad Metropolitana, Barranquilla, Colombia, in 2019. She served as a Young Researcher, Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnológica de Pereira (UTP), in Pereira, Risaralda, Colombia. She is a member of the Colombian Infectious Diseases Association (ACIN) and the International Society for Infectious Diseases. She is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of the ACIN. She has been recognized as Junior Researcher, Ministry of Science in Colombia, MinCiencias. She is a Professor of veterinary medicine and zootechnics, Fundación Universitaria Autónoma de las Americas (FUAM), in Pereira, Risaralda, Colombia. She is a Lead Professor of the Zoonoses Research Incubator (SIZOO), FUAM. Her main research interest is the study of zoonotic tick-borne and vector-borne diseases.
    Alfonso J. Rodriguez-Morales https://orcid.org/0000-0001-9773-2192
    Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnologica de Pereira, Pereira, Colombia
    Latin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19), Pereira, Risaralda, Colombia
    Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de las Americas, Pereira, Risaralda, Colombia
    Alfonso J. Rodriguez-Morales, M.D., M.Sc., D.T.M. and H., F.R.S.T.M.H. (Lon), F.F.T.M.R.C.P.S. (Glasg), F.A.C.E., Ph.D.(c), Hon.D.Sc., is an expert in tropical and emerging diseases, particularly in zoonotic and vector-borne diseases. He is President of the Travel Medicine Committee, Pan-American Infectious Diseases Association (API), as well as the Vice President, Colombian Infectious Diseases Association (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine, ACIN. He is part of the Executive Board of the Latin American Society for Travel Medicine (SLAMVI) and of the Council of the International Society for Infectious Diseases. Since 2014, he has been recognized as Senior Researcher, Ministry of Science (MinCiencias), Colombia. He is Professor, Faculty of Health Sciences, Universidad Tecnológica de Pereira, and of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is Codirector of the Public Health and Infection Research Group, UTP, classified A1 by Colciencias. His Scopus H index is 30 (Google scholar H index, 46).

    Information & Contributors

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    Published In

    Clinical Microbiology Reviews
    Volume 33Number 416 September 2020
    eLocator: e00028-20

    History

    Published online: 24 June 2020

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    KEYWORDS

    1. COVID-19
    2. emerging coronavirus
    3. SARS-CoV-2
    4. diagnosis
    5. One Health
    6. therapy
    7. vaccines

    Contributors

    Authors

    Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
    Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
    Ruchi Tiwari
    Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, Uttar Pradesh Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go Anusandhan Sansthan (DUVASU), Mathura, India
    Division of Biological Standardization, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
    Sudipta Bhat
    Division of Biological Standardization, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
    Yashpal Singh Malik
    Division of Biological Standardization, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
    Karam Pal Singh
    Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
    Wanpen Chaicumpa
    Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
    D. Katterine Bonilla-Aldana https://orcid.org/0000-0002-9412-2556
    Semillero de Zoonosis, Grupo de Investigación BIOECOS, Fundación Universitaria Autónoma de las Américas, Sede Pereira, Pereira, Risaralda, Colombia
    Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnologica de Pereira, Pereira, Colombia
    Latin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19), Pereira, Risaralda, Colombia
    Alfonso J. Rodriguez-Morales https://orcid.org/0000-0001-9773-2192
    Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnologica de Pereira, Pereira, Colombia
    Latin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19), Pereira, Risaralda, Colombia
    Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de las Americas, Pereira, Risaralda, Colombia

    Notes

    Address correspondence to Yashpal Singh Malik, [email protected], or Alfonso J. Rodriguez-Morales, [email protected].

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  • Clinical Microbiology ReviewsArticle
    Early-Onset Neonatal Sepsis

    SUMMARY

    Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS.

    REFERENCES

    1.
    Edwards MS and Baker CJ. 2004. Sepsis in the newborn, p 545–561. In Gershon AA, Hotez PJ, and Katz SL (ed), Krugman's infectious diseases of children, 11th ed. Mosby, Philadelphia, PA.
    2.
    Schuchat A. 2000. Neonatal group B streptococcal disease—screening and prevention. N. Engl. J. Med. 343:209–210.
    3.
    Hornik CP, Fort P, Clark RH, Watt K, Benjamin DK Jr, Smith PB, Manzoni P, Jacqz-Aigrain E, Kaguelidou F, and Cohen-Wolkowiez M. 2012. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum. Dev. 88:S69–S74.
    4.
    Edwards MS and Gonik B. 28 November 2012. Preventing the broad spectrum of perinatal morbidity and mortality through group B streptococcal vaccination. Vaccine [Epub ahead of print.].
    5.
    Franciosi RA, Knostman JD, and Zimmerman RA. 1973. Group B streptococcal neonatal and infant infections. J. Pediatr. 82:707–718.
    6.
    Bauserman MS, Laughon MM, Hornik CP, Smith PB, Benjamin DK Jr, Clark RH, Engmann C, and Cohen-Wolkowiez M. 2013. Group B Streptococcus and Escherichia coli infections in the intensive care nursery in the era of intrapartum antibiotic prophylaxis. Pediatr. Infect. Dis. J. 32:208–212.
    7.
    Guilbert J, Levy C, Cohen R, Delacourt C, Renolleau S, and Flamant C. 2010. Late and ultra late onset Streptococcus B meningitis: clinical and bacteriological data over 6 years in France. Acta Paediatr. 99:47–51.
    8.
    Lin TY, Kao HT, Hsieh SH, Huang YC, Chiu CH, Chou YH, Yang PH, Lin RI, Tsao KC, Hsu KH, and Chang LY. 2003. Neonatal enterovirus infections: emphasis on risk factors of severe and fatal infections. Pediatr. Infect. Dis. J. 22:889–894.
    9.
    Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, and Poole WK. 2002. Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants. N. Engl. J. Med. 347:240–247.
    10.
    Cohen-Wolkowiez M, Moran C, Benjamin DK, Cotten CM, Clark RH, Benjamin DK Jr, and Smith PB. 2009. Early and late onset sepsis in late preterm infants. Pediatr. Infect. Dis. J. 28:1052–1056.
    11.
    Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP, Bizzarro MJ, Goldberg RN, Frantz ID III, Hale EC, Shankaran S, Kennedy K, Carlo WA, Watterberg KL, Bell EF, Walsh MC, Schibler K, Laptook AR, Shane AL, Schrag SJ, Das A, Higgins RD, and Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. 2011. Early onset neonatal sepsis: the burden of group B streptococcal and E. coli disease continues. Pediatrics 127:817–826.
    12.
    Weston EJ, Pondo T, Lewis MM, Martell-Cleary P, Morin C, Jewell B, Daily P, Apostol M, Petit S, Farley M, Lynfield R, Reingold A, Hansen NI, Stoll BJ, Shane AJ, Zell E, and Schrag SJ. 2011. The burden of invasive early-onset neonatal sepsis in the United States, 2005-2008. Pediatr. Infect. Dis. J. 30:937–941.
    13.
    Polin RA and St Geme JW III. 1992. Neonatal sepsis. Adv. Pediatr. Infect. Dis. 7:25–61.
    14.
    Gibbs RS and Duff P. 1991. Progress in pathogenesis and management of clinical intraamniotic infection. Am. J. Obstet. Gynecol. 164:1317–1326.
    15.
    Schuchat A, Deaver-Robinson K, Plikaytis BD, Zangwill KM, Mohle-Boetani J, and Wenger JD. 1994. Multistate case-control study of maternal risk factors for neonatal group B streptococcal disease. The Active Surveillance Study Group. Pediatr. Infect. Dis. J. 13:623–629.
    16.
    Adair CE, Kowalsky L, Quon H, Ma D, Stoffman J, McGeer A, Robertson S, Mucenski M, and Davies HD. 2003. Risk factors for early-onset group B streptococcal disease in neonates: a population-based case-control study. CMAJ 169:198–203. http://www.cmaj.ca/content/169/3/198.long.
    17.
    Wood EG and Dillon HC Jr. 1981. A prospective study of group B streptococcal bacteriuria in pregnancy. Am. J. Obstet. Gynecol. 140:515–520.
    18.
    Moller M, Thomsen AC, Borch K, Dinesen K, and Zdravkovic M. 1984. Rupture of fetal membranes and premature delivery associated with group B streptococci in urine of pregnant women. Lancet ii:69–70.
    19.
    Liston TE, Harris RE, Foshee S, and Null DM Jr. 1979. Relationship of neonatal pneumonia to maternal urinary and neonatal isolates of group B streptococci. South. Med. J. 72:1410–1412.
    20.
    Persson K, Christensen KK, Christensen P, Forsgren A, Jorgensen C, and Persson PH. 1985. Asymptomatic bacteriuria during pregnancy with special reference to group B streptococci. Scand. J. Infect. Dis. 17:195–199.
    21.
    Carstensen H, Christensen KK, Grennert L, Persson K, and Polberger S. 1988. Early-onset neonatal group B streptococcal septicaemia in siblings. J. Infect. 17:201–204.
    22.
    Faxelius G, Bremme K, Kvist-Christensen K, Christensen P, and Ringertz S. 1988. Neonatal septicemia due to group B streptococci—perinatal risk factors and outcome of subsequent pregnancies. J. Perinat. Med. 16:423–430.
    23.
    Christensen KK, Dahlander K, Linden V, Svenningsen N, and Christensen P. 1981. Obstetrical care in future pregnancies after fetal loss in group B streptococcal septicemia. A prevention program based on bacteriological and immunological follow-up. Eur. J. Obstet. Gynecol. Reprod. Biol. 12:143–150.
    24.
    Baker CJ and Kasper DL. 1976. Correlation of maternal antibody deficiency with susceptibility to neonatal group B streptococcal infection. N. Engl. J. Med. 294:753–756.
    25.
    Tita AT and Andrews WW. 2010. Diagnosis and management of clinical chorioamnionitis. Clin. Perinatol. 37:339–354.
    26.
    Herbst A and Kallen K. 2007. Time between membrane rupture and delivery and septicemia in term neonates. Obstet. Gynecol. 110:612–618.
    27.
    Polin RA and Committee on Fetus and Newborn. 2012. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics 129:1006–1015.
    28.
    Edwards MS. 2013. Clinical features and diagnosis of sepsis in term and late preterm infants. In Basow DS (ed), UpToDate. UpToDate, Waltham, MA. http://www.uptodate.com/contents/clinical-features-and-diagnosis-of-sepsis-in-term-and-late-preterm-infants?source=search_result&search=neonatal+sepsis&selectedTitle=1∼58. Accessed 11 November 2013.
    29.
    Benitz WE, Gould JB, and Druzin ML. 1999. Risk factors for early-onset group B streptococcal sepsis: estimation of odds ratios by critical literature review. Pediatrics 103:e77.
    30.
    Arnon S and Litmanovitz I. 2008. Diagnostic tests in neonatal sepsis. Curr. Opin. Infect. Dis. 21:223–227.
    31.
    Anderson-Berry A. 2012. Neonatal sepsis. In Medscape reference. WebMD LLC, New York, NY. http://emedicine.medscape.com/article/978352-overview.
    32.
    Hoffman JA, Mason EO, Schutze GE, Tan TQ, Barson WJ, Givner LB, Wald ER, Bradley JS, Yogev R, and Kaplan SL. 2003. Streptococcus pneumoniae infections in the neonate. Pediatrics 112:1095–1102.
    33.
    Bizzarro MJ, Raskind C, Baltimore RS, and Gallagher PG. 2005. Seventy-five years of neonatal sepsis at Yale: 1928-2003. Pediatrics 116:595–602.
    34.
    Stoll BJ, Gordon T, Korones SB, Shankaran S, Tyson JE, Bauer CR, Fanaroff AA, Lemons JA, Donovan EF, Oh W, Stevenson DK, Ehrenkranz RA, Papile LA, Verter J, and Wright LL. 1996. Early-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. J. Pediatr. 129:72–80.
    35.
    Hood M, Janney A, and Dameron G. 1961. Beta hemolytic streptococcus group B associated with problems of the perinatal period. Am. J. Obstet. Gynecol. 82:809–818.
    36.
    Eickhoff TC, Klein JO, Daly AK, Ingall D, and Finland M. 1964. Neonatal sepsis and other infections due to group B beta-hemolytic streptococci. N. Engl. J. Med. 271:1221–1228.
    37.
    Puopolo KM and Eichenwald EC. 2010. No change in the incidence of ampicillin-resistant, neonatal, early-onset sepsis over 18 years. Pediatrics 125:e1031–e1038.
    38.
    Nealon TJ and Mattingly SJ. 1983. Association of elevated levels of cellular lipoteichoic acids of group B streptococci with human neonatal disease. Infect. Immun. 39:1243–1251.
    39.
    Phares CR, Lynfield R, Farley MM, Mohle-Boetani J, Harrison LH, Petit S, Craig AS, Schaffner W, Zansky SM, Gershman K, Stefonek KR, Albanese BA, Zell ER, Schuchat A, Schrag SJ, and Active Bacterial Core Surveillance/Emerging Infections Program Network. 2008. Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005. JAMA 299:2056–2065.
    40.
    Klinger G, Levy I, Sirota L, Boyko V, Reichman B, Lerner-Geva L, and Israel Neonatal Network. 2009. Epidemiology and risk factors for early onset sepsis among very-low-birthweight infants. Am. J. Obstet. Gynecol. 201:38.e1–38.e6.
    41.
    Verboon-Maciolek MA, Krediet TG, Gerards LJ, Fleer A, and van Loon TM. 2005. Clinical and epidemiologic characteristics of viral infections in a neonatal intensive care unit during a 12-year period. Pediatr. Infect. Dis. J. 24:901–904.
    42.
    Pinninti SG, Angara R, Feja KN, Kimberlin DW, Leach CT, Conrad DA, McCarthy CA, and Tolan RW Jr. 2012. Neonatal herpes disease following maternal antenatal antiviral suppressive therapy: a multicenter case series. J. Pediatr. 161:134–138.e3.
    43.
    Baldwin S and Whitley RJ. 1989. Intrauterine herpes simplex virus infection. Teratology 39:1–10.
    44.
    Monif GR, Kellner KR, and Donnelly WH Jr. 1985. Congenital herpes simplex type II infection. Am. J. Obstet. Gynecol. 152:1000–1002.
    45.
    Hutto C, Arvin A, Jacobs R, Steele R, Stagno S, Lyrene R, Willett L, Powell D, Andersen R, and Werthammer J. 1987. Intrauterine herpes simplex virus infections. J. Pediatr. 110:97–101.
    46.
    Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Corey L, Gruber WC, Rathore M, Bradley JS, Diaz PS, Kumar M, Arvin AM, Gutierrez K, Shelton M, Weiner LB, Sleasman JW, de Sierra TM, Weller S, Soong SJ, Kiell J, Lakeman FD, Whitley RJ, and National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. 2001. Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections. Pediatrics 108:230–238.
    47.
    Whitley R, Arvin A, Prober C, Burchett S, Corey L, Powell D, Plotkin S, Starr S, Alford C, and Connor J. 1991. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group. N. Engl. J. Med. 324:444–449.
    48.
    Stanway G and Hyypia T. 1999. Parechoviruses. J. Virol. 73:5249–5254.
    49.
    Johnson I, Hammond GW, and Verma MR. 1985. Nosocomial coxsackie B4 virus infections in two chronic-care pediatric neurological wards. J. Infect. Dis. 151:1153–1156.
    50.
    Tebruegge M and Curtis N. 2009. Enterovirus infections in neonates. Semin. Fetal. Neonatal Med. 14:222–227.
    51.
    Lopez Sastre JB, Coto Cotallo GD, Fernandez Colomer B, and Grupo de Hospitales Castrillo. 2003. Neonatal invasive candidiasis: a prospective multicenter study of 118 cases. Am. J. Perinatol. 20:153–163.
    52.
    Benjamin DK Jr, Stoll BJ, Fanaroff AA, McDonald SA, Oh W, Higgins RD, Duara S, Poole K, Laptook A, Goldberg R, and National Institute of Child Health and Human Development Neonatal Research Network. 2006. Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics 117:84–92.
    53.
    Nizet V, Ferrieri P, and Rubens CE. 2000. Molecular pathogenesis of group B streptococcal disease in newborns, p 180–221. In Stevens DL and Kaplan EL (ed), Streptococcal infections: clinical aspects, microbiology and molecular pathogenesis. Oxford University Press, New York, NY.
    54.
    Campbell JR, Hillier SL, Krohn MA, Ferrieri P, Zaleznik DF, and Baker CJ. 2000. Group B streptococcal colonization and serotype-specific immunity in pregnant women at delivery. Obstet. Gynecol. 96:498–503.
    55.
    Schuchat A, Oxtoby M, Cochi S, Sikes RK, Hightower A, Plikaytis B, and Broome CV. 1990. Population-based risk factors for neonatal group B streptococcal disease: results of a cohort study in metropolitan Atlanta. J. Infect. Dis. 162:672–677.
    56.
    Bizzarro MJ, Dembry LM, Baltimore RS, and Gallagher PG. 2008. Changing patterns in neonatal Escherichia coli sepsis and ampicillin resistance in the era of intrapartum antibiotic prophylaxis. Pediatrics 121:689–696.
    57.
    Shane AL and Stoll BJ. 2013. Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis. Am. J. Perinatol. 30:131–142.
    58.
    Xie Y, Kim KJ, and Kim KS. 2004. Current concepts on Escherichia coli K1 translocation of the blood-brain barrier. FEMS Immunol. Med. Microbiol. 42:271–279.
    59.
    McCracken G and Sarff L. 1974. Current status and therapy of neonatal E. coli meningitis. Hosp. Pract. 9:57–64.
    60.
    Huang SH, Stins MF, and Kim KS. 2000. Bacterial penetration across the blood-brain barrier during the development of neonatal meningitis. Microbes Infect. 2:1237–1244.
    61.
    Gellin BG, Broome CV, Bibb WF, Weaver RE, Gaventa S, and Mascola L. 1991. The epidemiology of listeriosis in the United States—1986. Listeriosis Study Group. Am. J. Epidemiol. 133:392–401.
    62.
    Goulet V, Hedberg C, Le Monnier A, and de Valk H. 2008. Increasing incidence of listeriosis in France and other European countries. Emerg. Infect. Dis. 14:734–740.
    63.
    Niels le Souef P and Walters BN. 1981. Neonatal listeriosis: a summer outbreak. Med. J. Aust. 2:188–191.
    64.
    Wilson CB and Lewis DB. 1990. Basis and implications of selectively diminished cytokine production in neonatal susceptibility to infection. Rev. Infect. Dis. 12:S410–S420.
    65.
    Hunter CJ and Bean JF. 2013. Cronobacter: an emerging opportunistic pathogen associated with neonatal meningitis, sepsis and necrotizing enterocolitis. J. Perinatol. 33:581–585.
    66.
    Andre P, Thebaud B, Guibert M, Audibert F, Lacaze-Masmonteil T, and Dehan M. 2000. Maternal-fetal staphylococcal infections: a series report. Am. J. Perinatol. 17:423–427.
    67.
    D'Angio CT, McGowan KL, Baumgart S, St Geme J, and Harris MC. 1989. Surface colonization with coagulase-negative staphylococci in premature neonates. J. Pediatr. 114:1029–1034.
    68.
    Stoll BJ and Hansen N. 2003. Infections in VLBW infants: studies from the NICHD Neonatal Research Network. Semin. Perinatol. 27:293–301.
    69.
    Roque H, Abdelhak Y, and Young BK. 1999. Intra amniotic candidiasis. Case report and meta-analysis of 54 cases. J. Perinat. Med. 27:253–262.
    70.
    Darmstadt GL, Dinulos JG, and Miller Z. 2000. Congenital cutaneous candidiasis: clinical presentation, pathogenesis, and management guidelines. Pediatrics 105:438–444.
    71.
    Kaufman D and Fairchild KD. 2004. Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants. Clin. Microbiol. Rev. 17:638–680.
    72.
    Morris SR, Bauer HM, Samuel MC, Gallagher D, and Bolan G. 2008. Neonatal herpes morbidity and mortality in California, 1995-2003. Sex. Transm. Dis. 35:14–18.
    73.
    Gutierrez KM, Falkovitz Halpern MS, Maldonado Y, and Arvin AM. 1999. The epidemiology of neonatal herpes simplex virus infections in California from 1985 to 1995. J. Infect. Dis. 180:199–202.
    74.
    Whitley R, Davis EA, and Suppapanya N. 2007. Incidence of neonatal herpes simplex virus infections in a managed-care population. Sex. Transm. Dis. 34:704–708.
    75.
    Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, and Corey L. 2003. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA 289:203–209.
    76.
    Corey L and Wald A. 2009. Maternal and neonatal herpes simplex virus infections. N. Engl. J. Med. 361:1376–1385.
    77.
    Pinninti SG and Kimberlin DW. 2013. Neonatal herpes simplex virus infections. Pediatr. Clin. North Am. 60:351–365.
    78.
    Toth C, Harder S, and Yager J. 2003. Neonatal herpes encephalitis: a case series and review of clinical presentation. Can. J. Neurol. Sci. 30:36–40. http://cjns.metapress.com/content/efkmww7erj3qth1y/fulltext.pdf.
    79.
    Mizrahi EM and Tharp BR. 1982. A characteristic EEG pattern in neonatal herpes simplex encephalitis. Neurology 32:1215–1220.
    80.
    Vossough A, Zimmerman RA, Bilaniuk LT, and Schwartz EM. 2008. Imaging findings of neonatal herpes simplex virus type 2 encephalitis. Neuroradiology 50:355–366.
    81.
    Hyypia T, Horsnell C, Maaronen M, Khan M, Kalkkinen N, Auvinen P, Kinnunen L, and Stanway G. 1992. A distinct picornavirus group identified by sequence analysis. Proc. Natl. Acad. Sci. U. S. A. 89:8847–8851.
    82.
    Jenista JA, Powell KR, and Menegus MA. 1984. Epidemiology of neonatal enterovirus infection. J. Pediatr. 104:685–690.
    83.
    Rosenlew M, Stenvik M, Roivainen M, Jarvenpaa AL, and Hovi T. 1999. A population-based prospective survey of newborn infants with suspected systemic infection: occurrence of sporadic enterovirus and adenovirus infections. J. Clin. Virol. 12:211–219.
    84.
    Selvarangan R, Nzabi M, Selvaraju SB, Ketter P, Carpenter C, and Harrison CJ. 2011. Human parechovirus 3 causing sepsis-like illness in children from midwestern United States. Pediatr. Infect. Dis. J. 30:238–242.
    85.
    Abzug MJ, Levin MJ, and Rotbart HA. 1993. Profile of enterovirus disease in the first two weeks of life. Pediatr. Infect. Dis. J. 12:820–824.
    86.
    Lake AM, Lauer BA, Clark JC, Wesenberg RL, and McIntosh K. 1976. Enterovirus infections in neonates. J. Pediatr. 89:787–791.
    87.
    Modlin JF, Polk BF, Horton P, Etkind P, Crane E, and Spiliotes A. 1981. Perinatal echovirus infection: risk of transmission during a community outbreak. N. Engl. J. Med. 305:368–371.
    88.
    Haddad J, Gut JP, Wendling MJ, Astruc D, Jernite M, Obert G, and Messer J. 1993. Enterovirus infections in neonates. A retrospective study of 21 cases. Eur. J. Med. 2:209–214.
    89.
    Jones MJ, Kolb M, Votava HJ, Johnson RL, and Smith TF. 1980. Intrauterine echovirus type II infection. Mayo Clin. Proc. 55:509–512.
    90.
    Kaplan MH, Klein SW, McPhee J, and Harper RG. 1983. Group B coxsackievirus infections in infants younger than three months of age: a serious childhood illness. Rev. Infect. Dis. 5:1019–1032.
    91.
    Modlin JF. 1986. Perinatal echovirus infection: insights from a literature review of 61 cases of serious infection and 16 outbreaks in nurseries. Rev. Infect. Dis. 8:918–926.
    92.
    Brightman VJ, Scott TF, Westphal M, and Boggs TR. 1966. An outbreak of coxsackie B-5 virus infection in a newborn nursery. J. Pediatr. 69:179–192.
    93.
    Boyd MT, Jordan SW, and Davis LE. 1987. Fatal pneumonitis from congenital echovirus type 6 infection. Pediatr. Infect. Dis. J. 6:1138–1139.
    94.
    Burch GE, Sun SC, Chu KC, Sohal RS, and Colcolough HL. 1968. Interstitial and coxsackievirus B myocarditis in infants and children. A comparative histologic and immunofluorescent study of 50 autopsied hearts. JAMA 203:1–8.
    95.
    Strong BS and Young SA. 1995. Intrauterine coxsackie virus, group B type 1, infection: viral cultivation from amniotic fluid in the third trimester. Am. J. Perinatol. 12:78–79.
    96.
    Philip AG and Larson EJ. 1973. Overwhelming neonatal infection with ECHO 19 virus. J. Pediatr. 82:391–397.
    97.
    Berkovich S and Smithwick EM. 1968. Transplacental infection due to ECHO virus type 22. J. Pediatr. 72:94–96.
    98.
    Verboon-Maciolek MA, Groenendaal F, Hahn CD, Hellmann J, van Loon AM, Boivin G, and de Vries LS. 2008. Human parechovirus causes encephalitis with white matter injury in neonates. Ann. Neurol. 64:266–273.
    99.
    Wolthers KC, Benschop KS, Schinkel J, Molenkamp R, Bergevoet RM, Spijkerman IJ, Kraakman HC, and Pajkrt D. 2008. Human parechoviruses as an important viral cause of sepsislike illness and meningitis in young children. Clin. Infect. Dis. 47:358–363.
    100.
    Nizet V and Klein JO. 2011. Enterovirus and parechovirus infections, p 756–799. In Remigton JS, Klein JO, Wilson CB, Nizet V, and Maldonado YA (ed), Infectious diseases of the fetus and newborn, 7th ed. Elsevier Saunders, Philadelphia, PA.
    101.
    Lim WH, Lien R, Huang YC, Chiang MC, Fu RH, Chu SM, Hsu JF, and Yang PH. 2012. Prevalence and pathogen distribution of neonatal sepsis among very-low-birth-weight infants. Pediatr. Neonatol. 53:228–234.
    102.
    Verani JR, McGee L, Schrag SJ, and Division of Bacterial Diseases National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. 2010. Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, 2010. MMWR Recommend. Rep. 59(RR-10):1–36. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htm.
    103.
    Baker CJ, Edwards MS, and Kasper DL. 1981. Role of antibody to native type III polysaccharide of group B Streptococcus in infant infection. Pediatrics 68:544–549.
    104.
    Boyer KM, Gadzala CA, Burd LI, Fisher DE, Paton JB, and Gotoff SP. 1983. Selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease. I. Epidemiologic rationale. J. Infect. Dis. 148:795–801.
    105.
    Zaleznik DF, Rench MA, Hillier S, Krohn MA, Platt R, Lee ML, Flores AE, Ferrieri P, and Baker CJ. 2000. Invasive disease due to group B Streptococcus in pregnant women and neonates from diverse population groups. Clin. Infect. Dis. 30:276–281.
    106.
    Oddie S and Embleton ND. 2002. Risk factors for early onset neonatal group B streptococcal sepsis: case-control study. BMJ 325:308.
    107.
    Schuchat A, Zywicki SS, Dinsmoor MJ, Mercer B, Romaguera J, O'Sullivan MJ, Patel D, Peters MT, Stoll B, and Levine OS. 2000. Risk factors and opportunities for prevention of early-onset neonatal sepsis: a multicenter case-control study. Pediatrics 105:21–26.
    108.
    Verboon-Maciolek MA, Krediet TG, Gerards LJ, de Vries LS, Groenendaal F, and van Loon AM. 2008. Severe neonatal parechovirus infection and similarity with enterovirus infection. Pediatr. Infect. Dis. J. 27:241–245.
    109.
    Verboon-Maciolek MA, Groenendaal F, Cowan F, Govaert P, van Loon AM, and de Vries LS. 2006. White matter damage in neonatal enterovirus meningoencephalitis. Neurology 66:1267–1269.
    110.
    Eyssette-Guerreau S, Boize P, Thibault M, and Sarda H. 2013. Neonatal parechovirus infection, fever, irritability and myositis. Arch. Pediatr. 20:772–774.
    111.
    Johnson CE, Whitwell JK, Pethe K, Saxena K, and Super DM. 1997. Term newborns who are at risk for sepsis: are lumbar punctures necessary? Pediatrics 99:E10.
    112.
    Manroe BL, Weinberg AG, Rosenfeld CR, and Browne R. 1979. The neonatal blood count in health and disease. I. Reference values for neutrophilic cells. J. Pediatr. 95:89–98.
    113.
    Christensen RD, Henry E, Jopling J, and Wiedmeier SE. 2009. The CBC: reference ranges for neonates. Semin. Perinatol. 33:3–11.
    114.
    Christensen RD, Rothstein G, Hill HR, and Hall RT. 1985. Fatal early onset group B streptococcal sepsis with normal leukocyte counts. Pediatr. Infect. Dis. 4:242–245.
    115.
    Engle WD and Rosenfeld CR. 1984. Neutropenia in high-risk neonates. J. Pediatr. 105:982–986.
    116.
    Schmutz N, Henry E, Jopling J, and Christensen RD. 2008. Expected ranges for blood neutrophil concentrations of neonates: the Manroe and Mouzinho charts revisited. J. Perinatol. 28:275–281.
    117.
    Christensen RD and Rothstein G. 1979. Pitfalls in the interpretation of leukocyte counts of newborn infants. Am. J. Clin. Pathol. 72:608–611.
    118.
    Lambert RM, Baer VL, Wiedmeier SE, Henry E, Burnett J, and Christensen RD. 2009. Isolated elevated blood neutrophil concentration at altitude does not require NICU admission if appropriate reference ranges are used. J. Perinatol. 29:822–825.
    119.
    Manzoni P, Mostert M, Galletto P, Gastaldo L, Gallo E, Agriesti G, and Farina D. 2009. Is thrombocytopenia suggestive of organism-specific response in neonatal sepsis? Pediatr. Int. 51:206–210.
    120.
    Murphy K and Weiner J. 2012. Use of leukocyte counts in evaluation of early-onset neonatal sepsis. Pediatr. Infect. Dis. J. 31:16–19.
    121.
    Guida JD, Kunig AM, Leef KH, McKenzie SE, and Paul DA. 2003. Platelet count and sepsis in very low birth weight neonates: is there an organism-specific response? Pediatrics 111:1411–1415.
    122.
    Schelonka RL, Chai MK, Yoder BA, Hensley D, Brockett RM, and Ascher DP. 1996. Volume of blood required to detect common neonatal pathogens. J. Pediatr. 129:275–278.
    123.
    Dietzman DE, Fischer GW, and Schoenknecht FD. 1974. Neonatal Escherichia coli septicemia—bacterial counts in blood. J. Pediatr. 85:128–130.
    124.
    Kellogg JA, Ferrentino FL, Goodstein MH, Liss J, Shapiro SL, and Bankert DA. 1997. Frequency of low level bacteremia in infants from birth to two months of age. Pediatr. Infect. Dis. J. 16:381–385.
    125.
    Connell TG, Rele M, Cowley D, Buttery JP, and Curtis N. 2007. How reliable is a negative blood culture result? Volume of blood submitted for culture in routine practice in a children's hospital. Pediatrics 119:891–896.
    126.
    Pourcyrous M, Korones SB, Bada HS, Patterson T, and Baselski V. 1988. Indwelling umbilical arterial catheter: a preferred sampling site for blood culture. Pediatrics 81:821–825.
    127.
    Anagnostakis D, Kamba A, Petrochilou V, Arseni A, and Matsaniotis N. 1975. Risk of infection associated with umbilical vein catheterization. A prospective study in 75 newborn infants. J. Pediatr. 86:759–765.
    128.
    Polin JI, Knox I, Baumgart S, Campman E, Mennuti MT, and Polin RA. 1981. Use of umbilical cord blood culture for detection of neonatal bacteremia. Obstet. Gynecol. 57:233–237.
    129.
    Gabay C and Kushner I. 1999. Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med. 340:448–454.
    130.
    Philip AG. 1985. Response of C-reactive protein in neonatal group B streptococcal infection. Pediatr. Infect. Dis. 4:145–148.
    131.
    Meem M, Modak JK, Mortuza R, Morshed M, Islam MS, and Saha SK. 2011. Biomarkers for diagnosis of neonatal infections: a systematic analysis of their potential as a point-of-care diagnostics. J. Glob. Health 1:201–209. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484777/?report=classic.
    132.
    Peltola H and Jaakkola M. 1988. C-reactive protein in early detection of bacteremic versus viral infections in immunocompetent and compromised children. J. Pediatr. 113:641–646.
    133.
    Benitz WE, Han MY, Madan A, and Ramachandra P. 1998. Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics 102:E41.
    134.
    Altunhan H, Annagur A, Ors R, and Mehmetoglu I. 2011. Procalcitonin measurement at 24 hours of age may be helpful in the prompt diagnosis of early-onset neonatal sepsis. Int. J. Infect. Dis. 15:e854–e858.
    135.
    Monneret G, Labaune JM, Isaac C, Bienvenu F, Putet G, and Bienvenu J. 1997. Procalcitonin and C-reactive protein levels in neonatal infections. Acta Paediatr. 86:209–212.
    136.
    Maniaci V, Dauber A, Weiss S, Nylen E, Becker KL, and Bachur R. 2008. Procalcitonin in young febrile infants for the detection of serious bacterial infections. Pediatrics 122:701–710.
    137.
    Auriti C, Fiscarelli E, Ronchetti MP, Argentieri M, Marrocco G, Quondamcarlo A, Seganti G, Bagnoli F, Buonocore G, Serra G, Bacolla G, Mastropasqua S, Mari A, Corchia C, Prencipe G, Piersigilli F, Rava L, and Di Ciommo V. 2012. Procalcitonin in detecting neonatal nosocomial sepsis. Arch. Dis. Child. Fetal Neonatal Ed. 97:F368–F370.
    138.
    Kuster H, Weiss M, Willeitner AE, Detlefsen S, Jeremias I, Zbojan J, Geiger R, Lipowsky G, and Simbruner G. 1998. Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. Lancet 352:1271–1277.
    139.
    Chiesa C, Signore F, Assumma M, Buffone E, Tramontozzi P, Osborn JF, and Pacifico L. 2001. Serial measurements of C-reactive protein and interleukin-6 in the immediate postnatal period: reference intervals and analysis of maternal and perinatal confounders. Clin. Chem. 47:1016–1022. http://www.clinchem.org/content/47/6/1016.long.
    140.
    Celik İH, Demirel FG, Uras N, Oguz SS, Erdeve O, Biyikli Z, and Dilmen U. 2010. What are the cut-off levels for IL-6 and CRP in neonatal sepsis? J. Clin. Lab. Anal. 24:407–412.
    141.
    Abdollahi A, Shoar S, Nayyeri F, and Shariat M. 2012. Diagnostic value of simultaneous measurement of procalcitonin, interleukin-6 and hs-CRP in prediction of early-onset neonatal sepsis. Mediterr. J. Hematol. Infect. Dis. 4:e2012028.
    142.
    Venkatesh M, Flores A, Luna RA, and Versalovic J. 2010. Molecular microbiological methods in the diagnosis of neonatal sepsis. Expert Rev. Anti Infect. Ther. 8:1037–1048.
    143.
    Peters RPH, van Agtmael MA, Danner SA, Savelkoul PHM, and Vandenbroucke-Grauls CMJE. 2004. New developments in the diagnosis of bloodstream infections. Lancet Infect. Dis. 4:751–760.
    144.
    Weile J and Knabbe C. 2009. Current applications and future trends of molecular diagnostics in clinical bacteriology. Anal. Bioanal. Chem. 394:731–742.
    145.
    Lucignano B, Ranno S, Liesenfeld O, Pizzorno B, Putignani L, Bernaschi P, and Menichella D. 2011. Multiplex PCR allows rapid and accurate diagnosis of bloodstream infections in newborns and children with suspected sepsis. J. Clin. Microbiol. 49:2252–2258.
    146.
    Jordan JA and Durso MB. 2005. Real-time polymerase chain reaction for detecting bacterial DNA directly from blood of neonates being evaluated for sepsis. J. Mol. Diagn. 7:575–581.
    147.
    Jordan JA, Durso MB, Butchko AR, Jones JG, and Brozanski BS. 2006. Evaluating the near-term infant for early onset sepsis: progress and challenges to consider with 16S rDNA polymerase chain reaction testing. J. Mol. Diagn. 8:357–363.
    148.
    Reier-Nilsen T, Farstad T, Nakstad B, Lauvrak V, and Steinbakk M. 2009. Comparison of broad range 16S rDNA PCR and conventional blood culture for diagnosis of sepsis in the newborn: a case control study. BMC Pediatr. 9:5.
    149.
    Andrade SS, Bispo PJM, and Gales AC. 2008. Advances in the microbiological diagnosis of sepsis. Shock 30(Suppl 1):41–46.
    150.
    Jordan JA, Jones-Laughner J, and Durso MB. 2009. Utility of pyrosequencing in identifying bacteria directly from positive blood culture bottles. J. Clin. Microbiol. 47:368–372.
    151.
    Clarridge JE III. 2004. Impact of 16S rRNA gene sequence analysis for identification of bacteria on clinical microbiology and infectious diseases. Clin. Microbiol. Rev. 17:840–862.
    152.
    Ye RW, Wang T, Bedzyk L, and Croker KM. 2001. Applications of DNA microarrays in microbial systems. J. Microbiol. Methods 47:257–272.
    153.
    Shang S, Chen G, Wu Y, Du L, and Zhao Z. 2005. Rapid diagnosis of bacterial sepsis with PCR amplification and microarray hybridization in 16S rRNA gene. Pediatr. Res. 58:143–148.
    154.
    Cleven BE, Palka-Santini M, Gielen J, Meembor S, Kronke M, and Krut O. 2006. Identification and characterization of bacterial pathogens causing bloodstream infections by DNA microarray. J. Clin. Microbiol. 44:2389–2397.
    155.
    Visser VE and Hall RT. 1979. Urine culture in the evaluation of suspected neonatal sepsis. J. Pediatr. 94:635–638.
    156.
    Riskin A, Toropine A, Bader D, Hemo M, Srugo I, and Kugelman A. 2013. Is it justified to include urine cultures in early (< 72 hours) neonatal sepsis evaluations of term and late preterm infants? Am. J. Perinatol. 30:499–504.
    157.
    Tamim MM, Alesseh H, and Aziz H. 2003. Analysis of the efficacy of urine culture as part of sepsis evaluation in the premature infant. Pediatr. Infect. Dis. J. 22:805–808.
    158.
    Kramer MS, Tange SM, Drummond KN, and Mills EL. 1994. Urine testing in young febrile children: a risk-benefit analysis. J. Pediatr. 125:6–13.
    159.
    Bonadio WA. 1987. Urine culturing technique in febrile infants. Pediatr. Emerg. Care 3:75–78.
    160.
    Pryles CV, Atkin MD, Morse TS, and Welch KJ. 1959. Comparative bacteriologic study of urine obtained from children by percutaneous suprapubic aspiration of the bladder and by catheter. Pediatrics 24:983–991.
    161.
    Leong YY and Tan KW. 1976. Bladder aspiration for diagnosis of urinary tract infection in infants and young children. J. Singapore Paediatr. Soc. 18:43–47.
    162.
    Downs SM. 1999. Technical report: urinary tract infections in febrile infants and young children. The Urinary Tract Subcommittee of the American Academy of Pediatrics Committee on Quality Improvement. Pediatrics 103:e54. http://www.pediatricsdigest.mobi/content/103/4/e54.full.pdf+html.
    163.
    Shaw KN, McGowan KL, Gorelick MH, and Schwartz JS. 1998. Screening for urinary tract infection in infants in the emergency department: which test is best? Pediatrics 101:E1. http://www.pediatricsdigest.mobi/content/101/6/e1.full.pdf+html.
    164.
    Eldadah M, Frenkel LD, Hiatt IM, and Hegyi T. 1987. Evaluation of routine lumbar punctures in newborn infants with respiratory distress syndrome. Pediatr. Infect. Dis. J. 6:243–246.
    165.
    Isaacs D, Barfield CP, Grimwood K, McPhee AJ, Minutillo C, and Tudehope DI. 1995. Systemic bacterial and fungal infections in infants in Australian neonatal units. Australian Study Group for Neonatal Infections. Med. J. Aust. 162:198–201.
    166.
    Garges HP, Moody MA, Cotten CM, Smith PB, Tiffany KF, Lenfestey R, Li JS, Fowler VG, and Benjamin DK. 2006. Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters? Pediatrics 117:1094–1100.
    167.
    Prober CG and Dyner L. 2011. Central nervous system infections, p 2090–2095. In Kliegman RM, Stanton BF, Behrman RE, St Geme J, and Schor N (ed), Nelson textbook of pediatrics, 19th ed. Elsevier Saunders, Philadelphia, PA.
    168.
    Addy DP. 1987. When not to do a lumbar puncture. Arch. Dis. Child. 62:873–875.
    169.
    Mellor DH. 1992. The place of computed tomography and lumbar puncture in suspected bacterial meningitis. Arch. Dis. Child. 67:1417–1419.
    170.
    Pollard AJ, Britto J, Nadel S, DeMunter C, Habibi P, and Levin M. 1999. Emergency management of meningococcal disease. Arch. Dis. Child. 80:290–296.
    171.
    Kestenbaum LA, Ebberson J, Zorc JJ, Hodinka RL, and Shah SS. 2010. Defining cerebrospinal fluid white blood cell count reference values in neonates and young infants. Pediatrics 125:257–264.
    172.
    Martin-Ancel A, Garcia-Alix A, Salas S, Del Castillo F, Cabanas F, and Quero J. 2006. Cerebrospinal fluid leucocyte counts in healthy neonates. Arch. Dis. Child. Fetal Neonatal Ed. 91:F357–F358.
    173.
    Ahmed A, Hickey SM, Ehrett S, Trujillo M, Brito F, Goto C, Olsen K, Krisher K, and McCracken GH. 1996. Cerebrospinal fluid values in the term neonate. Pediatr. Infect. Dis. J. 15:298–303.
    174.
    Nascimento-Carvalho CM and Moreno-Carvalho OA. 1998. Normal cerebrospinal fluid values in full-term gestation and premature neonates. Arq. Neuropsiquiatr. 56:375–380.
    175.
    Shah SS, Aronson PL, Mohamad Z, and Lorch SA. 2011. Delayed acyclovir therapy and death among neonates with herpes simplex virus infection. Pediatrics 128:1153–1160.
    176.
    Byington CL, Kendrick J, and Sheng X. 2011. Normative cerebrospinal fluid profiles in febrile infants. J. Pediatr. 158:130–134.
    177.
    Chadwick SL, Wilson JW, Levin JE, and Martin JM. 2011. Cerebrospinal fluid characteristics of infants who present to the emergency department with fever: establishing normal values by week of age. Pediatr. Infect. Dis. J. 30:e63–e67.
    178.
    Smith PB, Garges HP, Cotton CM, Walsh TJ, Clark RH, and Benjamin DK Jr. 2008. Meningitis in preterm neonates: importance of cerebrospinal fluid parameters. Am. J. Perinatol. 25:421–426.
    179.
    Smith PB, Cotten CM, Garges HP, Tiffany KF, Lenfestey RW, Moody MA, Li JS, and Benjamin DK. 2006. A comparison of neonatal Gram-negative rod and Gram-positive cocci meningitis. J. Perinatol. 26:111–114.
    180.
    Bonadio WA, Smith DS, Goddard S, Burroughs J, and Khaja G. 1990. Distinguishing cerebrospinal fluid abnormalities in children with bacterial meningitis and traumatic lumbar puncture. J. Infect. Dis. 162:251–254.
    181.
    Mazor SS, McNulty JE, and Roosevelt GE. 2003. Interpretation of traumatic lumbar punctures: who can go home? Pediatrics 111:525–528. http://pediatrics.aappublications.org/content/111/3/525.long.
    182.
    Greenberg RG, Smith PB, Cotten CM, Moody MA, Clark RH, and Benjamin DK. 2008. Traumatic lumbar punctures in neonates: test performance of the cerebrospinal fluid white blood cell count. Pediatr. Infect. Dis. J. 27:1047–1051.
    183.
    Krajden S and Middleton PJ. 1983. Enterovirus infections in the neonate. Clin. Pediatr. (Phila.) 22:87–92.
    184.
    Rajesh NT, Dutta S, Prasad R, and Narang A. 2010. Effect of delay in analysis on neonatal cerebrospinal fluid parameters. Arch. Dis. Child. Fetal Neonatal Ed. 95:F25–F29.
    185.
    Shah SS, Ebberson J, Kestenbaum LA, Hodinka RL, and Zorc JJ. 2011. Age-specific reference values for cerebrospinal fluid protein concentration in neonates and young infants. J. Hosp. Med. 6:22–27.
    186.
    Wolf H and Hoepffner L. 1961. The cerebrospinal fluid in the newborn and premature infant. World Neurol. 2:871–878.
    187.
    Gyllensward A and Malmstrom S. 1962. The cerebrospinal fluid in immature infants. Acta Paediatr. Suppl. 135:54–62.
    188.
    Sarff LD, Platt LH, and McCracken GH Jr. 1976. Cerebrospinal fluid evaluation in neonates: comparison of high-risk infants with and without meningitis. J. Pediatr. 88:473–477.
    189.
    Rodriguez AF, Kaplan SL, and Mason EO Jr. 1990. Cerebrospinal fluid values in the very low birth weight infant. J. Pediatr. 116:971–974.
    190.
    Nijhuis M, van Maarseveen N, Schuurman R, Verkuijlen S, de Vos M, Hendriksen K, and van Loon AM. 2002. Rapid and sensitive routine detection of all members of the genus Enterovirus in different clinical specimens by real-time PCR. J. Clin. Microbiol. 40:3666–3670.
    191.
    Benschop K, Molenkamp R, van der Ham A, Wolthers K, and Beld M. 2008. Rapid detection of human parechoviruses in clinical samples by real-time PCR. J. Clin. Virol. 41:69–74.
    192.
    Nix WA, Maher K, Johansson ES, Niklasson B, Lindberg AM, Pallansch MA, and Oberste MS. 2008. Detection of all known parechoviruses by real-time PCR. J. Clin. Microbiol. 46:2519–2524.
    193.
    Beld M, Minnaar R, Weel J, Sol C, Damen M, van der Avoort H, Wertheim-van Dillen P, van Breda A, and Boom R. 2004. Highly sensitive assay for detection of enterovirus in clinical specimens by reverse transcription-PCR with an armored RNA internal control. J. Clin. Microbiol. 42:3059–3064.
    194.
    Whitley RJ. 1996. Herpes simplex viruses, p 2297–2342. In Fields BN, Knipe DM, and Howley PM (ed), Fields virology, 3rd ed. Lippincott-Raven Publishers, Philadelphia, PA.
    195.
    Whitley RJ, Corey L, Arvin A, Lakeman FD, Sumaya CV, Wright PF, Dunkle LM, Steele RW, Soong SJ, and Nahmias AJ. 1988. Changing presentation of herpes simplex virus infection in neonates. J. Infect. Dis. 158:109–116.
    196.
    Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Frenkel LM, Gruber WC, Rathore M, Bradley JS, Diaz PS, Kumar M, Arvin AM, Gutierrez K, Shelton M, Weiner LB, Sleasman JW, de Sierra TM, Soong SJ, Kiell J, Lakeman FD, Whitley RJ, and National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. 2001. Natural history of neonatal herpes simplex virus infections in the acyclovir era. Pediatrics 108:223–229.
    197.
    Whitley RJ, Yeager A, Kartus P, Bryson Y, Connor JD, Alford CA, Nahmias A, and Soong SJ. 1983. Neonatal herpes simplex virus infection: follow-up evaluation of vidarabine therapy. Pediatrics 72:778–785.
    198.
    American Academy of Pediatrics. 2012. Herpes simplex, p 398–408. In Pickering LK, Baker CJ, Kimberlin DW, and Long SS (ed), Red book: 2012 report of the Committee on Infectious Diseases. American Academy of Pediatrics, Elk Grove Village, IL.
    199.
    Kimberlin DW, Lakeman FD, Arvin AM, Prober CG, Corey L, Powell DA, Burchett SK, Jacobs RF, Starr SE, and Whitley RJ. 1996. Application of the polymerase chain reaction to the diagnosis and management of neonatal herpes simplex virus disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J. Infect. Dis. 174:1162–1167.
    200.
    Kimura H, Futamura M, Kito H, Ando T, Goto M, Kuzushima K, Shibata M, and Morishima T. 1991. Detection of viral DNA in neonatal herpes simplex virus infections: frequent and prolonged presence in serum and cerebrospinal fluid. J. Infect. Dis. 164:289–293.
    201.
    Kimberlin DW. 2007. Herpes simplex virus infections of the newborn. Semin. Perinatol. 31:19–25.
    202.
    Malm G and Forsgren M. 1999. Neonatal herpes simplex virus infections: HSV DNA in cerebrospinal fluid and serum. Arch. Dis. Child. Fetal Neonatal Ed. 81:F24–F29.
    203.
    Diamond C, Mohan K, Hobson A, Frenkel L, and Corey L. 1999. Viremia in neonatal herpes simplex virus infections. Pediatr. Infect. Dis. J. 18:487–489.
    204.
    Lim KA and Benyesh-Melnick M. 1960. Typing of viruses by combinations of antiserum pools. Application to typing of enteroviruses (Coxsackie and ECHO). J. Immunol. 84:309–317.
    205.
    Benschop KS, Schinkel J, Luken ME, van den Broek PJ, Beersma MF, Menelik N, van Eijk HW, Zaaijer HL, VandenBroucke-Grauls CM, Beld MG, and Wolthers KC. 2006. Fourth human parechovirus serotype. Emerg. Infect. Dis. 12:1572–1575.
    206.
    Abed Y and Boivin G. 2006. Human parechovirus types 1, 2 and 3 infections in Canada. Emerg. Infect. Dis. 12:969–975.
    207.
    Corless CE, Guiver M, Borrow R, Edwards-Jones V, Fox AJ, Kaczmarski EB, and Mutton KJ. 2002. Development and evaluation of a ‘real-time' RT-PCR for the detection of enterovirus and parechovirus RNA in CSF and throat swab samples. J. Med. Virol. 67:555–562.
    208.
    Baumgarte S, de Souza Luna LK, Grywna K, Panning M, Drexler JF, Karsten C, Huppertz HI, and Drosten C. 2008. Prevalence, types, and RNA concentrations of human parechoviruses, including a sixth parechovirus type, in stool samples from patients with acute enteritis. J. Clin. Microbiol. 46:242–248.
    209.
    Arola A, Santti J, Ruuskanen O, Halonen P, and Hyypia T. 1996. Identification of enteroviruses in clinical specimens by competitive PCR followed by genetic typing using sequence analysis. J. Clin. Microbiol. 34:313–318.
    210.
    Chapman NM, Tracy S, Gauntt CJ, and Fortmueller U. 1990. Molecular detection and identification of enteroviruses using enzymatic amplification and nucleic acid hybridization. J. Clin. Microbiol. 28:843–850.
    211.
    Selvaraju SB, Nix WA, Oberste MS, and Selvarangan R. 2013. Optimization of a combined human parechovirus-enterovirus real-time reverse transcription-PCR assay and evaluation of a new parechovirus 3-specific assay for cerebrospinal fluid specimen testing. J. Clin. Microbiol. 51:452–458.
    212.
    Kost CB, Rogers B, Oberste MS, Robinson C, Eaves BL, Leos K, Danielson S, Satya M, Weir F, and Nolte FS. 2007. Multicenter beta trial of the GeneXpert enterovirus assay. J. Clin. Microbiol. 45:1081–1086.
    213.
    McManus MC. 1997. Mechanisms of bacterial resistance to antimicrobial agents. Am. J. Health Syst. Pharm. 54:1420–1433, quiz 1444-1446.
    214.
    Jacqz-Aigrain E, Zhao W, Sharland M, and van den Anker JN. 2013. Use of antibacterial agents in the neonate: 50 years of experience with vancomycin administration. Semin. Fetal Neonatal Med. 18:28–34.
    215.
    Walker LA, Gow NA, and Munro CA. 2010. Fungal echinocandin resistance. Fungal Genet. Biol. 47:117–126.
    216.
    Chandel DS, Johnson JA, Chaudhry R, Sharma N, Shinkre N, Parida S, Misra PR, and Panigrahi P. 2011. Extended-spectrum beta-lactamase-producing Gram-negative bacteria causing neonatal sepsis in India in rural and urban settings. J. Med. Microbiol. 60:500–507.
    217.
    Dubois V, De Barbeyrac B, Rogues AM, Arpin C, Coulange L, Andre C, M'zali F, Megraud F, and Quentin C. 2010. CTX-M-producing Escherichia coli in a maternity ward: a likely community importation and evidence of mother-to-neonate transmission. J. Antimicrob. Chemother. 65:1368–1371.
    218.
    Bradford PA. 2001. Extended-spectrum β-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin. Microbiol. Rev. 14:933–951.
    219.
    Pitout JD and Laupland KB. 2008. Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect. Dis. 8:159–166.
    220.
    Ballot DE, Nana T, Sriruttan C, and Cooper PA. 2012. Bacterial bloodstream infections in neonates in a developing country. ISRN Pediatr. 2012:508512.
    221.
    Hsueh PR, Badal RE, Hawser SP, Hoban DJ, Bouchillon SK, Ni Y, Paterson DL, and 2008 Asia-Pacific SMART Group. 2010. Epidemiology and antimicrobial susceptibility profiles of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia-Pacific region: 2008 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). Int. J. Antimicrob. Agents 36:408–414.
    222.
    Villegas MV, Kattan JN, Quinteros MG, and Casellas JM. 2008. Prevalence of extended-spectrum beta-lactamases in South America. Clin. Microbiol. Infect. 14(Suppl 1):154–158.
    223.
    Doi Y, Park YS, Rivera JI, Adams-Haduch JM, Hingwe A, Sordillo EM, Lewis JS II, Howard WJ, Johnson LE, Polsky B, Jorgensen JH, Richter SS, Shutt KA, and Paterson DL. 2013. Community-associated extended-spectrum beta-lactamase-producing Escherichia coli infection in the United States. Clin. Infect. Dis. 56:641–648.
    224.
    MacGowan A, Wootton M, Bowker K, Holt HA, and Reeves D. 1998. Ampicillin-aminoglycoside interaction studies using Listeria monocytogenes. J. Antimicrob. Chemother. 41:417–418.
    225.
    Fink S, Karp W, and Robertson A. 1987. Ceftriaxone effect on bilirubin-albumin binding. Pediatrics 80:873–875.
    226.
    Schaad UB, Wedgwood-Krucko J, and Tschaeppeler H. 1988. Reversible ceftriaxone-associated biliary pseudolithiasis in children. Lancet ii:1411–1413.
    227.
    Avci Z, Koktener A, Uras N, Catal F, Karadag A, Tekin O, Degirmencioglu H, and Baskin E. 2004. Nephrolithiasis associated with ceftriaxone therapy: a prospective study in 51 children. Arch. Dis. Child. 89:1069–1072.
    228.
    Dulac Y, Bouissou F, Azema C, Barthe P, Baunin C, and Normand-Gottis M. 1995. Anuria caused by urinary lithiasis induced by ceftriaxone in a 6-year-old child. Presse Med. 24:916.
    229.
    Prince JS and Senac MO Jr. 2003. Ceftriaxone-associated nephrolithiasis and biliary pseudolithiasis in a child. Pediatr. Radiol. 33:648–651.
    230.
    Bradley JS, Wassel RT, Lee L, and Nambiar S. 2009. Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events. Pediatrics 123:e609–e613.
    231.
    Cordero L, Sananes M, and Ayers LW. 1999. Bloodstream infections in a neonatal intensive-care unit: 12 years' experience with an antibiotic control program. Infect. Control Hosp. Epidemiol. 20:242–246.
    232.
    Nagano N, Nagano Y, Toyama M, Kimura K, Tamura T, Shibayama K, and Arakawa Y. 2012. Nosocomial spread of multidrug-resistant group B streptococci with reduced penicillin susceptibility belonging to clonal complex 1. J. Antimicrob. Chemother. 67:849–856.
    233.
    Dahesh S, Hensler ME, Van Sorge NM, Gertz RE Jr, Schrag S, Nizet V, and Beall BW. 2008. Point mutation in the group B streptococcal pbp2x gene conferring decreased susceptibility to beta-lactam antibiotics. Antimicrob. Agents Chemother. 52:2915–2918.
    234.
    American Academy of Pediatrics. 2012. Group B strep, p 680–685. In Pickering LK, Baker CJ, Kimberlin DW, and Long SS (ed), Red book: 2012 report of the Committee on Infectious Diseases. American Academy of Pediatrics, Elk Grove Village, IL.
    235.
    Edwards MS and Baker CJ. 2012. Streptococcus agalactiae (group B streptococcus), p 707–712. In Long SS, Pickering LK, and Prober CG (ed), Principles and practice of pediatric infectious diseases, 4th ed. Elsevier, Edinburgh, United Kingdom.
    236.
    Edwards MS and Baker CJ. 2013. Treatment and outcome of bacterial meningitis in the neonate. In Basow DS (ed), UpToDate. UpToDate, Waltham, MA. http://www.uptodate.com/contents/treatment-and-outcome-of-bacterial-meningitis-in-the-neonate?source=preview&anchor=H9&selectedTitle=3∼150#H9. Accessed 11 November 2013.
    237.
    American Academy of Pediatrics. 2012. Escherichia coli and other gram-negative bacilli (septicemia and meningitis in neonates), p 321–324. In Pickering LK, Baker CJ, Kimberlin DW, and Long SS (ed), Red book: 2012 report of the Committee on Infectious Diseases. American Academy of Pediatrics, Elk Grove Village, IL.
    238.
    Arrieta A. 1997. Use of meropenem in the treatment of serious infections in children: review of the current literature. Clin. Infect. Dis. 24(Suppl 2):S207–S212.
    239.
    van den Anker JN, Pokorna P, Kinzig-Schippers M, Martinkova J, de Groot R, Drusano GL, and Sorgel F. 2009. Meropenem pharmacokinetics in the newborn. Antimicrob. Agents Chemother. 53:3871–3879.
    240.
    Messerschmidt A, Prayer D, Olischar M, Pollak A, and Birnbacher R. 2004. Brain abscesses after Serratia marcescens infection on a neonatal intensive care unit: differences on serial imaging. Neuroradiology 46:148–152.
    241.
    Kline MW and Kaplan SL. 1987. Citrobacter diversus and neonatal brain abscess. Pediatr. Neurol. 3:178–180.
    242.
    Bowen AB and Braden CR. 2006. Invasive Enterobacter sakazakii disease in infants. Emerg. Infect. Dis. 12:1185–1189.
    243.
    American Academy of Pediatrics. 2012. Listeria monocytogenes infection, p 471–474. In Pickering LK, Baker CJ, Kimberlin DW, and Long SS (ed), Red book: 2012 report of the Committee on Infectious Diseases. American Academy of Pediatrics, Elk Grove Village, IL.
    244.
    Schweizer ML, Furuno JP, Harris AD, Johnson JK, Shardell MD, McGregor JC, Thom KA, Cosgrove SE, Sakoulas G, and Perencevich EN. 2011. Comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia. BMC Infect. Dis. 11:279.
    245.
    Deville JG, Adler S, Azimi PH, Jantausch BA, Morfin MR, Beltran S, Edge-Padbury B, Naberhuis-Stehouwer S, and Bruss JB. 2003. Linezolid versus vancomycin in the treatment of known or suspected resistant gram-positive infections in neonates. Pediatr. Infect. Dis. J. 22:S158–S163.
    246.
    Yilmaz A, Dalgic N, Musluman M, Sancar M, Colak I, and Aydin Y. 2010. Linezolid treatment of shunt-related cerebrospinal fluid infections in children. J. Neurosurg. Pediatr. 5:443–448.
    247.
    Garazzino S and Tovo PA. 2011. Clinical experience with linezolid in infants and children. J. Antimicrob. Chemother. 66(Suppl 4):iv23–iv41.
    248.
    Yogev R, Damle B, Levy G, and Nachman S. 2010. Pharmacokinetics and distribution of linezolid in cerebrospinal fluid in children and adolescents. Pediatr. Infect. Dis. J. 29:827–830.
    249.
    Tripathi N, Watt K, and Benjamin DK Jr. 2012. Treatment and prophylaxis of invasive candidiasis. Semin. Perinatol. 36:416–423.
    250.
    Steinbach WJ, Roilides E, Berman D, Hoffman JA, Groll AH, Bin-Hussain I, Palazzi DL, Castagnola E, Halasa N, Velegraki A, Dvorak CC, Charkabarti A, Sung L, Danziger-Isakov L, Lachenauer C, Arrieta A, Knapp K, Abzug MJ, Ziebold C, Lehrnbecher T, Klingspor L, Warris A, Leckerman K, Martling T, Walsh TJ, Benjamin DK Jr, Zaoutis TE, and International Pediatric Fungal Network. 2012. Results from a prospective, international, epidemiologic study of invasive candidiasis in children and neonates. Pediatr. Infect. Dis. J. 31:1252–1257.
    251.
    Rex JH, Walsh TJ, Sobel JD, Filler SG, Pappas PG, Dismukes WE, and Edwards JE. 2000. Practice guidelines for the treatment of candidiasis. Infectious Diseases Society of America. Clin. Infect. Dis. 30:662–678.
    252.
    Anderson-Berry A, Brinton B, Lyden E, and Faix RG. 2011. Risk factors associated with development of persistent coagulase-negative staphylococci bacteremia in the neonate and associated short-term and discharge morbidities. Neonatology 99:23–31.
    253.
    Ascher SB, Smith PB, Watt K, Benjamin DK, Cohen-Wolkowiez M, Clark RH, Benjamin DK Jr, and Moran C. 2012. Antifungal therapy and outcomes in infants with invasive Candida infections. Pediatr. Infect. Dis. J. 31:439–443.
    254.
    Kimberlin DW, Whitley RJ, Wan W, Powell DA, Storch G, Ahmed A, Palmer A, Sanchez PJ, Jacobs RF, Bradley JS, Robinson JL, Shelton M, Dennehy PH, Leach C, Rathore M, Abughali N, Wright P, Frenkel LM, Brady RC, Van Dyke R, Weiner LB, Guzman-Cottrill J, McCarthy CA, Griffin J, Jester P, Parker M, Lakeman FD, Kuo H, Lee CH, Cloud GA, and National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. 2011. Oral acyclovir suppression and neurodevelopment after neonatal herpes. N. Engl. J. Med. 365:1284–1292.
    255.
    Touw DJ, Westerman EM, and Sprij AJ. 2009. Therapeutic drug monitoring of aminoglycosides in neonates. Clin. Pharmacokinet. 48:71–88.
    256.
    INIS Collaborative Group, Brocklehurst P, Farrell B, King A, Juszczak E, Darlow B, Haque K, Salt A, Stenson B, and Tarnow-Mordi W. 2011. Treatment of neonatal sepsis with intravenous immune globulin. N. Engl. J. Med. 365:1201–1211.
    257.
    Schibler KR, Osborne KA, Leung LY, Le TV, Baker SI, and Thompson DD. 1998. A randomized, placebo-controlled trial of granulocyte colony-stimulating factor administration to newborn infants with neutropenia and clinical signs of early-onset sepsis. Pediatrics 102:6–13.
    258.
    INIS Study Collaborative Group. 2008. The INIS Study. International Neonatal Immunotherapy Study. Non-specific intravenous immunoglobulin therapy for suspected or proven neonatal sepsis: an international, placebo controlled, multicentre randomised trial. BMC Pregnancy Childbirth 8:52.
    259.
    Gerdes JS. 2004. Diagnosis and management of bacterial infections in the neonate. Pediatr. Clin. North Am. 51:939–959, viii–ix.
    260.
    Edwards MS. 2013. Treatment and outcome of sepsis in term and late preterm infants. In Basow DS (ed), UpToDate. UpToDate, Waltham, MA. http://www.uptodate.com/contents/treatment-and-outcome-of-sepsis-in-term-and-late-preterm-infants?source=preview&anchor=H9&selectedTitle=1∼150#H9. Accessed 11 November 2013.
    261.
    Pourcyrous M, Bada HS, Korones SB, Baselski V, and Wong SP. 1993. Significance of serial C-reactive protein responses in neonatal infection and other disorders. Pediatrics 92:431–435.
    262.
    Weil AA, Glaser CA, Amad Z, and Forghani B. 2002. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clin. Infect. Dis. 34:1154–1157.
    263.
    Elbers JM, Bitnun A, Richardson SE, Ford-Jones EL, Tellier R, Wald RM, Petric M, Kolski H, Heurter H, and MacGregor D. 2007. A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease? Pediatrics 119:e399–e407.
    264.
    Paterson DL, Ko WC, Von Gottberg A, Casellas JM, Mulazimoglu L, Klugman KP, Bonomo RA, Rice LB, McCormack JG, and Yu VL. 2001. Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory. J. Clin. Microbiol. 39:2206–2212.
    265.
    Koenig JM and Keenan WJ. 2009. Group B streptococcus and early-onset sepsis in the era of maternal prophylaxis. Pediatr. Clin. North Am. 56:689–708.
    266.
    Lin CB, Hornik CP, Clark R, Cotten CM, Benjamin DK Jr, Cohen-Wolkoweiz M, Smith PB, and Wynn JL. 2012. Very low birth weight neonates who survive early-onset sepsis do not have an increased risk of developing late-onset sepsis. Early Hum. Dev. 88:905–909.
    267.
    Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, and Poole WK. 2002. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 110:285–291.
    268.
    Shah DK, Doyle LW, Anderson PJ, Bear M, Daley AJ, Hunt RW, and Inder TE. 2008. Adverse neurodevelopment in preterm infants with postnatal sepsis or necrotizing enterocolitis is mediated by white matter abnormalities on magnetic resonance imaging at term. J. Pediatr. 153:170–175.
    269.
    Taylor HG, Minich N, Bangert B, Filipek PA, and Hack M. 2004. Long-term neuropsychological outcomes of very low birth weight: associations with early risks for periventricular brain insults. J. Int. Neuropsychol. Soc. 10:987–1004.
    270.
    Pisani V, Bizzarri B, Cardi V, Pedicino R, Natale F, Stolfi I, Castronovo A, and De Curtis M. 2012. Early onset sepsis in very low birth weight newborn infants. J. Matern. Fetal Neonatal Med. 25(Suppl 3):21–25.
    271.
    Stoll BJ, Hansen NI, Higgins RD, Fanaroff AA, Duara S, Goldberg R, Laptook A, Walsh M, Oh W, Hale E, and National Institute of Child Health and Human Development. 2005. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003. Pediatr. Infect. Dis. J. 24:635–639.
    272.
    Whitley RJ, Nahmias AJ, Soong SJ, Galasso GG, Fleming CL, and Alford CA. 1980. Vidarabine therapy of neonatal herpes simplex virus infection. Pediatrics 66:495–501.
    273.
    Whitley R, Arvin A, Prober C, Corey L, Burchett S, Plotkin S, Starr S, Jacobs R, Powell D, and Nahmias A. 1991. Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. N. Engl. J. Med. 324:450–454.
    274.
    Isacsohn M, Eidelman AI, Kaplan M, Goren A, Rudensky B, Handsher R, and Barak Y. 1994. Neonatal coxsackievirus group B infections: experience of a single department of neonatology. Isr. J. Med. Sci. 30:371–374.
    275.
    Abzug MJ. 2001. Prognosis for neonates with enterovirus hepatitis and coagulopathy. Pediatr. Infect. Dis. J. 20:758–763.
    276.
    Centers for Disease Control and Prevention. 2008. Increased detections and severe neonatal disease associated with coxsackievirus B1 infection—United States, 2007. MMWR Morb. Mortal. Wkly. Rep. 57:553–556. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5720a4.htm.
    277.
    Leviton A, Dammann O, Engelke S, Allred E, Kuban KC, O'Shea TM, Paneth N, and ELGAN Study Investigators. 2010. The clustering of disorders in infants born before the 28th week of gestation. Acta Paediatr. 99:1795–1800.
    278.
    Jobe AH and Bancalari E. 2001. Bronchopulmonary dysplasia. Am. J. Respir. Crit. Care Med. 163:1723–1729.
    279.
    Watterberg KL, Demers LM, Scott SM, and Murphy S. 1996. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics 97:210–215.
    280.
    Kramer BW, Kramer S, Ikegami M, and Jobe AH. 2002. Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin. Am. J. Physiol. Lung Cell. Mol. Physiol. 283:L452–L459.
    281.
    Kallapur SG, Moss TJ, Ikegami M, Jasman RL, Newnham JP, and Jobe AH. 2005. Recruited inflammatory cells mediate endotoxin-induced lung maturation in preterm fetal lambs. Am. J. Respir. Crit. Care Med. 172:1315–1321.
    282.
    Adams-Chapman I. 2012. Long-term impact of infection on the preterm neonate. Semin. Perinatol. 36:462–470.
    283.
    Polin RA. 2008. Systemic infection and brain injury in the preterm infant. J. Pediatr. (Rio J.) 84:188–191.
    284.
    Klinger G, Levy I, Sirota L, Boyko V, Lerner-Geva L, Reichman B, and Israel Neonatal Network. 2010. Outcome of early-onset sepsis in a national cohort of very low birth weight infants. Pediatrics 125:e736–e740.
    285.
    Procianoy RS and Silveira RC. 2012. Association between high cytokine levels with white matter injury in preterm infants with sepsis. Pediatr. Crit. Care Med. 13:183–187.
    286.
    Rezaie P and Dean A. 2002. Periventricular leukomalacia, inflammation and white matter lesions within the developing nervous system. Neuropathology 22:106–132.
    287.
    Edwards M and Baker C. 2001. Group B streptococcal infections, p 1091–1156. In Remington J and Klein J. (ed), Infectious diseases of the fetus and the newborn infant, 5th ed. WB Saunders Co, Philadelphia, PA.
    288.
    Renna S, Bergamino L, Pirlo D, Rossi A, Furione M, Piralla A, Mascaretti M, Cristina E, Marazzi MG, and Pietro PD. 21 January 2013. A case of neonatal human parechovirus encephalitis with a favourable outcome. Brain Dev. [Epub ahead of print.] doi:
    289.
    Stafford IA, Stewart RD, Sheffield JS, Wendel GD Jr, Sanchez PJ, McIntire DD, and Roberts SW. 2012. Efficacy of maternal and neonatal chemoprophylaxis for early-onset group B streptococcal disease. Obstet. Gynecol. 120:123–129.
    290.
    Van Dyke MK, Phares CR, Lynfield R, Thomas AR, Arnold KE, Craig AS, Mohle-Boetani J, Gershman K, Schaffner W, Petit S, Zansky SM, Morin CA, Spina NL, Wymore K, Harrison LH, Shutt KA, Bareta J, Bulens SN, Zell ER, Schuchat A, and Schrag SJ. 2009. Evaluation of universal antenatal screening for group B streptococcus. N. Engl. J. Med. 360:2626–2636.
    291.
    Lin FY, Weisman LE, Azimi P, Young AE, Chang K, Cielo M, Moyer P, Troendle JF, Schneerson R, and Robbins JB. 2011. Assessment of intrapartum antibiotic prophylaxis for the prevention of early-onset group B streptococcal disease. Pediatr. Infect. Dis. J. 30:759–763.
    292.
    Davies HD, Miller MA, Faro S, Gregson D, Kehl SC, and Jordan JA. 2004. Multicenter study of a rapid molecular-based assay for the diagnosis of group B Streptococcus colonization in pregnant women. Clin. Infect. Dis. 39:1129–1135.
    293.
    Faro JP, Bishop K, Riddle G, Ramirez MM, Katz AR, Turrentine MA, and Faro S. 2013. Accuracy of an accelerated, culture-based assay for detection of group B streptococcus. Infect. Dis. Obstet. Gynecol. 2013:367935.
    294.
    Faro J, Katz A, Bishop K, Riddle G, and Faro S. 2011. Rapid diagnostic test for identifying group B streptococcus. Am. J. Perinatol. 28:811–814.
    295.
    Lin CY, Hsu CH, Huang FY, Chang JH, Hung HY, Kao HA, Peng CC, Jim WT, Chi H, Chiu NC, Chang TY, Chen CY, and Chen CP. 2011. The changing face of early-onset neonatal sepsis after the implementation of a maternal group B Streptococcus screening and intrapartum prophylaxis policy—a study in one medical center. Pediatr. Neonatol. 52:78–84.
    296.
    Simoes JA, Aroutcheva AA, Heimler I, and Faro S. 2004. Antibiotic resistance patterns of group B streptococcal clinical isolates. Infect. Dis. Obstet. Gynecol. 12:1–8.
    297.
    Pelaez LM, Gelber SE, Fox NS, and Chasen ST. 2009. Inappropriate use of vancomycin for preventing perinatal group B streptococcal (GBS) disease in laboring patients. J. Perinat. Med. 37:487–489.
    298.
    Committee on Infectious Diseases, Committee on Fetus and Newborn, Baker CJ, Byington CL, and Polin RA. 2011. Policy statement—recommendations for the prevention of perinatal group B streptococcal (GBS) disease. Pediatrics 128:611–616.
    299.
    Paccione KA and Wiesenfeld HC. 2013. Guideline adherence for intrapartum group B streptococci prophylaxis in penicillin-allergic patients. Infect. Dis. Obstet. Gynecol. 2013:917304.
    300.
    Manning SD, Foxman B, Pierson CL, Tallman P, Baker CJ, and Pearlman MD. 2003. Correlates of antibiotic-resistant group B streptococcus isolated from pregnant women. Obstet. Gynecol. 101:74–79.
    301.
    Ecker KL, Donohue PK, Kim KS, Shepard JA, and Aucott SW. 2013. The impact of group B streptococcus prophylaxis on late-onset neonatal infections. J. Perinatol. 33:206–211.
    302.
    Glasgow TS, Young PC, Wallin J, Kwok C, Stoddard G, Firth S, Samore M, and Byington CL. 2005. Association of intrapartum antibiotic exposure and late-onset serious bacterial infections in infants. Pediatrics 116:696–702.
    303.
    Baker CJ, Paoletti LC, Wessels MR, Guttormsen HK, Rench MA, Hickman ME, and Kasper DL. 1999. Safety and immunogenicity of capsular polysaccharide-tetanus toxoid conjugate vaccines for group B streptococcal types Ia and Ib. J. Infect. Dis. 179:142–150.
    304.
    Baker CJ and Kasper DL. 1985. Vaccination as a measure for prevention of neonatal GBS infection. Antibiot. Chemother. 35:281–290.
    305.
    Omer SB, Orenstein WA, and Koplan JP. 2013. Go big and go fast—vaccine refusal and disease eradication. N. Engl. J. Med. 368:1374–1376.
    306.
    Johri AK, Paoletti LC, Glaser P, Dua M, Sharma PK, Grandi G, and Rappuoli R. 2006. Group B Streptococcus: global incidence and vaccine development. Nat. Rev. Microbiol. 4:932–942.
    307.
    Donati C and Rappuoli R. 2013. Reverse vaccinology in the 21st century: improvements over the original design. Ann. N. Y. Acad. Sci. 1285:115–132.
    308.
    Baker CJ, Rench MA, Edwards MS, Carpenter RJ, Hays BM, and Kasper DL. 1988. Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus. N. Engl. J. Med. 319:1180–1185.
    309.
    Rodriguez-Granger J, Alvargonzalez JC, Berardi A, Berner R, Kunze M, Hufnagel M, Melin P, Decheva A, Orefici G, Poyart C, Telford J, Efstratiou A, Killian M, Krizova P, Baldassarri L, Spellerberg B, Puertas A, and Rosa-Fraile M. 2012. Prevention of group B streptococcal neonatal disease revisited. The DEVANI European project. Eur. J. Clin. Microbiol. Infect. Dis. 31:2097–2104.
    310.
    Eschenbach DA. 2002. Prevention of neonatal group B streptococcal infection. N. Engl. J. Med. 347:280–281.
    311.
    Baker CJ, Rench MA, Fernandez M, Paoletti LC, Kasper DL, and Edwards MS. 2003. Safety and immunogenicity of a bivalent group B streptococcal conjugate vaccine for serotypes II and III. J. Infect. Dis. 188:66–73.
    312.
    Baker CJ, Rench MA, Paoletti LC, and Edwards MS. 2007. Dose-response to type V group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine in healthy adults. Vaccine 25:55–63.
    313.
    Baker CJ, Paoletti LC, Rench MA, Guttormsen HK, Edwards MS, and Kasper DL. 2004. Immune response of healthy women to 2 different group B streptococcal type V capsular polysaccharide-protein conjugate vaccines. J. Infect. Dis. 189:1103–1112.
    314.
    Edwards MS, Lane HJ, Hillier SL, Rench MA, and Baker CJ. 2012. Persistence of functional antibodies to group B streptococcal capsular polysaccharides following immunization with glycoconjugate vaccines. Vaccine 30:4123–4126.
    315.
    Koumans EH, Rosen J, van Dyke MK, Zell E, Phares CR, Taylor A, Loft J, Schrag S, and ABC and DHAP/RTI Teams. 2012. Prevention of mother-to-child transmission of infections during pregnancy: implementation of recommended interventions, United States, 2003-2004. Am. J. Obstet. Gynecol. 206:158.e1–158.e11.
    316.
    Zaleznik DF, Rench MA, Hillier S, Krohn MA, Platt R, Lee M-LT, Flores AE, Ferrieri P, and Baker CJ. 2000. Invasive disease due to group B streptococcus in pregnant women and neonates from diverse population groups. Clin. Infect. Dis. 30:276–281.

    Author Bios

    Kari A. Simonsen
    Division of Infectious Diseases, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA
    Kari A. Simonsen is an Associate Professor and Division Chief of Pediatric Infectious Diseases at the University of Nebraska Medical Center (UNMC). Dr. Simonsen obtained her medical degree at the UNMC in 2001, followed by pediatric residency at Indiana University School of Medicine. Her fellowship training in Pediatric Infectious Diseases was at the Warren Alpert Medical School at Brown University, Providence, RI. She joined the faculty at UNMC in 2007 and has research interests in neonatal sepsis, including central venous catheter-associated infections and transfusion-associated babesiosis.
    Ann L. Anderson-Berry
    Division of Neonatology, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA
    Ann L. Anderson-Berry is an Associate Professor in the Division of Neonatology at the University of Nebraska Medical Center. She obtained her medical degree from Creighton University School of Medicine, Omaha, NE, in 1998. This was followed by a residency in Pediatrics at the Creighton University/University of Nebraska Pediatrics Program, also in Omaha, NE, in 2001. Her fellowship training in Neonatal-Perinatal Medicine was at the University of Utah School of Medicine, Salt Lake City, UT. Dr. Anderson-Berry joined the faculty of UNMC in 2004 and has been Medical Director of the NICU since 2010. Her major area of research interest related to sepsis is in catheter-associated infections in the VLBW infant.
    Shirley F. Delair
    Division of Infectious Diseases, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA
    Shirley F. Delair is an Assistant Professor in the Division of Pediatric Infectious Diseases at the University of Nebraska Medical Center (UNMC). Dr. Delair obtained her M.D. from the Institute of Health Sciences, CES University, Medellin, Colombia, in 2001. This was followed by Internship and Residency programs at the Saint Joseph Children's Hospital, Mount Sinai School of Medicine, Paterson, NJ, from 2004 to 2007. Dr. Delair's fellowship in infectious diseases was at the Mattel Children's Hospital, David Geffen School of Medicine at UCLA, Los Angeles, CA. She joined the faculty at UNMC in 2010 and has research interests in sepsis and infectious disease epidemiology.
    H. Dele Davies [email protected]
    Division of Infectious Diseases, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA
    H. Dele Davies is Professor of Pediatrics and Public Health at the University of Nebraska Medical Center. Dr. Davies received his M.D. from the University of Toronto in 1985, followed by pediatric residency and infectious diseases fellowships at the Hospital for Sick Children in Toronto, Canada (1992). Dr. Davies holds dual master's degrees in Epidemiology (Toronto) and in Health Care Management (Harvard School of Public Health). Dr. Davies has had a long-standing research area of interest in the clinical and molecular epidemiology of group B streptococcus-related infections. Prior to coming to the UNMC, Dr. Davies was on faculty at the University of Calgary for several years as Director of the Child Health Research Unit, followed by nine years as Professor and Chair of Pediatrics at Michigan State University. He has served or currently serves on U.S. and Canadian national advisory boards related to prevention and management of Infectious Diseases.

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    Clinical Microbiology Reviews
    Volume 27Number 1January 2014
    Pages: 21 - 47

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    Kari A. Simonsen
    Division of Infectious Diseases, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA
    Ann L. Anderson-Berry
    Division of Neonatology, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA
    Shirley F. Delair
    Division of Infectious Diseases, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA
    H. Dele Davies [email protected]
    Division of Infectious Diseases, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA

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  • Clinical Microbiology ReviewsArticle
    Human Melioidosis

    SUMMARY

    The causative agent of melioidosis, Burkholderia pseudomallei, a tier 1 select agent, is endemic in Southeast Asia and northern Australia, with increased incidence associated with high levels of rainfall. Increasing reports of this condition have occurred worldwide, with estimates of up to 165,000 cases and 89,000 deaths per year. The ecological niche of the organism has yet to be clearly defined, although the organism is associated with soil and water. The culture of appropriate clinical material remains the mainstay of laboratory diagnosis. Identification is best done by phenotypic methods, although mass spectrometric methods have been described. Serology has a limited diagnostic role. Direct molecular and antigen detection methods have limited availability and sensitivity. Clinical presentations of melioidosis range from acute bacteremic pneumonia to disseminated visceral abscesses and localized infections. Transmission is by direct inoculation, inhalation, or ingestion. Risk factors for melioidosis include male sex, diabetes mellitus, alcohol abuse, and immunosuppression. The organism is well adapted to intracellular survival, with numerous virulence mechanisms. Immunity likely requires innate and adaptive responses. The principles of management of this condition are drainage and debridement of infected material and appropriate antimicrobial therapy. Global mortality rates vary between 9% and 70%. Research into vaccine development is ongoing.

    REFERENCES

    1.
    Depoorter E, Bull MJ, Peeters C, Coenye T, Vandamme P, Mahenthiralingam E. 2016. Burkholderia: an update on taxonomy and biotechnological potential as antibiotic producers. Appl Microbiol Biotechnol 100:5215–5229.
    2.
    LiPuma JJ, Currie BJ, Peacock SJ, Vandamme PWE. 2015. Burkholderia, Stenotrophomonas, Ralstonia, Cupriavidus, Pandoraea, Brevundimonas, Comamonas, Delftia, and Acidovorax, p 791–812. In Jorgensen JH, Pfaller MA, Carroll KC, Funke G, Landry ML, Richter SS, Warnock DW (ed), Manual of clinical microbiology, 11th ed. ASM Press, Washington, DC.
    3.
    Peacock SJ, Schweizer HP, Dance DAB, Smith TL, Gee JE, Wuthiekanun V, DeShazer D, Steinmetz I, Tan P, Currie BJ. 2008. Management of accidental laboratory exposure to Burkholderia pseudomallei and B. mallei. Emerg Infect Dis 14:e2.
    4.
    Currie BJ, Jacups SP, Cheng AC, Fisher DA, Anstey NM, Huffam SE, Krause VL. 2004. Melioidosis epidemiology and risk factors from a prospective whole-population study in northern Australia. Trop Med Int Health 9:1167–1174.
    5.
    Vuddhakul V, Tharavichitkul P, Na-Ngam N, Jitsurong S, Kunthawa B, Noimay P, Noimay P, Binla A, Thamlikitkul V. 1999. Epidemiology of Burkholderia pseudomallei in Thailand. Am J Trop Med Hyg 60:458–461.
    6.
    Kaestli M, Schmid M, Mayo M, Rothballer M, Harrington G, Richardson L, Hill A, Hill J, Tuanyok A, Keim P, Hartmann A, Currie BJ. 2012. Out of the ground: aerial and exotic habitats of the melioidosis bacterium Burkholderia pseudomallei in grasses in Australia. Environ Microbiol 14:2058–2070.
    7.
    Whitmore A, Krishnaswami CS. 1912. A hitherto undescribed infective disease in Rangoon. Ind Med Gaz 47:262–267.
    8.
    Currie BJ, Ward L, Cheng AC. 2010. The epidemiology and clinical spectrum of melioidosis: 540 cases from the 20 year Darwin prospective study. PLoS Negl Trop Dis 4:e900.
    9.
    Cheng AC, Currie BJ. 2005. Melioidosis: epidemiology, pathophysiology, and management. Clin Microbiol Rev 18:383–416.
    10.
    Currie BJ, Price EP, Mayo M, Kaestli M, Theobald V, Harrington I, Harrington G, Sarovich DS. 2015. Use of whole-genome sequencing to link Burkholderia pseudomallei from air sampling to mediastinal melioidosis, Australia. Emerg Infect Dis 21:2052–2054.
    11.
    Chen P-S, Chen Y-S, Lin H-H, Liu P-J, Ni W-F, Hsueh P-T, Liang S-H, Chen C, Chen Y-L. 2015. Airborne transmission of melioidosis to humans from environmental aerosols contaminated with B. pseudomallei. PLoS Negl Trop Dis 9:e0003834.
    12.
    Stewart JD, Smith S, Binotto E, McBride WJ, Currie BJ, Hanson J. 2017. The epidemiology and clinical features of melioidosis in Far North Queensland: implications for patient management. PLoS Negl Trop Dis 11:e0005411.
    13.
    White NJ. 2003. Meliodosis. Lancet 361:1715–1722.
    14.
    Van Zandt KE, Greer MT, Gelhaus HC. 2013. Glanders: an overview of infection in humans. Orphanet J Rare Dis 8:131.
    15.
    Centers for Disease Control and Prevention. 2000. Laboratory-acquired human glanders—Maryland. MMWR Morb Mortal Wkly Rep 49:532–535.
    16.
    Currie BJ, Dance DAB, Cheng AC. 2008. The global distribution of Burkholderia pseudomallei and melioidosis: an update. Trans R Soc Trop Med Hyg 102:S1–S4.
    17.
    Limmathurotsakul D, Wongratanacheewin S, Teerawattanasook N, Wongsuvan G, Chaisuksant S, Chetchotisakd P, Chaowagul W, Day NPJ, Peacock SJ. 2010. Increasing incidence of human melioidosis in northeast Thailand. Am J Trop Med Hyg 82:1113–1117.
    18.
    Hinjoy S, Hantrakun V, Kongyu S, Kaewrakmuk J, Wangrangsimakul T, Jitsuronk S, Saengchun W, Bhengsri S, Akarachotpong T, Thamthitiwat S, Sangwichian O, Anunnatsiri S, Sermswan R, Lertmemongkolchai G, Sitthidet Tharinjaroen C, Preechasuth K, Udpaun R, Chuensombut P, Waranyasirikul N, Anudit C, Narenpitak S, Jutrakul Y, Teparrukkul P, Teerawattanasook N, Thanvisej K, Suphan A, Sukbut P, Ploddi K, Sirichotirat P, Chiewchanyon B, Rukseree K, Hongsuwan M, Wongsuwan G, Sunthornsut P, Wuthiekanun V, Sachaphimukh S, Wannapinij P, Chierakul W, Chewapreecha C, Thaipadungpanit J, Chantratita N, Korbsrisate S, Taunyok A, Dunachie S, Palittapongarnpim P, Sirisinha S, Kitphati R, Iamsirithaworn S, Chaowagul W, Chetchotisak P, Whistler T, Wongratanacheewin S, Limmathurotsakul D. 2018. Melioidosis in Thailand: present and future. Trop Med Infect Dis 3:38.
    19.
    Pearson T, Giffard P, Beckstrom-Sternberg S, Auerbach R, Hornstra H, Tuanyok A, Price EP, Glass MB, Leadem B, Beckstrom-Sternberg JS, Allan GJ, Foster JT, Wagner DM, Okinaka RT, Sim SH, Pearson O, Wu Z, Chang J, Kaul R, Hoffmaster AR, Brettin TS, Robison RA, Mayo M, Gee JE, Tan P, Currie BJ, Keim P. 2009. Phylogeographic reconstruction of a bacterial species with high levels of lateral gene transfer. BMC Biol 7:78.
    20.
    Baker A, Mayo M, Owens L, Burgess G, Norton R, McBride WJH, Currie BJ, Warner J. 2013. Biogeography of Burkholderia pseudomallei in the Torres Strait Islands of Northern Australia. J Clin Microbiol 51:2520–2525.
    21.
    Limmathurotsakul D, Golding N, Dance DA, Messina JP, Pigott DM, Moyes CL, Rolim DB, Bertherat E, Day NP, Peacock SJ, Hay SI. 2016. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol 1:15008.
    22.
    Almog Y, Yagel Y, Geffen Y, Yagupsky P. 2016. A Burkholderia pseudomallei infection imported from Eritrea to Israel. Am J Trop Med Hyg 95:997–998.
    23.
    Shaw JE, Sicree RA, Zimmet PZ. 2010. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87:4–14.
    24.
    Smith S, Hanson J, Currie BJ. 2018. Melioidosis: an Australian perspective. Trop Med Infect Dis 3:27.
    25.
    Dance DA. 1991. Melioidosis: the tip of the iceberg? Clin Microbiol Rev 4:52–60.
    26.
    Dance DAB, Limmathurotsakul D. 2018. Global burden and challenges of melioidosis. Trop Med Infect Dis 3:13.
    27.
    Mollaret HH. 1988. “L’affaire du Jardin des plantes” ou comment la melioidose fit son apparition en France. Med Mal Infect 18:643–654.
    28.
    Dance DAB. 2000. Ecology of Burkholderia pseudomallei and the interactions between environmental Burkholderia spp. and human-animal hosts. Acta Trop 74:159–168.
    29.
    Stanton AT, Fletcher W. 1925. Melioidosis: a disease of rodents communicable to man. Lancet 205:10–13.
    30.
    Ashdown LR, Clarke SG. 1992. Evaluation of culture techniques for isolation of Pseudomonas pseudomallei from soil. Appl Environ Microbiol 58:4011–4015.
    31.
    Chambon L. 1955. Isolement du bacille de Whitmore a partir du milieu exterieur. Ann Inst Pasteur 89:229–235.
    32.
    Merianos A, Patel M, Lane JM, Noonan CN, Sharrock D, Mock PA, Currie B. 1993. The 1990-1991 outbreak of melioidosis in the Northern Territory of Australia: epidemiology and environmental studies. Southeast Asian J Trop Med Public Health 24:425–435.
    33.
    Suputtamongkol Y, Chaowagul W, Chetchotisakd P, Lertpatanasuwun N, Intaranongpai S, Ruchutrakool T, Budhsarawong D, Mootsikapun P, Wuthiekanun V, Teerawatasook N, Lulitanond A. 1999. Risk factors for melioidosis and bacteremic melioidosis. Clin Infect Dis 29:408–413.
    34.
    Nasner-Posso KM, Cruz-Calderon S, Montufar-Andrade FE, Dance DA, Rodriguez-Morales AJ. 2015. Human melioidosis reported by ProMED. Int J Infect Dis 35:103–106.
    35.
    Su HP, Yang HW, Chen YL, Ferng TL, Chou YL, Chung TC, Chen CH, Chiang CS, Kuan MM, Lin HH, Chen YS. 2007. Prevalence of melioidosis in the Er-Ren River Basin, Taiwan: implications for transmission. J Clin Microbiol 45:2599–2603.
    36.
    Corkeron ML, Norton R, Nelson PN. 2010. Spatial analysis of melioidosis distribution in a suburban area. Epidemiol Infect 138:1346–1352.
    37.
    Palasatien S, Lertsirivorakul R, Royros P, Wongratanacheewin S, Sermswan RW. 2008. Soil physicochemical properties related to the presence of Burkholderia pseudomallei. Trans R Soc Trop Med Hyg 102(Suppl 1):S5–S9.
    38.
    Tong S, Yang S, Lu Z, He W. 1996. Laboratory investigation of ecological factors influencing the environmental presence of Burkholderia pseudomallei. Microbiol Immunol 40:451–453.
    39.
    Pumirat P, Cuccui J, Stabler RA, Stevens JM, Muangsombut V, Singsuksawat E, Stevens MP, Wren BW, Korbsrisate S. 2010. Global transcriptional profiling of Burkholderia pseudomallei under salt stress reveals differential effects on the Bsa type III secretion system. BMC Microbiol 10:171.
    40.
    Inglis TJ, Sagripanti J-L. 2006. Environmental factors that affect the survival and persistence of Burkholderia pseudomallei. Appl Environ Microbiol 72:6865–6875.
    41.
    Musa HI, Hassan L, Shamsuddin ZH, Panchadcharam C, Zakaria Z, Abdul Aziz S. 2016. Physicochemical properties influencing presence of Burkholderia pseudomallei in soil from small ruminant farms in peninsular Malaysia. PLoS One 11:e0162348.
    42.
    Ribolzi O, Rochelle-Newall E, Dittrich S, Auda Y, Newton PN, Rattanavong S, Knappik M, Soulileuth B, Sengtaheuanghoung O, Dance DA, Pierret A. 2016. Land use and soil type determine the presence of the pathogen Burkholderia pseudomallei in tropical rivers. Environ Sci Pollut Res Int 23:7828–7839.
    43.
    Yang HM, Chaowagul W, Sokol PA. 1991. Siderophore production by Pseudomonas pseudomallei. Infect Immun 59:776–780.
    44.
    Kvitko BH, Goodyear A, Propst KL, Dow SW, Schweizer HP. 2012. Burkholderia pseudomallei known siderophores and hemin uptake are dispensable for lethal murine melioidosis. PLoS Negl Trop Dis 6:e1715.
    45.
    Baker AL, Ezzahir J, Gardiner C, Shipton W, Warner JM. 2015. Environmental attributes influencing the distribution of Burkholderia pseudomallei in northern Australia. PLoS One 10:e0138953.
    46.
    Stopnisek N, Bodenhausen N, Frey B, Fierer N, Eberl L, Weisskopf L. 2014. Genus-wide acid tolerance accounts for the biogeographical distribution of soil Burkholderia populations. Environ Microbiol 16:1503–1512.
    47.
    Wang-Ngarm S, Chareonsudjai S, Chareonsudjai P. 2014. Physicochemical factors affecting the growth of Burkholderia pseudomallei in soil microcosm. Am J Trop Med Hyg 90:480–485.
    48.
    Hantrakun V, Rongkard P, Oyuchua M, Amornchai P, Lim C, Wuthiekanun V, Day NPJ, Peacock SJ, Limmathurotsakul D. 2016. Soil nutrient depletion is associated with the presence of Burkholderia pseudomallei. Appl Environ Microbiol 82:7086–7092.
    49.
    Ngamsang R, Potisap C, Boonmee A, Lawongsa P, Chaianunporn T, Wongratanacheewin S, Rodrigues JL, Sermswan RW. 2015. The contribution of soil physicochemical properties to the presence and genetic diversity of Burkholderia pseudomallei. Southeast Asian J Trop Med Public Health 46:38–50.
    50.
    Suebrasri T, Wang-ngarm S, Chareonsudjai P, Sermswan R, Chareonsudjai S. 2013. Seasonal variation of soil environmental characteristics affect the presence of Burkholderia pseudomallei in Khon Kaen, Thailand. Afr J Microbiol Res 7:1940–1945.
    51.
    Draper AD, Mayo M, Harrington G, Karp D, Yinfoo D, Ward L, Haslem A, Currie BJ, Kaestli M. 2010. Association of the melioidosis agent Burkholderia pseudomallei with water parameters in rural water supplies in Northern Australia. Appl Environ Microbiol 76:5305–5307.
    52.
    Zimmermann RE, Ribolzi O, Pierret A, Rattanavong S, Robinson MT, Newton PN, Davong V, Auda Y, Zopfi J, Dance DAB. 2018. Rivers as carriers and potential sentinels for Burkholderia pseudomallei in Laos. Sci Rep 8:8674.
    53.
    Currie BJ, Jacups SP. 2003. Intensity of rainfall and severity of melioidosis, Australia. Emerg Infect Dis 9:1538–1542.
    54.
    Bulterys PL, Bulterys MA, Phommasone K, Luangraj M, Mayxay M, Kloprogge S, Miliya T, Vongsouvath M, Newton PN, Phetsouvanh R, French CT, Miller JF, Turner P, Dance DAB. 2018. Climatic drivers of melioidosis in Laos and Cambodia: a 16-year case series analysis. Lancet Planet Health 2:e334–e343.
    55.
    Cheng AC, Jacups SP, Gal D, Mayo M, Currie BJ. 2006. Extreme weather events and environmental contamination are associated with case-clusters of melioidosis in the Northern Territory of Australia. Int J Epidemiol 35:323–329.
    56.
    Ko WC, Cheung BM, Tang HJ, Shih HI, Lau YJ, Wang LR, Chuang YC. 2007. Melioidosis outbreak after typhoon, southern Taiwan. Emerg Infect Dis 13:896–898.
    57.
    Sanderson C, Currie BJ. 2014. Melioidosis: a pediatric disease. Pediatr Infect Dis J 33:770–771.
    58.
    Inglis TJ, Rigby P, Robertson TA, Dutton NS, Henderson M, Chang BJ. 2000. Interaction between Burkholderia pseudomallei and Acanthamoeba species results in coiling phagocytosis, endamebic bacterial survival, and escape. Infect Immun 68:1681–1686.
    59.
    Howard K, Inglis TJ. 2005. Disinfection of Burkholderia pseudomallei in potable water. Water Res 39:1085–1092.
    60.
    Noinarin P, Chareonsudjai P, Wangsomnuk P, Wongratanacheewin S, Chareonsudjai S. 2016. Environmental free-living amoebae isolated from soil in Khon Kaen, Thailand, antagonize Burkholderia pseudomallei. PLoS One 11:e0167355.
    61.
    Cottew GS. 1950. Melioidosis in sheep in Queensland. A description of the causal organism. Aust J Exp Biol Med Sci 28:677–683.
    62.
    Rimington RA. 1962. Melioidosis in north Queensland. Med J Aust 49:50–53.
    63.
    Parameswaran U, Baird RW, Ward LM, Currie BJ. 2012. Melioidosis at Royal Darwin Hospital in the big 2009-2010 wet season: comparison with the preceding 20 years. Med J Aust 196:345–348.
    64.
    Faa AG, Holt PJ. 2002. Melioidosis in the Torres Strait Islands of Far North Queensland. Commun Dis Intell 26:279–283.
    65.
    Warner JM, Pelowa DB, Currie BJ, Hirst RG. 2007. Melioidosis in a rural community of Western Province, Papua New Guinea. Trans R Soc Trop Med Hyg 101:809–813.
    66.
    Warner JM, Pelowa DB, Gal D, Rai G, Mayo M, Currie BJ, Govan B, Skerratt LF, Hirst RG. 2008. The epidemiology of melioidosis in the Balimo region of Papua New Guinea. Epidemiol Infect 136:965–971.
    67.
    Inglis TJ, Garrow SC, Henderson M, Clair A, Sampson J, O’Reilly L, Cameron B. 2000. Burkholderia pseudomallei traced to water treatment plant in Australia. Emerg Infect Dis 6:56–59.
    68.
    Ketterer PJ, Webster WR, Shield J, Arthur RJ, Blackall PJ, Thomas AD. 1986. Melioidosis in intensive piggeries in south eastern Queensland. Aust Vet J 63:146–149.
    69.
    Currie BJ, Mayo M, Anstey NM, Donohoe P, Haase A, Kemp DJ. 2001. A cluster of melioidosis cases from an endemic region is clonal and is linked to the water supply using molecular typing of Burkholderia pseudomallei isolates. Am J Trop Med Hyg 65:177–179.
    70.
    Hampton V, Kaestli M, Mayo M, Choy JL, Harrington G, Richardson L, Benedict S, Noske R, Garnett ST, Godoy D, Spratt BG, Currie BJ. 2011. Melioidosis in birds and Burkholderia pseudomallei dispersal, Australia. Emerg Infect Dis 17:1310–1312.
    71.
    Trakulsomboon S, Vuddhakul V, Tharavichitkul P, Na-Gnam N, Suputtamongkol Y, Thamlikitkul V. 1999. Epidemiology of arabinose assimilation in burkholderia pseudomallei isolated from patients and soil in Thailand. Southeast Asian J Trop Med Public Health 30:756–759.
    72.
    Suputtamongkol Y, Hall AJ, Dance DA, Chaowagul W, Rajchanuvong A, Smith MD, White NJ. 1994. The epidemiology of melioidosis in Ubon Ratchatani, northeast Thailand. Int J Epidemiol 23:1082–1090.
    73.
    Kanaphun P, Thirawattanasuk N, Suputtamongkol Y, Naigowit P, Dance DA, Smith MD, White NJ. 1993. Serology and carriage of Pseudomonas pseudomallei: a prospective study in 1000 hospitalized children in northeast Thailand. J Infect Dis 167:230–233.
    74.
    Smith MD, Angus BJ, Wuthiekanun V, White NJ. 1997. Arabinose assimilation defines a nonvirulent biotype of Burkholderia pseudomallei. Infect Immun 65:4319–4321.
    75.
    Gilmore G, Barnes J, Ketheesan N, Norton R. 2007. Use of antigens derived from Burkholderia pseudomallei, B. thailandensis, and B. cepacia in the indirect hemagglutination assay for melioidosis. Clin Vaccine Immunol 14:1529–1531.
    76.
    Tiyawisutsri R, Peacock SJ, Langa S, Limmathurotsakul D, Cheng AC, Chierakul W, Chaowagul W, Day NPJ, Wuthiekanun V. 2005. Antibodies from patients with melioidosis recognize Burkholderia mallei but not Burkholderia thailandensis antigens in the indirect hemagglutination assay. J Clin Microbiol 43:4872–4874.
    77.
    Hantrakun V, Thaipadungpanit J, Rongkard P, Srilohasin P, Amornchai P, Langla S, Mukaka M, Chantratita N, Wuthiekanun V, Dance DAB, Day NPJ, Peacock SJ, Limmathurotsakul D. 2018. Presence of B. thailandensis and B. thailandensis expressing B. pseudomallei-like capsular polysaccharide in Thailand, and their associations with serological response to B. pseudomallei. PLoS Negl Trop Dis 12:e0006193.
    78.
    Bhengsri S, Baggett HC, Jorakate P, Kaewpan A, Prapasiri P, Naorat S, Thamthitiwat S, Tanwisaid K, Chantra S, Salika P, Dejsirilert S, Peruski LF, Maloney SA. 2011. Incidence of bacteremic melioidosis in eastern and northeastern Thailand. Am J Trop Med Hyg 85:117–120.
    79.
    Churuangsuk C, Chusri S, Hortiwakul T, Charernmak B, Silpapojakul K. 2016. Characteristics, clinical outcomes and factors influencing mortality of patients with melioidosis in southern Thailand: a 10-year retrospective study. Asian Pac J Trop Med 9:256–260.
    80.
    Trinh TT, Hoang TS, Tran DA, Trinh VT, Göhler A, Nguyen TT, Hoang SN, Krumkamp R, Nguyen LTN, May J, Doan PM, Do CD, Que TA, Steinmetz I. 2018. A simple laboratory algorithm for diagnosis of melioidosis in resource-constrained areas: a study from north-central Vietnam. Clin Microbiol Infect 24:84.e1–84.e4.
    81.
    Phuong DM, Trung TT, Breitbach K, Tuan NQ, Nubel U, Flunker G, Khang DD, Quang NX, Steinmetz I. 2008. Clinical and microbiological features of melioidosis in northern Vietnam. Trans R Soc Trop Med Hyg 102(Suppl 1):S30–S36.
    82.
    Parry CM, Wuthiekanun V, Hoa NT, Diep TS, Thao LT, Loc PV, Wills BA, Wain J, Hien TT, White NJ, Farrar JJ. 1999. Melioidosis in southern Vietnam: clinical surveillance and environmental sampling. Clin Infect Dis 29:1323–1326.
    83.
    Trinh TT, Nguyen DL, Nguyen VT, Tran XC, Le VA, Nguyen VH, Assig K, Lichtenegger S, Wagner EG, Do DC, Steinmetz I. 2018. Melioidosis in Vietnam: recently improved recognition but still an uncertain disease burden after almost a century of reporting. Trop Med Infect Dis 3:39.
    84.
    Göhler A, Trung TT, Hopf V, Kohler C, Hartleib J, Wuthiekanun V, Peacock SJ, Limmathurotsakul D, Tuanyok A, Steinmetz I. 2017. Multitarget quantitative PCR improves detection and predicts cultivability of the pathogen Burkholderia pseudomallei. Appl Environ Microbiol 83:e03212-16.
    85.
    Van Phung L, Quynh HT, Yabuuchi E, Dance DAB. 1993. Pilot study of exposure to Pseudomonas pseudomallei in northern Vietnam. Trans R Soc Trop Med Hyg 87:416.
    86.
    Stanton AT, Flectcher W, Kanagarayer K. 1924. Two cases of melioidosis. J Hyg (Lond) 23:268–276.
    87.
    Zueter AR, Yean CY, Abumarzouq M, Rahman ZA, Deris ZZ, Harun A. 2016. The epidemiology and clinical spectrum of melioidosis in a teaching hospital in a North-Eastern state of Malaysia: a fifteen-year review. BMC Infect Dis 16:333.
    88.
    How SH, Ng KH, Jamalludin AR, Shah A, Rathor Y. 2005. Melioidosis in Pahang, Malaysia. Med J Malaysia 60:606–613.
    89.
    Mohan A, Podin Y, Tai N, Chieng CH, Rigas V, Machunter B, Mayo M, Wong D, Chien SL, Tan LS, Goh C, Bantin R, Mijen A, Chua WY, Hii KC, Wong SC, Ngian HU, Wong JS, Hashim J, Currie BJ, Ooi MH. 2017. Pediatric melioidosis in Sarawak, Malaysia: epidemiological, clinical and microbiological characteristics. PLoS Negl Trop Dis 11:e0005650.
    90.
    How HS, Ng KH, Yeo HB, Tee HP, Shah A. 2005. Pediatric melioidosis in Pahang, Malaysia. J Microbiol Immunol Infect 38:314–319.
    91.
    Strauss JM, Alexander AD, Rapmund G, Gan E, Dorsey AE. 1969. Melioidosis in Malaysia. Am J Trop Med Hyg 18:703–707.
    92.
    Embi N, Suhaimi A, Mohamed R, Ismail G. 1992. Prevalence of antibodies to Pseudomonas pseudomallei exotoxin and whole cell antigens in military personnel in Sabah and Sarawak, Malaysia. Microbiol Immunol 36:899–904.
    93.
    Nathan S, Chieng S, Kingsley P, Mohan A, Podin Y, Ooi M-H, Mariappan V, Vellasamy K, Vadivelu J, Daim S, How S-H. 2018. Melioidosis in Malaysia: incidence, clinical challenges, and advances in understanding pathogenesis. Trop Med Infect Dis 3:25.
    94.
    Heng BH, Goh KT, Yap EH, Loh H, Yeo M. 1998. Epidemiological surveillance of melioidosis in Singapore. Ann Acad Med Singapore 27:478–484.
    95.
    Pang L, Harris PNA, Seiler RL, Ooi PL, Cutter J, Goh KT, Cook AR, Fisher D, Chai LYA. 2018. Melioidosis, Singapore, 2003–2014. Emerg Infect Dis 24:140.
    96.
    Tan YK, Khoo KL, Chin SP, Ong YY. 1998. Aetiology and outcome of severe community-acquired pneumonia in Singapore. Eur Respir J 12:113–115.
    97.
    Poulose V. 2008. Severe community-acquired pneumonia requiring intensive care: a study of 80 cases from Singapore. Singapore Med J 49:458–461.
    98.
    Yap EH, Chan YC, Ti TY, Thong TW, Tan AL, Yeo M, Ho LC, Singh M. 1991. Serodiagnosis of melioidosis in Singapore by the indirect haemagglutination test. Singapore Med J 32:211–213.
    99.
    Thin RNT, Groves M, Rapmund G, Mariappan M. 1971. Pseudomonas pseudomallei in the surface water of Singapore. Singap Med J 12:181–182.
    100.
    Limmathurotsakul D, Wuthiekanun V, Amornchai P, Wongsuwan G, Day NP, Peacock SJ. 2012. Effectiveness of a simplified method for isolation of Burkholderia pseudomallei from soil. Appl Environ Microbiol 78:876–877.
    101.
    Nandi T, Holden MTG, Didelot X, Mehershahi K, Boddey JA, Beacham I, Peak I, Harting J, Baybayan P, Guo Y, Wang S, How LC, Sim B, Essex-Lopresti A, Sarkar-Tyson M, Nelson M, Smither S, Ong C, Aw LT, Hoon CH, Michell S, Studholme DJ, Titball R, Chen SL, Parkhill J, Tan P. 2015. Burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination, accessory, and epigenetic profiles. Genome Res 25:129–141.
    102.
    Chantratita N, Wuthiekanun V, Limmathurotsakul D, Vesaratchavest M, Thanwisai A, Amornchai P, Tumapa S, Feil EJ, Day NP, Peacock SJ. 2008. Genetic diversity and microevolution of Burkholderia pseudomallei in the environment. PLoS Negl Trop Dis 2:e182.
    103.
    Zueter AR, Rahman ZA, Abumarzouq M, Harun A. 2018. Multilocus sequence types of clinical Burkholderia pseudomallei isolates from peninsular Malaysia and their associations with disease outcomes. BMC Infect Dis 18:5.
    104.
    Rachlin A, Dittrich S, Phommasone K, Douangnouvong A, Phetsouvanh R, Newton PN, Dance DAB. 2016. Investigation of recurrent melioidosis in Lao People’s Democratic Republic by multilocus sequence typing. Am J Trop Med Hyg 94:1208–1211.
    105.
    Pagnarith Y, Kumar V, Thaipadungpanit J, Wuthiekanun V, Amornchai P, Sin L, Day NP, Peacock SJ. 2010. Emergence of pediatric melioidosis in Siem Reap, Cambodia. Am J Trop Med Hyg 82:1106–1112.
    106.
    Overtoom R, Khieu V, Hem S, Cavailler P, Te V, Chan S, Lau P, Guillard B, Vong S. 2008. A first report of pulmonary melioidosis in Cambodia. Trans R Soc Trop Med Hyg 102(Suppl 1):S21–S25.
    107.
    Chan CK, Hyland RH, Leers WD, Hutcheon MA, Chang D. 1984. Pleuropulmonary melioidosis in a Cambodian refugee. Can Med Assoc J 131:1365–1367.
    108.
    Bory S, Daily F, Khim G, Letchford J, Sok S, Kol H, Seang Lak M, Tuseo L, Vibol C, Oeng S, Turner P. 2018. A report from the Cambodia Training Event for Awareness of Melioidosis (C-TEAM), October 2017. Trop Med Infect Dis 3:23.
    109.
    Schully KL, Berjohn CM, Prouty AM, Fitkariwala A, Som T, Sieng D, Gregory MJ, Vaughn A, Kheng S, Te V, Duplessis CA, Lawler JV, Clark DV. 2017. Melioidosis in lower provincial Cambodia: a case series from a prospective study of sepsis in Takeo Province. PLoS Negl Trop Dis 11:e0005923.
    110.
    Turner P, Kloprogge S, Miliya T, Soeng S, Tan P, Sar P, Yos P, Moore CE, Wuthiekanun V, Limmathurotsakul D, Turner C, Day NPJ, Dance DAB. 2016. A retrospective analysis of melioidosis in Cambodian children, 2009–2013. BMC Infect Dis 16:688.
    111.
    Wuthiekanun V, Pheaktra N, Putchhat H, Sin L, Sen B, Kumar V, Langla S, Peacock SJ, Day NP. 2008. Burkholderia pseudomallei antibodies in children, Cambodia. Emerg Infect Dis 14:301–303.
    112.
    Smith MD, Wuthiekanun V, Walsh AL, White NJ. 1995. Quantitative recovery of Burkholderia pseudomallei from soil in Thailand. Trans R Soc Trop Med Hyg 89:488–490.
    113.
    Vongphayloth K, Rattanavong S, Moore CE, Phetsouvanh R, Wuthiekanun V, Sengdouangphachanh A, Phouminh P, Newton PN, Buisson Y. 2012. Burkholderia pseudomallei detection in surface water in southern Laos using Moore’s swabs. Am J Trop Med Hyg 86:872–877.
    114.
    Manivanh L, Pierret A, Rattanavong S, Kounnavongsa O, Buisson Y, Elliott I, Maeght J, Xayyathip K, Silisouk J, Vongsouvath M, Phetsouvanh R, Newton PN, Lacombe G, Ribolzi O, Rochelle-Newall E, Dance DAB. 2017. Burkholderia pseudomallei in a lowland rice paddy: seasonal changes and influence of soil depth and physico-chemical properties. Sci Rep 7:3031.
    115.
    Phetsouvanh R, Phongmany S, Soukaloun D, Rasachak B, Soukhaseum V, Soukhaseum S, Frichithavong K, Khounnorath S, Pengdee B, Phiasakha K, Chu V, Luangxay K, Rattanavong S, Sisouk K, Keolouangkot V, Mayxay M, Ramsay A, Blacksell SD, Campbell J, Martinez-Aussel B, Heuanvongsy M, Bounxouei B, Thammavong C, Syhavong B, Strobel M, Peacock SJ, White NJ, Newton PN. 2006. Causes of community-acquired bacteremia and patterns of antimicrobial resistance in Vientiane, Laos. Am J Trop Med Hyg 75:978–985.
    116.
    Wuthiekanun V, Mayxay M, Chierakul W, Phetsouvanh R, Cheng AC, White NJ, Day NP, Peacock SJ. 2005. Detection of Burkholderia pseudomallei in soil within the Lao People’s Democratic Republic. J Clin Microbiol 43:923–924.
    117.
    Dance DAB, Luangraj M, Rattanavong S, Sithivong N, Vongnalaysane O, Vongsouvath M, Newton PN. 2018. Melioidosis in the Lao People’s Democratic Republic. Trop Med Infect Dis 3:21.
    118.
    Tauran PM, Wahyunie S, Saad F, Dahesihdewi A, Graciella M, Muhammad M, Lestari DC, Aryati A, Parwati I, Loho T, Pratiwi DIN, Mutiawati VK, Loesnihari R, Anggraini D, Rahayu SI, Wulan WN, Antonjaya U, Dance DAB, Currie BJ, Limmathuthurotsakul D, Arif M, Aman AT, Budayanti NNS, Iskandriati D. 2018. Emergence of melioidosis in Indonesia and today’s challenges. Trop Med Infect Dis 3:32.
    119.
    Yang S. 2000. Melioidosis research in China. Acta Trop 77:157–165.
    120.
    Chen H, Lianxu X, Xiong Z, Wei L, Xiaoli D, Duorong W, Rong H, Xiaona S, Ying L, Hong C, Xiao Z. 2015. Burkholderia pseudomallei sequence type 562 in China and Australia. Emerg Infect Dis 21:166.
    121.
    Chen Y-L, Yen Y-C, Yang C-Y, Lee MS, Ho C-K, Mena KD, Wang P-Y, Chen P-S. 2014. The concentrations of ambient Burkholderia pseudomallei during typhoon season in endemic area of melioidosis in Taiwan. PLoS Negl Trop Dis 8:e2877.
    122.
    Tipre M, Kingsley P, Smith T, Leader M, Sathiakumar N. 2018. Melioidosis in India and Bangladesh: a review of case reports. Asian Pac J Trop Med 11:320–329.
    123.
    Chowdhury RF, Jilani AMS, Barai L, Rahman T, Saha RM, Amin MR, Fatema K, Islam MK, Faiz AM, Dunachie JS, Dance AD. 2018. Melioidosis in Bangladesh: a clinical and epidemiological analysis of culture-confirmed cases. Trop Med Infect Dis 3:40.
    124.
    Jilani MSA, Robayet JAM, Mohiuddin M, Hasan MR, Ahsan CR, Haq JA. 2016. Burkholderia pseudomallei: its detection in soil and seroprevalence in Bangladesh. PLoS Negl Trop Dis 10:e0004301.
    125.
    Limmathurotsakul D, Dance DA, Wuthiekanun V, Kaestli M, Mayo M, Warner J, Wagner DM, Tuanyok A, Wertheim H, Yoke Cheng T, Mukhopadhyay C, Puthucheary S, Day NP, Steinmetz I, Currie BJ, Peacock SJ. 2013. Systematic review and consensus guidelines for environmental sampling of Burkholderia pseudomallei. PLoS Negl Trop Dis 7:e2105.
    126.
    Denny CR, Nicholls L. 1927. Melioidosis in a European. Ceylon J Sci 2:37–40.
    127.
    Corea EM, de Silva AD, Thevanesam V. 2018. Melioidosis in Sri Lanka. Trop Med Infect Dis 3:22.
    128.
    Corea EM, Merritt AJ, Ler Y-H, Thevanesam V, Inglis TJJ. 2016. Sri Lankan national melioidosis surveillance program uncovers a nationwide distribution of invasive melioidosis. Am J Trop Med Hyg 94:292–298.
    129.
    Mukhopadhyay C, Shaw T, Varghese G, Dance D. 2018. Melioidosis in South Asia (India, Nepal, Pakistan, Bhutan and Afghanistan). Trop Med Infect Dis 3:51.
    130.
    Gopalakrishnan R, Sureshkumar D, Thirunarayan MA, Ramasubramanian V. 2013. Melioidosis: an emerging infection in India. J Assoc Physicians India 61:612–614.
    131.
    Vidyalakshmi K, Lipika S, Vishal S, Damodar S, Chakrapani M. 2012. Emerging clinico-epidemiological trends in melioidosis: analysis of 95 cases from western coastal India. Int J Infect Dis 16:e491–e497.
    132.
    Vandana KE, Mukhopadhyay C, Tellapragada C, Kamath A, Tipre M, Bhat V, Sathiakumar N. 2016. Seroprevalence of Burkholderia pseudomallei among adults in coastal areas in southwestern India. PLoS Negl Trop Dis 10:e0004610.
    133.
    Peddayelachagiri BV, Paul S, Nagaraj S, Gogoi M, Sripathy MH, Batra HV. 2016. Prevalence and identification of Burkholderia pseudomallei and near-neighbor species in the Malabar coastal region of India. PLoS Negl Trop Dis 10:e0004956.
    134.
    Prakash A, Thavaselvam D, Kumar A, Kumar A, Arora S, Tiwari S, Barua A, Sathyaseelan K. 2014. Isolation, identification and characterization of Burkholderia pseudomallei from soil of coastal region of India. SpringerPlus 3:438.
    135.
    Tellapragada C, Kamthan A, Shaw T, Ke V, Kumar S, Bhat V, Mukhopadhyay C. 2016. Unravelling the molecular epidemiology and genetic diversity among Burkholderia pseudomallei isolates from South India using multi-locus sequence typing. PLoS One 11:e0168331.
    136.
    Sathkumara HD, Merritt AJ, Corea EM, Krishnananthasivam S, Natesan M, Inglis TJJ, De Silva AD. 2018. Clinical, bacteriologic, and geographic stratification of melioidosis emerges from the Sri Lankan national surveillance program. Am J Trop Med Hyg 98:607–615.
    137.
    Rolim D, Lima R, Ribeiro A, Colares R, Lima L, Rodríguez-Morales A, Montúfar F, Dance D. 2018. Melioidosis in South America. Trop Med Infect Dis 3:60.
    138.
    Benoit TJ, Blaney DD, Doker TJ, Gee JE, Elrod MG, Rolim DB, Inglis TJ, Hoffmaster AR, Bower WA, Walke HT. 2015. A review of melioidosis cases in the Americas. Am J Trop Med Hyg 93:1134–1139.
    139.
    Rolim DB, Vilar DCFL, Sousa AQ, Miralles IS, Almeida de Oliveira DC, Harnett G, O’Reilly L, Howard K, Sampson I, Inglis TJJ. 2005. Melioidosis, northeastern Brazil. Emerg Infect Dis 11:1458–1460.
    140.
    Aardema H, Luijnenburg EM, Salm EF, Bijlmer HA, Visser CE, Van’T Wout JW. 2005. Changing epidemiology of melioidosis? A case of acute pulmonary melioidosis with fatal outcome imported from Brazil. Epidemiol Infect 133:871–875.
    141.
    Inglis TJ, Rolim DB, Sousa Ade Q. 2006. Melioidosis in the Americas. Am J Trop Med Hyg 75:947–954.
    142.
    Nussbaum JJ, Hull DS, Carter M. 1980. Pseudomonas pseudomallel [sic] in an anophthalmic orbit. Arch Ophthalmol 98:1224–1225.
    143.
    Stewart T, Engelthaler DM, Blaney DD, Tuanyok A, Wangsness E, Smith TL, Pearson T, Komatsu KK, Keim P, Currie BJ, Levy C, Sunenshine R. 2011. Epidemiology and investigation of melioidosis, southern Arizona. Emerg Infect Dis 17:1286–1288.
    144.
    Hall CM, Busch JD, Shippy K, Allender CJ, Kaestli M, Mayo M, Sahl JW, Schupp JM, Colman RE, Keim P, Currie BJ, Wagner DM. 2015. Diverse Burkholderia species isolated from soils in the southern United States with no evidence of B. pseudomallei. PLoS One 10:e0143254.
    145.
    Doker TJ, Ellis EM, Hoffmaster AR, Beesley CA, Blaney DD, Walke HT, Gee JE, Elrod MG, Galloway RL, Traxler RM, Shadomy SV, Benoit TJ, Bower WA, Perez-Padilla J, Sharp TM, Rivera-Garcia B, Ryff KR, Shieh W-J, Haberling DL, Waller LA. 2014. Contact investigation of melioidosis cases reveals regional endemicity in Puerto Rico. Clin Infect Dis 60:243–250.
    146.
    Dorman SE, Vee JG, Gallin JI, Holland SM. 1998. Burkholderia pseudomallei infection in a Puerto Rican patient with chronic granulomatous disease: case report and review of occurrences in the Americas. Clin Infect Dis 26:889–894.
    147.
    Christenson B, Fuxench Z, Morales JA, Suarez-Villamil RA, Souchet LM. 2003. Severe community-acquired pneumonia and sepsis caused by Burkholderia pseudomallei associated with flooding in Puerto Rico. Bol Asoc Med P R 95:17–20.
    148.
    Hemme RR, Lopez-Ortiz R, Garcia BR, Sharp TM, Galloway RL, Elrod MG, Hunsperger EA. 2016. Serological evidence of infection with endemic human pathogens among free-ranging Old World monkeys in Puerto Rico. Am J Trop Med Hyg 94:1095–1099.
    149.
    Sanchez-Villamil JI, Torres AG. 2018. Melioidosis in Mexico, Central America, and the Caribbean. Trop Med Infect Dis 3:24.
    150.
    Chewapreecha C, Holden MTG, Vehkala M, Välimäki N, Yang Z, Harris SR, Mather AE, Tuanyok A, De Smet B, Le Hello S, Bizet C, Mayo M, Wuthiekanun V, Limmathurotsakul D, Phetsouvanh R, Spratt BG, Corander J, Keim P, Dougan G, Dance DAB, Currie BJ, Parkhill J, Peacock SJ. 2017. Global and regional dissemination and evolution of Burkholderia pseudomallei. Nat Microbiol 2:16263.
    151.
    Birnie E, Wiersinga WJ, Limmathurotsakul D, Grobusch MP. 2015. Melioidosis in Africa: should we be looking more closely? Future Microbiol 10:273–281.
    152.
    Morelli F, Smeets L, Hobijn M, Boom H. 2015. Melioidosis and renal failure in a Dutch man after a trip to Gambia. Neth J Med 73:296–298.
    153.
    Morosini MI, Quereda C, Gil H, Anda P, Núñez-Murga M, Cantón R, López-Vélez R. 2013. Melioidosis in traveler from Africa to Spain. Emerg Infect Dis 19:1656–1659.
    154.
    MacLennan IS. 1953. Melioidosis in the horse. J R Army Vet Corps 24:130–134.
    155.
    Wiersinga WJ, Birnie E, Weehuizen TA, Alabi AS, Huson MA, Huis in ‘t Veld RA, Mabala HK, Adzoda GK, Raczynski-Henk Y, Esen M, Lell B, Kremsner PG, Visser CE, Wuthiekanun V, Peacock SJ, van der Ende A, Limmathurotsakul D, Grobusch MP. 2015. Clinical, environmental, and serologic surveillance studies of melioidosis in Gabon, 2012–2013. Emerg Infect Dis 21:40.
    156.
    Salam AP, Khan N, Malnick H, Kenna DTD, Dance DAB, Klein JL. 2011. Melioidosis acquired by traveler to Nigeria. Emerg Infect Dis 17:1296–1298.
    157.
    Rakotondrasoa A, Issack IM, Garin B, Biot F, Valade E, Wattiau P, Allou N, Belmonte O, Bibi J, Price PE, Collard J-M. 2018. Melioidosis in the western Indian Ocean and the importance of improving diagnosis, surveillance, and molecular typing. Trop Med Infect Dis 3:30.
    158.
    Sarovich DS, Garin B, De Smet B, Kaestli M, Mayo M, Vandamme P, Jacobs J, Lompo P, Tahita MC, Tinto H, Djaomalaza I, Currie BJ, Price EP. 2016. Phylogenomic analysis reveals an Asian origin for African Burkholderia pseudomallei and further supports melioidosis endemicity in Africa. mSphere 1:e00089-15.
    159.
    Steinmetz I, Wagner EG, Kanyala E, Sawadogo M, Soumeya H, Teferi M, Andargie E, Yeshitela B, Yaba Atsé-Achi L, Sanogo M, Bonfoh B, Rakotozandrindrainy R, Pongombo Shongo C, Shongoya Pongombo M, Kasamba Ilunga E, Lichtenegger S, Assig K, May J, Bertherat E, Owusu M, Owusu-Dabo E, Adu-Sarkodie Y. 2018. Melioidosis in Africa: time to uncover the true disease load. Trop Med Infect Dis 3:62.
    160.
    Govan B. 2012. Molecular characterisation and classification of Burkholderia pseudomallei, p 60–67. In Ketheesan N (ed), Melioidosis: a century of observation and research. Elsevier, Amsterdam, the Netherlands.
    161.
    Yabuuchi E, Kosako Y, Oyaizu H, Yano I, Hotta H, Hashimoto Y, Ezaki T, Arakawa M. 1992. Proposal of Burkholderia gen. nov. and transfer of seven species of the genus Pseudomonas homology group II to the new genus, with the type species Burkholderia cepacia (Palleroni and Holmes 1981) comb. nov. Microbiol Immunol 36:1251–1275.
    162.
    Redfearn MS, Palleroni NJ, Stanier RY. 1966. A comparative study of Pseudomonas pseudomallei and Bacillus mallei. J Gen Microbiol 43:293–313.
    163.
    Pumpuang A, Chantratita N, Wikraiphat C, Saiprom N, Day NPJ, Peacock SJ, Wuthiekanun V. 2011. Survival of Burkholderia pseudomallei in distilled water for 16 years. Trans R Soc Trop Med Hyg 105:598–600.
    164.
    Wuthiekanun V, Dance DAB, Wattanagoon Y, Supputtamongkol Y, Chaowagul W, White NJ. 1990. The use of selective media for the isolation of Pseudomonas pseudomallei in clinical practice. J Med Microbiol 33:121–126.
    165.
    White NJ, Dance DAB. 1988. Clinical and laboratory studies of malaria and melioidosis. Trans R Soc Trop Med Hyg 82:15–20.
    166.
    Hassan MRA, Pani SP, Peng NP, Voralu K, Vijayalakshmi N, Mehanderkar R, Aziz NA, Michael E. 2010. Incidence, risk factors and clinical epidemiology of melioidosis: a complex socio-ecological emerging infectious disease in the Alor Setar region of Kedah, Malaysia. BMC Infect Dis 10:302.
    167.
    Kingsley PV, Leader M, Nagodawithana NS, Tipre M, Sathiakumar N. 2016. Melioidosis in Malaysia: a review of case reports. PLoS Negl Trop Dis 10:e0005182.
    168.
    Pagalavan L. 2005. Melioidosis: the Johor Bahru experience. Med J Malaysia 60:599–605.
    169.
    Tiangpitayakorn C, Songsivilai S, Piyasangthong N, Dharakul T. 1997. Speed of detection of Burkholderia pseudomallei in blood cultures and its correlation with the clinical outcome. Am J Trop Med Hyg 57:96–99.
    170.
    Teerawattanasook N, Limmathurotsakul D, Day NPJ, Wuthiekanun V. 2014. Failure of Burkholderia pseudomallei to grow in an automated blood culture system. Am J Trop Med Hyg 91:1173–1175.
    171.
    Jorakate P, Higdon M, Kaewpan A, Makprasert S, Yuenprakhon S, Tawisaid K, Dejsirilert S, Whistler T, Baggett HC. 2015. Contribution of the BacT/Alert MB Mycobacterium bottle to bloodstream infection surveillance in Thailand: added yield for Burkholderia pseudomallei. J Clin Microbiol 53:910–914.
    172.
    Udayan U, Dias M. 2014. Evaluation of BACTEC™ blood culture system for culture of normally sterile body fluids. Indian J Crit Care Med 18:829–830.
    173.
    Chantratita N, Tandhavanant S, Wongsuvan G, Wuthiekanun V, Teerawattanasook N, Day NPJ, Limmathurotsakul D, Peacock SJ. 2013. Rapid detection of Burkholderia pseudomallei in blood cultures using a monoclonal antibody-based immunofluorescent assay. Am J Trop Med Hyg 89:971–972.
    174.
    Limmathurotsakul D, Wuthiekanun V, Chierakul W, Cheng AC, Maharjan B, Chaowagul W, White NJ, Day NP, Peacock SJ. 2005. Role and significance of quantitative urine cultures in diagnosis of melioidosis. J Clin Microbiol 43:2274–2276.
    175.
    Cheng AC, Wuthiekanun V, Limmathurosakul D, Wongsuvan G, Day NP, Peacock SJ. 2006. Role of selective and nonselective media for isolation of Burkholderia pseudomallei from throat swabs of patients with melioidosis. J Clin Microbiol 44:2316.
    176.
    Hoffmaster AR, AuCoin D, Baccam P, Baggett HC, Baird R, Bhengsri S, Blaney DD, Brett PJ, Brooks TJ, Brown KA, Chantratita N, Cheng AC, Dance DA, Decuypere S, Defenbaugh D, Gee JE, Houghton R, Jorakate P, Lertmemongkolchai G, Limmathurotsakul D, Merlin TL, Mukhopadhyay C, Norton R, Peacock SJ, Rolim DB, Simpson AJ, Steinmetz I, Stoddard RA, Stokes MM, Sue D, Tuanyok A, Whistler T, Wuthiekanun V, Walke HT. 2015. Melioidosis diagnostic workshop, 2013. Emerg Infect Dis doi:
    177.
    Gilad J, Schwartz D, Amsalem Y. 2007. Clinical features and laboratory diagnosis of infection with the potential bioterrorism agents Burkholderia mallei and Burkholderia pseudomallei. Int J Biomed Sci 3:144–152.
    178.
    Ashdown LR. 1979. An improved screening technique for isolation of Pseudomonas pseudomallei from clinical specimens. Pathology 11:293–297.
    179.
    Rogul M, Carr SR. 1972. Variable ammonia production among smooth and rough strains of Pseudomonas pseudomallei: resemblance to bacteriocin production. J Bacteriol 112:372–380.
    180.
    Howard K, Inglis TJJ. 2003. Novel selective medium for isolation of Burkholderia pseudomallei. J Clin Microbiol 41:3312–3316.
    181.
    Podin Y, Sarovich DS, Price EP, Kaestli M, Mayo M, Hii K, Ngian H, Wong S, Wong I, Wong J, Mohan A, Ooi M, Fam T, Wong J, Tuanyok A, Keim P, Giffard PM, Currie BJ. 2014. Burkholderia pseudomallei isolates from Sarawak, Malaysian Borneo, are predominantly susceptible to aminoglycosides and macrolides. Antimicrob Agents Chemother 58:162–166.
    182.
    Francis A, Aiyar S, Yean CY, Naing L, Ravichandran M. 2006. An improved selective and differential medium for the isolation of Burkholderia pseudomallei from clinical specimens. Diagn Microbiol Infect Dis 55:95–99.
    183.
    Peacock SJ, Chieng G, Cheng AC, Dance DAB, Amornchai P, Wongsuvan G, Teerawattanasook N, Chierakul W, Day NPJ, Wuthiekanun V. 2005. Comparison of Ashdown’s medium, Burkholderia cepacia medium, and Burkholderia pseudomallei selective agar for clinical isolation of Burkholderia pseudomallei. J Clin Microbiol 43:5359–5361.
    184.
    Goodyear A, Strange L, Rholl DA, Silisouk J, Dance DAB, Schweizer HP, Dow S. 2013. An improved selective culture medium enhances the isolation of Burkholderia pseudomallei from contaminated specimens. Am J Trop Med Hyg 89:973–982.
    185.
    Roesnita B, Tay ST, Puthucheary SD, Sam IC. 2012. Diagnostic use of Burkholderia pseudomallei selective media in a low prevalence setting. Trans R Soc Trop Med Hyg 106:131–133.
    186.
    Wuthiekanun V, Suputtamongkol Y, Simpson AJH, Kanaphun P, White NJ. 2001. Value of throat swab in diagnosis of melioidosis. J Clin Microbiol 39:3801–3802.
    187.
    Walsh AL, Wuthiekanun V, Smith MD, Suputtamongkol Y, White NJ. 1995. Selective broths for the isolation of Pseudomonas pseudomallei from clinical samples. Trans R Soc Trop Med Hyg 89:124.
    188.
    Limmathurotsakul D, Jamsen K, Arayawichanont A, Simpson JA, White LJ, Lee SJ, Wuthiekanun V, Chantratita N, Cheng A, Day NPJ, Verzilli C, Peacock SJ. 2010. Defining the true sensitivity of culture for the diagnosis of melioidosis using Bayesian latent class models. PLoS One 5:e12485.
    189.
    Wongsuvan G, Limmathurotsakul D, Wannapasni S, Chierakul W, Teerawattanasook N, Wuthiekanun V. 2009. Lack of correlation of Burkholderia pseudomallei quantities in blood, urine, sputum and pus. Southeast Asian J Trop Med Public Health 40:781–784.
    190.
    Hemarajata P, Baghdadi JD, Hoffman R, Humphries RM. 2016. Burkholderia pseudomallei: challenges for the clinical microbiology laboratory. J Clin Microbiol 54:2866–2873.
    191.
    Eickhoff TC, Bennett JV, Hayes PS, Feeley J. 1970. Pseudomonas pseudomallei: susceptibility to chemotherapeutic agents. J Infect Dis 121:95–102.
    192.
    Dance DA, Wuthiekanun V, Naigowit P, White NJ. 1989. Identification of Pseudomonas pseudomallei in clinical practice: use of simple screening tests and API 20NE. J Clin Pathol 42:645–648.
    193.
    Hodgson K, Engler C, Govan B, Ketheesan N, Norton R. 2009. Comparison of routine bench and molecular diagnostic methods in identification of Burkholderia pseudomallei. J Clin Microbiol 47:1578–1580.
    194.
    Anuntagool N, Naigowit P, Petkanchanapong V, Aramsri P, Panichakul T, Sirisinha S. 2000. Monoclonal antibody-based rapid identification of burkholderia pseudomallei in blood culture fluid from patients with community-acquired septicaemia. J Med Microbiol 49:1075–1078.
    195.
    Dharakul T, Songsivilai S, Smithikarn S, Thepthai C, Leelaporn A. 1999. Rapid identification of Burkholderia pseudomallei in blood cultures by latex agglutination using lipopolysaccharide-specific monoclonal antibody. Am J Trop Med Hyg 61:658–662.
    196.
    Pongsunk S, Thirawattanasuk N, Piyasangthong N, Ekpo P. 1999. Rapid identification of Burkholderia pseudomallei in blood cultures by a monoclonal antibody assay. J Clin Microbiol 37:3662–3667.
    197.
    Inglis TJ, Merritt A, Chidlow G, Aravena-Roman M, Harnett G. 2005. Comparison of diagnostic laboratory methods for identification of Burkholderia pseudomallei. J Clin Microbiol 43:2201–2206.
    198.
    Wuthiekanun V, Anuntagool N, White NJ, Sirisinha S. 2002. Short report: a rapid method for the differentiation of Burkholderia pseudomallei and Burkholderia thailandensis. Am J Trop Med Hyg 66:759–761.
    199.
    Duval BD, Elrod MG, Gee JE, Chantratita N, Tandhavanant S, Limmathurotsakul D, Hoffmaster AR. 2014. Evaluation of a latex agglutination assay for the identification of Burkholderia pseudomallei and Burkholderia mallei. Am J Trop Med Hyg 90:1043–1046.
    200.
    Dulsuk A, Paksanont S, Sangchankoom A, Ekchariyawat P, Phunpang R, Jutrakul Y, Chantratita N, West TE. 2017. Validation of a monoclonal antibody-based immunofluorescent assay to detect Burkholderia pseudomallei in blood cultures. Trans R Soc Trop Med Hyg 110:670–672.
    201.
    Tandhavanant S, Wongsuvan G, Wuthiekanun V, Teerawattanasook N, Day NPJ, Limmathurotsakul D, Peacock SJ, Chantratita N. 2013. Monoclonal antibody-based immunofluorescence microscopy for the rapid identification of Burkholderia pseudomallei in clinical specimens. Am J Trop Med Hyg 89:165–168.
    202.
    Houghton RL, Reed DE, Hubbard MA, Dillon MJ, Chen H, Currie BJ, Mayo M, Sarovich DS, Theobald V, Limmathurotsakul D, Wongsuvan G, Chantratita N, Peacock SJ, Hoffmaster AR, Duval B, Brett PJ, Burtnick MN, AuCoin DP. 2014. Development of a prototype lateral flow immunoassay (LFI) for the rapid diagnosis of melioidosis. PLoS Negl Trop Dis 8:e2727.
    203.
    Price EP, Sarovich DS, Mayo M, Tuanyok A, Drees KP, Kaestli M, Beckstrom-Sternberg SM, Babic-Sternberg JS, Kidd TJ, Bell SC, Keim P, Pearson T, Currie BJ. 2013. Within-host evolution of Burkholderia pseudomallei over a twelve-year chronic carriage infection. mBio 4:e00388-13.
    204.
    Cuccui J, Milne TS, Harmer N, George AJ, Harding SV, Dean RE, Scott AE, Sarkar-Tyson M, Wren BW, Titball RW, Prior JL. 2012. Characterization of the Burkholderia pseudomallei K96243 capsular polysaccharide I coding region. Infect Immun 80:1209–1221.
    205.
    Robertson G, Sorenson A, Govan B, Ketheesan N, Houghton R, Chen H, AuCoin D, Dillon M, Norton R. 2015. Rapid diagnostics for melioidosis: a comparative study of a novel lateral flow antigen detection assay. J Med Microbiol 64:845–848.
    206.
    Woods KL, Boutthasavong L, NicFhogartaigh C, Lee SJ, Davong V, AuCoin DP, Dance DAB. 2018. Evaluation of a rapid diagnostic test for detection of Burkholderia pseudomallei in the Lao People’s Democratic Republic. J Clin Microbiol 56:e02002-17.
    207.
    Suttisunhakul V, Wuthiekanun V, Brett PJ, Khusmith S, Day NP, Burtnick MN, Limmathurotsakul D, Chantratita N. 2016. Development of rapid enzyme-linked immunosorbent assays for detection of antibodies to Burkholderia pseudomallei. J Clin Microbiol 54:1259–1268.
    208.
    Wuthiekanun V, Chierakul W, Langa S, Chaowagul W, Panpitpat C, Saipan P, Thoujaikong T, Day NP, Peacock SJ. 2006. Development of antibodies to Burkholderia pseudomallei during childhood in melioidosis-endemic northeast Thailand. Am J Trop Med Hyg 74:1074–1075.
    209.
    Suttisunhakul V, Chantratita N, Wikraiphat C, Wuthiekanun V, Douglas Z, Day NPJ, Limmathurotsakul D, Brett PJ, Burtnick MN. 2015. Evaluation of polysaccharide-based latex agglutination assays for the rapid detection of antibodies to Burkholderia pseudomallei. Am J Trop Med Hyg 93:542–546.
    210.
    Kritsiriwuthinan K, Wajanarogana S, Choosang K, Homsian J, Rerkthanom S. 2018. Production and evaluation of recombinant Burkholderia pseudomallei GroEL and OmpA proteins for serodiagnosis of melioidosis. Acta Trop 178:333–339.
    211.
    Alexander AD, Huxsoll DL, Warner AR, Jr, Shepler V, Dorsey A. 1970. Serological diagnosis of human melioidosis with indirect hemagglutination and complement fixation tests. Appl Microbiol 20:825–833.
    212.
    Harris PN, Ketheesan N, Owens L, Norton RE. 2009. Clinical features that affect indirect-hemagglutination-assay responses to Burkholderia pseudomallei. Clin Vaccine Immunol 16:924–930.
    213.
    Leelarasamee A. 1985. Diagnostic value of indirect hemagglutination method for melioidosis in Thailand. J Infect Dis Antimicrob Agents 2:213–214.
    214.
    Appassakij H, Silpapojakul KR, Wansit R, Pornpatkul M. 1990. Diagnostic value of the indirect hemagglutination test for melioidosis in an endemic area. Am J Trop Med Hyg 42:248–253.
    215.
    Chaichana P, Jenjaroen K, Amornchai P, Chumseng S, Langla S, Rongkard P, Sumonwiriya M, Jeeyapant A, Chantratita N, Teparrukkul P, Limmathurotsakul D, Day NPJ, Wuthiekanun V, Dunachie SJ. 2018. Antibodies in melioidosis: the role of the indirect hemagglutination assay in evaluating patients and exposed populations. Am J Trop Med Hyg 99:1378–1385.
    216.
    Cheng AC, O’Brien M, Freeman K, Lum G, Currie BJ. 2006. Indirect hemagglutination assay in patients with melioidosis in northern Australia. Am J Trop Med Hyg 74:330–334.
    217.
    Lazzaroni SM, Barnes JL, Williams NL, Govan BL, Norton RE, LaBrooy JT, Ketheesan N. 2008. Seropositivity to Burkholderia pseudomallei does not reflect the development of cell-mediated immunity. Trans R Soc Trop Med Hyg 102(Suppl 1):S66–S70.
    218.
    Ashdown LR, Johnson RW, Koehler JM, Cooney CA. 1989. Enzyme-linked immunosorbent assay for the diagnosis of clinical and subclinical melioidosis. J Infect Dis 160:253–260.
    219.
    Cuzzubbo AJ, Chenthamarakshan V, Vadivelu J, Puthucheary SD, Rowland D, Devine PL. 2000. Evaluation of a new commercially available immunoglobulin M and immunoglobulin G immunochromatographic test for diagnosis of melioidosis infection. J Clin Microbiol 38:1670–1671.
    220.
    Chuah SC, Gilmore G, Norton RE. 2005. Rapid serological diagnosis of melioidosis: an evaluation of a prototype immunochromatographic test. Pathology 37:169–171.
    221.
    O’Brien M, Freeman K, Lum G, Cheng AC, Jacups SP, Currie BJ. 2004. Further evaluation of a rapid diagnostic test for melioidosis in an area of endemicity. J Clin Microbiol 42:2239–2240.
    222.
    Chantratita N, Lertmemongkolchai G, Wuthiekanun V, Norton R. 2012. The serological diagnosis of melioidosis, p 160–167. In Ketheesan N (ed), Melioidosis: a century of observation and research. Elsevier, Amsterdam, the Netherlands.
    223.
    Burtnick MN, Brett PJ, Harding SV, Ngugi SA, Ribot WJ, Chantratita N, Scorpio A, Milne TS, Dean RE, Fritz DL, Peacock SJ, Prior JL, Atkins TP, Deshazer D. 2011. The cluster 1 type VI secretion system is a major virulence determinant in Burkholderia pseudomallei. Infect Immun 79:1512–1525.
    224.
    Chen Y, Wong J, Sun GW, Liu Y, Tan G-YG, Gan Y-H. 2011. Regulation of type VI secretion system during Burkholderia pseudomallei Infection. Infect Immun 79:3064–3073.
    225.
    Chieng S, Mohamed R, Nathan S. 2015. Transcriptome analysis of Burkholderia pseudomallei T6SS identifies Hcp1 as a potential serodiagnostic marker. Microb Pathog 79:47–56.
    226.
    Pumpuang A, Dunachie SJ, Phokrai P, Jenjaroen K, Sintiprungrat K, Boonsilp S, Brett PJ, Burtnick MN, Chantratita N. 2017. Comparison of O-polysaccharide and hemolysin co-regulated protein as target antigens for serodiagnosis of melioidosis. PLoS Negl Trop Dis 11:e0005499.
    227.
    Phokrai P, Karoonboonyanan W, Thanapattarapairoj N, Promkong C, Dulsuk A, Koosakulnirand S, Canovali S, Indrawattana N, Jutrakul Y, Wuthiekanun V, Limmathurotsakul D, Brett PJ, Burtnick MN, Lertmemongkolchai G, Chantratita N. 2018. A rapid immunochromatography test based on Hcp1 is a potential point-of-care test for serological diagnosis of melioidosis. J Clin Microbiol 56:e00346-18.
    228.
    Dharakul T, Songsivilai S, Anuntagool N, Chaowagul W, Wongbunnate S, Intachote P, Sirisinha S. 1997. Diagnostic value of an antibody enzyme-linked immunosorbent assay using affinity-purified antigen in an area endemic for melioidosis. Am J Trop Med Hyg 56:418–423.
    229.
    Kunakorn M, Boonma P, Khupulsup K, Petchclai B. 1990. Enzyme-linked immunosorbent assay for immunoglobulin M specific antibody for the diagnosis of melioidosis. J Clin Microbiol 28:1249–1253.
    230.
    Inglis TJ, Chiang D, Lee GS, Chor-Kiang L. 1998. Potential misidentification of Burkholderia pseudomallei by API 20NE. Pathology 30:62–64.
    231.
    Lowe P, Engler C, Norton R. 2002. Comparison of automated and nonautomated systems for identification of Burkholderia pseudomallei. J Clin Microbiol 40:4625–4627.
    232.
    Amornchai P, Chierakul W, Wuthiekanun V, Mahakhunkijcharoen Y, Phetsouvanh R, Currie BJ, Newton PN, van Vinh Chau N, Wongratanacheewin S, Day NP, Peacock SJ. 2007. Accuracy of Burkholderia pseudomallei identification using the API 20NE system and a latex agglutination test. J Clin Microbiol 45:3774–3776.
    233.
    Zong Z, Wang X, Deng Y, Zhou T. 2012. Misidentification of Burkholderia pseudomallei as Burkholderia cepacia by the VITEK 2 system. J Med Microbiol 61:1483–1484.
    234.
    Zakharova I, Lopasteyskaya Y, Toporkov A, Viktorov D. 2018. Influence of biochemical features of Burkholderia pseudomallei strains on identification reliability by Vitek 2 system. J Glob Infect Dis 10:7–10.
    235.
    Lowe P, Haswell H, Lewis K. 2006. Use of various common isolation media to evaluate the new VITEK 2 colorimetric GN card for identification of Burkholderia pseudomallei. J Clin Microbiol 44:854–856.
    236.
    Podin Y, Kaestli M, McMahon N, Hennessy J, Ngian HU, Wong JS, Mohana A, Wong SC, William T, Mayo M, Baird RW, Currie BJ. 2013. Reliability of automated biochemical identification of Burkholderia pseudomallei is regionally dependent. J Clin Microbiol 51:3076–3078.
    237.
    Brett PJ, DeShazer D, Woods DE. 1998. Burkholderia thailandensis sp. nov., a Burkholderia pseudomallei-like species. Int J Syst Bacteriol 4:317–320.
    238.
    Koh TH, Yong Ng LS, Foon Ho JL, Sng L-H, Wang GCY, Valentine Tzer Pin Lin R. 2003. Automated identification systems and Burkholderia pseudomallei. J Clin Microbiol 41:1809.
    239.
    Weissert C, Dollenmaier G, Rafeiner P, Riehm J, Schultze D. 2009. Burkholderia pseudomallei misidentified by automated system. Emerg Infect Dis 15:1799.
    240.
    Inglis TJ, Aravena-Roman M, Ching S, Croft K, Wuthiekanun V, Mee BJ. 2003. Cellular fatty acid profile distinguishes Burkholderia pseudomallei from avirulent Burkholderia thailandensis. J Clin Microbiol 41:4812–4814.
    241.
    Welker M, Moore ER. 2011. Applications of whole-cell matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry in systematic microbiology. Syst Appl Microbiol 34:2–11.
    242.
    Krásný L, Hynek R, Hochel I. 2013. Identification of bacteria using mass spectrometry techniques. Int J Mass Spectrom 353:67–79.
    243.
    Holland RD, Wilkes JG, Rafii F, Sutherland JB, Persons CC, Voorhees KJ, Lay JO, Jr. 1996. Rapid identification of intact whole bacteria based on spectral patterns using matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 10:1227–1232.
    244.
    Gassiep I, Armstrong M, Norton RE. 2019. Identification of Burkholderia pseudomallei by use of the Vitek mass spectrometer. J Clin Microbiol 57:e00081-19.
    245.
    Karger A, Stock R, Ziller M, Elschner MC, Bettin B, Melzer F, Maier T, Kostrzewa M, Scholz HC, Neubauer H, Tomaso H. 2012. Rapid identification of Burkholderia mallei and Burkholderia pseudomallei by intact cell matrix-assisted laser desorption/ionisation mass spectrometric typing. BMC Microbiol 12:229.
    246.
    Wang H, Chen YL, Teng SH, Xu ZP, Xu YC, Hsueh PR. 2016. Evaluation of the Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight mass spectrometry system for identification of clinical and environmental isolates of Burkholderia pseudomallei. Front Microbiol 7:415.
    247.
    Luo Y, Siu GK, Yeung AS, Chen JH, Ho PL, Leung KW, Tsang JL, Cheng VC, Guo L, Yang J, Ye L, Yam WC. 2015. Performance of the VITEK MS matrix-assisted laser desorption ionization-time of flight mass spectrometry system for rapid bacterial identification in two diagnostic centres in China. J Med Microbiol 64:18–24.
    248.
    Dingle TC, Butler-Wu SM, Abbott AN. 2014. Accidental exposure to Burkholderia pseudomallei in the laboratory in the era of matrix-assisted laser desorption ionization–time of flight mass spectrometry. J Clin Microbiol 52:3490–3491.
    249.
    Walewski V, Mechai F, Billard-Pomares T, Juguet W, Jaureguy F, Picard B, Tandjaoui-Lambiotte Y, Carbonnelle E, Bouchaud O. 2016. MALDI-TOF MS contribution to diagnosis of melioidosis in a nonendemic country in three French travellers. New Microbes New Infect 12:31–34.
    250.
    Jang HR, Lee CW, Ok SJ, Kim MJ, Bae MJ, Song S, Yi J, Kim KH. 2015. Melioidosis presenting as a mycotic aneurysm in a Korean patient, diagnosed by 16S rRNA sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Int J Infect Dis 38:62–64.
    251.
    Niyompanich S, Jaresitthikunchai J, Srisanga K, Roytrakul S, Tungpradabkul S. 2014. Source-identifying biomarker ions between environmental and clinical Burkholderia pseudomallei using whole-cell matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). PLoS One 9:e99160.
    252.
    Cox CR, Saichek NR, Schweizer HP, Voorhees KJ. 2014. Rapid Burkholderia pseudomallei identification and antibiotic resistance determination by bacteriophage amplification and MALDI-TOF MS. Bacteriophage 4:e29011.
    253.
    Inglis TJ, Healy PE, Fremlin LJ, Golledge CL. 2012. Use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis for rapid confirmation of Burkholderia pseudomallei in septicemic melioidosis. Am J Trop Med Hyg 86:1039–1042.
    254.
    Suttisunhakul V, Pumpuang A, Ekchariyawat P, Wuthiekanun V, Elrod MG, Turner P, Currie BJ, Phetsouvanh R, Dance DA, Limmathurotsakul D, Peacock SJ, Chantratita N. 2017. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for the identification of Burkholderia pseudomallei from Asia and Australia and differentiation between Burkholderia species. PLoS One 12:e0175294.
    255.
    Rudrik JT, Soehnlen MK, Perry MJ, Sullivan MM, Reiter-Kintz W, Lee PA, Pettit D, Tran A, Swaney E. 2017. Safety and accuracy of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of highly pathogenic organisms. J Clin Microbiol 55:3513–3529.
    256.
    Cunningham SA, Patel R. 2013. Importance of using Bruker’s security-relevant library for Biotyper identification of Burkholderia pseudomallei, Brucella species, and Francisella tularensis. J Clin Microbiol 51:1639–1640.
    257.
    Cunningham SA, Patel R. 2015. Standard matrix-assisted laser desorption ionization-time of flight mass spectrometry reagents may inactivate potentially hazardous bacteria. J Clin Microbiol 53:2788–2789.
    258.
    Merritt A, Inglis TJJ, Chidlow G, Harnett G. 2006. PCR-based identification of Burkholderia pseudomallei. Rev Inst Med Trop Sao Paulo 48:239–244.
    259.
    Price EP, Dale JL, Cook JM, Sarovich DS, Seymour ML, Ginther JL, Kaufman EL, Beckstrom-Sternberg SM, Mayo M, Kaestli M, Glass MB, Gee JE, Wuthiekanun V, Warner JM, Baker A, Foster JT, Tan P, Tuanyok A, Limmathurotsakul D, Peacock SJ, Currie BJ, Wagner DM, Keim P, Pearson T. 2012. Development and validation of Burkholderia pseudomallei-specific real-time PCR assays for clinical, environmental or forensic detection applications. PLoS One 7:e37723.
    260.
    Lowe CW, Satterfield BA, Nelson DB, Thiriot JD, Heder MJ, March JK, Drake DS, Lew CS, Bunnell AJ, Moore ES, O’Neill KL, Robison RA. 2016. A quadruplex real-time PCR assay for the rapid detection and differentiation of the most relevant members of the B. pseudomallei complex: B. mallei, B. pseudomallei, and B. thailandensis. PLoS One 11:e0164006.
    261.
    U’Ren JM, Van Ert MN, Schupp JM, Easterday WR, Simonson TS, Okinaka RT, Pearson T, Keim P. 2005. Use of a real-time PCR TaqMan assay for rapid identification and differentiation of Burkholderia pseudomallei and Burkholderia mallei. J Clin Microbiol 43:5771–5774.
    262.
    Bowers JR, Engelthaler DM, Ginther JL, Pearson T, Peacock SJ, Tuanyok A, Wagner DM, Currie BJ, Keim PS. 2010. BurkDiff: a real-time PCR allelic discrimination assay for Burkholderia pseudomallei and B. mallei. PLoS One 5:e15413.
    263.
    Novak RT, Glass MB, Gee JE, Gal D, Mayo MJ, Currie BJ, Wilkins PP. 2006. Development and evaluation of a real-time PCR assay targeting the type III secretion system of Burkholderia pseudomallei. J Clin Microbiol 44:85–90.
    264.
    Thibault FM, Valade E, Vidal DR. 2004. Identification and discrimination of Burkholderia pseudomallei, B. mallei, and B. thailandensis by real-time PCR targeting type III secretion system genes. J Clin Microbiol 42:5871–5874.
    265.
    Meumann EM, Novak RT, Gal D, Kaestli ME, Mayo M, Hanson JP, Spencer E, Glass MB, Gee JE, Wilkins PP, Currie BJ. 2006. Clinical evaluation of a type III secretion system real-time PCR assay for diagnosing melioidosis. J Clin Microbiol 44:3028–3030.
    266.
    Gal D, Mayo M, Spencer E, Cheng AC, Currie BJ. 2005. Short report: application of a polymerase chain reaction to detect Burkholderia pseudomallei in clinical specimens from patients with suspected melioidosis. Am J Trop Med Hyg 73:1162–1164.
    267.
    Walsh AL, Smith MD, Wuthiekanun V, Suputtamongkol Y, Chaowagul W, Dance DA, Angus B, White NJ. 1995. Prognostic significance of quantitative bacteremia in septicemic melioidosis. Clin Infect Dis 21:1498–1500.
    268.
    Kluge RM, Du Pont HL. 1973. Factors affecting mortality of patients with bacteremia. Crit Care Med 1:291.
    269.
    DuPont HL, Spink WW. 1969. Infections due to gram-negative organisms: an analysis of 860 patients with bacteremia at the University of Minnesota Medical Center, 1958–1966. Medicine 48:307–332.
    270.
    Wuthiekanun V, Limmathurotsakul D, Wongsuvan G, Chierakul W, Teerawattanasook N, Teparrukkul P, Day NP, Peacock SJ. 2007. Quantitation of B. pseudomallei in clinical samples. Am J Trop Med Hyg 77:812–813.
    271.
    Zakharova I, Teteryatnikova N, Toporkov A, Viktorov D. 2017. Development of a multiplex PCR assay for the detection and differentiation of Burkholderia pseudomallei, Burkholderia mallei, Burkholderia thailandensis, and Burkholderia cepacia complex. Acta Trop 174:1–8.
    272.
    Lee MA, Wang D, Yap EH. 2005. Detection and differentiation of Burkholderia pseudomallei, Burkholderia mallei and Burkholderia thailandensis by multiplex PCR. FEMS Immunol Med Microbiol 43:413–417.
    273.
    Bachert BA, Choi SJ, Snyder AK, Rio RV, Durney BC, Holland LA, Amemiya K, Welkos SL, Bozue JA, Cote CK, Berisio R, Lukomski S. 2015. A unique set of the Burkholderia collagen-like proteins provides insight into pathogenesis, genome evolution and niche adaptation, and infection detection. PLoS One 10:e0137578.
    274.
    Podnecky NL, Elrod MG, Newton BR, Dauphin LA, Shi J, Chawalchitiporn S, Baggett HC, Hoffmaster AR, Gee JE. 2013. Comparison of DNA extraction kits for detection of Burkholderia pseudomallei in spiked human whole blood using real-time PCR. PLoS One 8:e58032.
    275.
    Richardson LJ, Kaestli M, Mayo M, Bowers JR, Tuanyok A, Schupp J, Engelthaler D, Wagner DM, Keim PS, Currie BJ. 2012. Towards a rapid molecular diagnostic for melioidosis: comparison of DNA extraction methods from clinical specimens. J Microbiol Methods 88:179–181.
    276.
    Merk S, Meyer H, Greiser-Wilke I, Sprague LD, Neubauer H. 2006. Detection of Burkholderia cepacia DNA from artificially infected EDTA-blood and lung tissue comparing different DNA isolation methods. J Vet Med B Infect Dis Vet Public Health 53:281–285.
    277.
    Knappik M, Dance DA, Rattanavong S, Pierret A, Ribolzi O, Davong V, Silisouk J, Vongsouvath M, Newton PN, Dittrich S. 2015. Evaluation of molecular methods to improve the detection of Burkholderia pseudomallei in soil and water samples from Laos. Appl Environ Microbiol 81:3722–3727.
    278.
    Michel PA, Lascols C, Gee JE, Weigel LM, Sue D. 2017. Rapid filter-based detection and culture of Burkholderia pseudomallei from small volumes of urine. J Clin Microbiol 55:2698–2707.
    279.
    Currie BJ. 2015. Melioidosis: evolving concepts in epidemiology, pathogenesis, and treatment. Semin Respir Crit Care Med 36:111–125.
    280.
    CLSI. 2010. Performance standards for antimicrobial susceptibility testing; twentieth informational supplement M100-S20. CLSI, Wayne, PA.
    281.
    Inglis TJ, Rodrigues F, Rigby P, Norton R, Currie BJ. 2004. Comparison of the susceptibilities of Burkholderia pseudomallei to meropenem and ceftazidime by conventional and intracellular methods. Antimicrob Agents Chemother 48:2999–3005.
    282.
    Dance DA, Davong V, Soeng S, Phetsouvanh R, Newton PN, Turner P. 2014. Trimethoprim/sulfamethoxazole resistance in Burkholderia pseudomallei. Int J Antimicrob Agents 44:368–369.
    283.
    Wiersinga WJ, Currie BJ, Peacock SJ. 2012. Melioidosis. N Engl J Med 367:1035–1044.
    284.
    Jenney AWJ, Lum G, Fisher DA, Currie BJ. 2001. Antibiotic susceptibility of Burkholderia pseudomallei from tropical northern Australia and implications for therapy of melioidosis. Int J Antimicrob Agents 17:109–113.
    285.
    Dance DA, Wuthiekanun V, Chaowagul W, White NJ. 1989. The antimicrobial susceptibility of Pseudomonas pseudomallei. Emergence of resistance in vitro and during treatment. J Antimicrob Chemother 24:295–309.
    286.
    Podnecky NL, Rhodes KA, Schweizer HP. 2015. Efflux pump-mediated drug resistance in Burkholderia. Front Microbiol 6:305.
    287.
    Rhodes KA, Schweizer HP. 2016. Antibiotic resistance in Burkholderia species. Drug Resist Updat 28:82–90.
    288.
    Burtnick MN, Woods DE. 1999. Isolation of polymyxin B-susceptible mutants of Burkholderia pseudomallei and molecular characterization of genetic loci involved in polymyxin B resistance. Antimicrob Agents Chemother 43:2648–2656.
    289.
    Chan YY, Ong YM, Chua KL. 2007. Synergistic interaction between phenothiazines and antimicrobial agents against Burkholderia pseudomallei. Antimicrob Agents Chemother 51:623–630.
    290.
    Loutet SA, Valvano MA. 2011. Extreme antimicrobial peptide and polymyxin B resistance in the genus Burkholderia. Front Microbiol 2:159.
    291.
    Dutta S, Haq S, Hasan MR, Haq JA. 2017. Antimicrobial susceptibility pattern of clinical isolates of Burkholderia pseudomallei in Bangladesh. BMC Res Notes 10:299.
    292.
    Khosravi Y, Vellasamy KM, Mariappan V, Ng S-L, Vadivelu J. 2014. Antimicrobial susceptibility and genetic characterisation of Burkholderia pseudomallei isolated from Malaysian patients. Sci World J 2014:9.
    293.
    Wuthiekanun V, Amornchai P, Saiprom N, Chantratita N, Chierakul W, Koh GC, Chaowagul W, Day NP, Limmathurotsakul D, Peacock SJ. 2011. Survey of antimicrobial resistance in clinical Burkholderia pseudomallei isolates over two decades in Northeast Thailand. Antimicrob Agents Chemother 55:5388–5391.
    294.
    Rholl DA, Papp-Wallace KM, Tomaras AP, Vasil ML, Bonomo RA, Schweizer HP. 2011. Molecular investigations of PenA-mediated beta-lactam resistance in Burkholderia pseudomallei. Front Microbiol 2:139.
    295.
    Bugrysheva JV, Sue D, Gee JE, Elrod MG, Hoffmaster AR, Randall LB, Chirakul S, Tuanyok A, Schweizer HP, Weigel LM. 2017. Antibiotic resistance markers in Burkholderia pseudomallei strain Bp1651 identified by genome sequence analysis. Antimicrob Agents Chemother 61:e00010-17.
    296.
    Chirakul S, Somprasong N, Norris MH, Wuthiekanun V, Chantratita N, Tuanyok A, Schweizer HP. 2019. Burkholderia pseudomallei acquired ceftazidime resistance due to gene duplication and amplification. Int J Antimicrob Agents 53:582–588.
    297.
    Chantratita N, Rholl DA, Sim B, Wuthiekanun V, Limmathurotsakul D, Amornchai P, Thanwisai A, Chua HH, Ooi WF, Holden MT, Day NP, Tan P, Schweizer HP, Peacock SJ. 2011. Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in Burkholderia pseudomallei. Proc Natl Acad Sci U S A 108:17165–17170.
    298.
    Crowe A, McMahon N, Currie BJ, Baird RW. 2014. Current antimicrobial susceptibility of first-episode melioidosis Burkholderia pseudomallei isolates from the Northern Territory, Australia. Int J Antimicrob Agents 44:160–162.
    299.
    Shih HI, Chuang YC, Cheung BMH, Yan JJ, Chang CM, Chang K, Lee NY, Lee HC, Wu CJ, Chen PL, Lee CC, Wang LR, Ko NY, Ko WC. 2008. Sporadic and outbreak cases of melioidosis in southern Taiwan: clinical features and antimicrobial susceptibility. Infection 37:9.
    300.
    Tan AL, Tan M-L. 2008. Melioidosis: antibiogram of cases in Singapore 1987–2007. Trans R Soc Trop Med Hyg 102:S101–S102.
    301.
    Sarovich DS, Price EP, Von Schulze AT, Cook JM, Mayo M, Watson LM, Richardson L, Seymour ML, Tuanyok A, Engelthaler DM, Pearson T, Peacock SJ, Currie BJ, Keim P, Wagner DM. 2012. Characterization of ceftazidime resistance mechanisms in clinical isolates of Burkholderia pseudomallei from Australia. PLoS One 7:e30789.
    302.
    O’Callaghan CH, Acred P, Harper PB, Ryan DM, Kirby SM, Harding SM. 1980. GR 20263, a new broad-spectrum cephalosporin with anti-pseudomonal activity. Antimicrob Agents Chemother 17:876.
    303.
    Sarovich DS, Price EP, Limmathurotsakul D, Cook JM, Von Schulze AT, Wolken SR, Keim P, Peacock SJ, Pearson T. 2012. Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection. Infect Drug Resist 5:129–132.
    304.
    Saiprom N, Amornchai P, Wuthiekanun V, Day NPJ, Limmathurotsakul D, Peacock SJ, Chantratita N. 2015. Trimethoprim/sulfamethoxazole resistance in clinical isolates of Burkholderia pseudomallei from Thailand. Int J Antimicrob Agents 45:557–559.
    305.
    Wuthiekanun V, Cheng AC, Chierakul W, Amornchai P, Limmathurotsakul D, Chaowagul W, Simpson AJ, Short JM, Wongsuvan G, Maharjan B, White NJ, Peacock SJ. 2005. Trimethoprim/sulfamethoxazole resistance in clinical isolates of Burkholderia pseudomallei. J Antimicrob Chemother 55:1029–1031.
    306.
    Piliouras P, Ulett GC, Ashhurst-Smith C, Hirst RG, Norton RE. 2002. A comparison of antibiotic susceptibility testing methods for cotrimoxazole with Burkholderia pseudomallei. Int J Antimicrob Agents 19:427–429.
    307.
    Ahmad N, Hashim R, Mohd Noor A. 2013. The in vitro antibiotic susceptibility of Malaysian isolates of Burkholderia pseudomallei. Int J Microbiol 2013:121845.
    308.
    Bandeira TDJPG, Brilhante RSN, Rocha MFG, Moreira CA, Cordeiro RdA, Ribeiro JF, Castelo-Branco DDSCM, Sidrim JJC. 2013. In vitro antimicrobial susceptibility of clinical and environmental strains of Burkholderia pseudomallei from Brazil. Int J Antimicrob Agents 42:375–377.
    309.
    Sarovich DS, Webb JR, Pitman MC, Viberg LT, Mayo M, Baird RW, Robson JM, Currie BJ, Price EP. 2018. Raising the stakes: loss of efflux pump regulation decreases meropenem susceptibility in Burkholderia pseudomallei. Clin Infect Dis 67:243–250.
    310.
    Viktorov DV, Zakharova IB, Podshivalova MV, Kalinkina EV, Merinova OA, Ageeva NP, Antonov VA, Merinova LK, Alekseev VV. 2008. High-level resistance to fluoroquinolones and cephalosporins in Burkholderia pseudomallei and closely related species. Trans R Soc Trop Med Hyg 102(Suppl 1):S103–S110.
    311.
    Chan YY, Tan TM, Ong YM, Chua KL. 2004. BpeAB-OprB, a multidrug efflux pump in Burkholderia pseudomallei. Antimicrob Agents Chemother 48:1128–1135.
    312.
    Moore RA, DeShazer D, Reckseidler S, Weissman A, Woods DE. 1999. Efflux-mediated aminoglycoside and macrolide resistance in Burkholderia pseudomallei. Antimicrob Agents Chemother 43:465–470.
    313.
    Trunck LA, Propst KL, Wuthiekanun V, Tuanyok A, Beckstrom-Sternberg SM, Beckstrom-Sternberg JS, Peacock SJ, Keim P, Dow SW, Schweizer HP. 2009. Molecular basis of rare aminoglycoside susceptibility and pathogenesis of Burkholderia pseudomallei clinical isolates from Thailand. PLoS Negl Trop Dis 3:e519.
    314.
    Sawasdidoln C, Taweechaisupapong S, Sermswan RW, Tattawasart U, Tungpradabkul S, Wongratanacheewin S. 2010. Growing Burkholderia pseudomallei in biofilm stimulating conditions significantly induces antimicrobial resistance. PLoS One 5:e9196.
    315.
    Pibalpakdee P, Wongratanacheewin S, Taweechaisupapong S, Niumsup PR. 2012. Diffusion and activity of antibiotics against Burkholderia pseudomallei biofilms. Int J Antimicrob Agents 39:356–359.
    316.
    Anuntagool N, Wuthiekanun V, White NJ, Currie BJ, Sermswan RW, Wongratanacheewin S, Taweechaisupapong S, Chaiyaroj SC, Sirisinha S. 2006. Lipopolysaccharide heterogeneity among Burkholderia pseudomallei from different geographic and clinical origins. Am J Trop Med Hyg 74:348–352.
    317.
    Hamad MA, Austin CR, Stewart AL, Higgins M, Vázquez-Torres A, Voskuil MI. 2011. Adaptation and antibiotic tolerance of anaerobic Burkholderia pseudomallei. Antimicrob Agents Chemother 55:3313–3323.
    318.
    Thomas AD, Forbes-Faulkner J, Parker M. 1979. Isolation of Pseudomonas pseudomallei from clay layers at defined depths. Am J Epidemiol 110:515–521.
    319.
    Trung TT, Hetzer A, Topfstedt E, Gohler A, Limmathurotsakul D, Wuthiekanun V, Peacock SJ, Steinmetz I. 2011. Improved culture-based detection and quantification of Burkholderia pseudomallei from soil. Trans R Soc Trop Med Hyg 105:346–351.
    320.
    Thomas AD, Forbes-Faulkner JC. 1981. Persistence of Pseudomonas pseudomallei in soil. Aust Vet J 57:535–536.
    321.
    Wuthiekanun V, Smith MD, Dance DA, White NJ. 1995. Isolation of Pseudomonas pseudomallei from soil in north-eastern Thailand. Trans R Soc Trop Med Hyg 89:41–43.
    322.
    Kaestli M, Harrington G, Mayo M, Chatfield MD, Harrington I, Hill A, Munksgaard N, Gibb K, Currie BJ. 2015. What drives the occurrence of the melioidosis bacterium Burkholderia pseudomallei in domestic gardens? PLoS Negl Trop Dis 9:e0003635.
    323.
    Kaestli M, Mayo M, Harrington G, Ward L, Watt F, Hill JV, Cheng AC, Currie BJ. 2009. Landscape changes influence the occurrence of the melioidosis bacterium Burkholderia pseudomallei in soil in northern Australia. PLoS Negl Trop Dis 3:e364.
    324.
    Mayo M, Kaesti M, Harrington G, Cheng AC, Ward L, Karp D, Jolly P, Godoy D, Spratt BG, Currie BJ. 2011. Burkholderia pseudomallei in unchlorinated domestic bore water, tropical northern Australia. Emerg Infect Dis 17:1283–1285.
    325.
    Ellison DW, Baker HJ, Mariappan M. 1969. Melioidosis in Malaysia. I. A method for isolation of Pseudomonas pseudomallei from soil and surface water. Am J Trop Med Hyg 18:694–697.
    326.
    Zanetti F, De Luca G, Stampi S. 2000. Recovery of Burkholderia pseudomallei and B. cepacia from drinking water. Int J Food Microbiol 59:67–72.
    327.
    Trung TT, Hetzer A, Göhler A, Topfstedt E, Wuthiekanun V, Limmathurotsakul D, Peacock SJ, Steinmetz I. 2011. Highly sensitive direct detection and quantification of Burkholderia pseudomallei bacteria in environmental soil samples by using real-time PCR. Appl Environ Microbiol 77:6486–6494.
    328.
    Kaestli M, Mayo M, Harrington G, Watt F, Hill J, Gal D, Currie BJ. 2007. Sensitive and specific molecular detection of Burkholderia pseudomallei, the causative agent of melioidosis, in the soil of tropical northern Australia. Appl Environ Microbiol 73:6891–6897.
    329.
    Antonov VA, Tkachenko GA, Altukhova VV, Savchenko SS, Zinchenko OV, Viktorov DV, Zamaraev VS, Ilyukhin VI, Alekseev VV. 2008. Molecular identification and typing of Burkholderia pseudomallei and Burkholderia mallei: when is enough enough? Trans R Soc Trop Med Hyg 102:S134–S139.
    330.
    Zulkefli NJ, Mariappan V, Vellasamy KM, Chong CW, Thong KL, Ponnampalavanar S, Vadivelu J, Teh CSJ. 2016. Molecular evidence of Burkholderia pseudomallei genotypes based on geographical distribution. PeerJ 4:e1802.
    331.
    Lew AE, Desmarchelier PM. 1993. Molecular typing of Pseudomonas pseudomallei: restriction fragment length polymorphisms of rRNA genes. J Clin Microbiol 31:533–539.
    332.
    Currie B, Smith-Vaughan H, Golledge C, Buller N, Sriprakash KS, Kemp DJ. 1994. Pseudomonas pseudomallei isolates collected over 25 years from a non-tropical endemic focus show clonality on the basis of ribotyping. Epidemiol Infect 113:307–312.
    333.
    Trakulsomboon S, Dance DAB, Smith MD, White NJ, Pitt TL. 1997. Ribotype differences between clinical and environmental isolates of Burkholderia pseudomallei. J Med Microbiol 46:565–570.
    334.
    Haase A, Smith-Vaughan H, Melder A, Wood Y, Janmaat A, Gilfedder J, Kemp D, Currie B. 1995. Subdivision of Burkholderia pseudomallei ribotypes into multiple types by random amplified polymorphic DNA analysis provides new insights into epidemiology. J Clin Microbiol 33:1687–1690.
    335.
    Pitt TL, Trakulsomboon S, Dance DAB. 2000. Molecular phylogeny of Burkholderia pseudomallei. Acta Trop 74:181–185.
    336.
    Vadivelu J, Puthucheary SD, Mifsud A, Drasar BS, Dance DAB, Pitt TL. 1997. Ribotyping and DNA macrorestriction analysis of isolates of Burkholderia pseudomallei from cases of melioidosis in Malaysia. Trans R Soc Trop Med Hyg 91:358–360.
    337.
    Inglis TJ, Garrow SC, Adams C, Henderson M, Mayo M, Currie BJ. 1999. Acute melioidosis outbreak in Western Australia. Epidemiol Infect 123:437–443.
    338.
    Inglis TJ, O’Reilly L, Foster N, Clair A, Sampson J. 2002. Comparison of rapid, automated ribotyping and DNA macrorestriction analysis of Burkholderia pseudomallei. J Clin Microbiol 40:3198–3203.
    339.
    Godoy D, Randle G, Simpson AJ, Aanensen DM, Pitt TL, Kinoshita R, Spratt BG. 2003. Multilocus sequence typing and evolutionary relationships among the causative agents of melioidosis and glanders, Burkholderia pseudomallei and Burkholderia mallei. J Clin Microbiol 41:2068–2079.
    340.
    Nualnoi T, Norris MH, Tuanyok A, Brett PJ, Burtnick MN, Keim PS, Settles EW, Allender CJ, AuCoin DP. 2017. Development of immunoassays for Burkholderia pseudomallei typical and atypical lipopolysaccharide strain typing. Am J Trop Med Hyg 96:358–367.
    341.
    Tuanyok A, Stone JK, Mayo M, Kaestli M, Gruendike J, Georgia S, Warrington S, Mullins T, Allender CJ, Wagner DM, Chantratita N, Peacock SJ, Currie BJ, Keim P. 2012. The genetic and molecular basis of O-antigenic diversity in Burkholderia pseudomallei lipopolysaccharide. PLoS Negl Trop Dis 6:e1453.
    342.
    Stone JK, Mayo M, Grasso SA, Ginther JL, Warrington SD, Allender CJ, Doyle A, Georgia S, Kaestli M, Broomall SM, Karavis MA, Insalaco JM, Hubbard KS, McNew LA, Gibbons HS, Currie BJ, Keim P, Tuanyok A. 2012. Detection of Burkholderia pseudomallei O-antigen serotypes in near-neighbor species. BMC Microbiol 12:250.
    343.
    Webb JR, Sarovich DS, Price EP, Ward LM, Mayo M, Currie BJ. 2019. Burkholderia pseudomallei lipopolysaccharide genotype does not correlate with severity or outcome in melioidosis: host risk factors remain the critical determinant. Open Forum Infect Dis 6:ofz091.
    344.
    Webb JR, Rachlin A, Rigas V, Sarovich DS, Price EP, Kaestli M, Ward LM, Mayo M, Currie BJ. 2019. Tracing the environmental footprint of the Burkholderia pseudomallei lipopolysaccharide genotypes in the tropical “Top End” of the Northern Territory, Australia. bioRxiv doi:
    345.
    Maiden MC, Bygraves JA, Feil E, Morelli G, Russell JE, Urwin R, Zhang Q, Zhou J, Zurth K, Caugant DA, Feavers IM, Achtman M, Spratt BG. 1998. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A 95:3140–3145.
    346.
    Price EP, MacHunter B, Spratt BG, Wagner DM, Currie BJ, Sarovich DS. 2016. Improved multilocus sequence typing of Burkholderia pseudomallei and closely related species. J Med Microbiol 65:992–997.
    347.
    De Smet B, Sarovich DS, Price EP, Mayo M, Theobald V, Kham C, Heng S, Thong P, Holden MTG, Parkhill J, Peacock SJ, Spratt BG, Jacobs JA, Vandamme P, Currie BJ. 2015. Whole-genome sequencing confirms that Burkholderia pseudomallei multilocus sequence types common to both Cambodia and Australia are due to homoplasy. J Clin Microbiol 53:323–326.
    348.
    Turner KME, Hanage WP, Fraser C, Connor TR, Spratt BG. 2007. Assessing the reliability of eBURST using simulated populations with known ancestry. BMC Microbiol 7:30.
    349.
    Liguori AP, Warrington SD, Ginther JL, Pearson T, Bowers J, Glass MB, Mayo M, Wuthiekanun V, Engelthaler D, Peacock SJ, Currie BJ, Wagner DM, Keim P, Tuanyok A. 2011. Diversity of 16S-23S rDNA internal transcribed spacer (ITS) reveals phylogenetic relationships in Burkholderia pseudomallei and its near-neighbors. PLoS One 6:e29323.
    350.
    Gee JE, Allender CJ, Tuanyok A, Elrod MG, Hoffmaster AR. 2014. Burkholderia pseudomallei type G in Western Hemisphere. Emerg Infect Dis 20:682–684.
    351.
    Lewis ERG, Kilgore PB, Mott TM, Pradenas GA, Torres AG. 2017. Comparing in vitro and in vivo virulence phenotypes of Burkholderia pseudomallei type G strains. PLoS One 12:e0175983.
    352.
    Nandi T, Tan P. 2012. The Burkholderia pseudomallei genome—an emerging model for microbial complexity and pathogen virulence, p 68–81. In Ketheesan N (ed), Melioidosis: a century of observation and research. Elsevier, Amsterdam, the Netherlands.
    353.
    Holden MT, Titball RW, Peacock SJ, Cerdeno-Tarraga AM, Atkins T, Crossman LC, Pitt T, Churcher C, Mungall K, Bentley SD, Sebaihia M, Thomson NR, Bason N, Beacham IR, Brooks K, Brown KA, Brown NF, Challis GL, Cherevach I, Chillingworth T, Cronin A, Crossett B, Davis P, DeShazer D, Feltwell T, Fraser A, Hance Z, Hauser H, Holroyd S, Jagels K, Keith KE, Maddison M, Moule S, Price C, Quail MA, Rabbinowitsch E, Rutherford K, Sanders M, Simmonds M, Songsivilai S, Stevens K, Tumapa S, Vesaratchavest M, Whitehead S, Yeats C, Barrell BG, Oyston PC, Parkhill J. 2004. Genomic plasticity of the causative agent of melioidosis, Burkholderia pseudomallei. Proc Natl Acad Sci U S A 101:14240–14245.
    354.
    Spring-Pearson SM, Stone JK, Doyle A, Allender CJ, Okinaka RT, Mayo M, Broomall SM, Hill JM, Karavis MA, Hubbard KS, Insalaco JM, McNew LA, Rosenzweig CN, Gibbons HS, Currie BJ, Wagner DM, Keim P, Tuanyok A. 2015. Pangenome analysis of Burkholderia pseudomallei: genome evolution preserves gene order despite high recombination rates. PLoS One 10:e0140274.
    355.
    Sim SH, Yu Y, Lin CH, Karuturi RKM, Wuthiekanun V, Tuanyok A, Chua HH, Ong C, Paramalingam SS, Tan G, Tang L, Lau G, Ooi EE, Woods D, Feil E, Peacock SJ, Tan P. 2008. The core and accessory genomes of Burkholderia pseudomallei: implications for human melioidosis. PLoS Pathog 4:e1000178.
    356.
    Tuanyok A. 2012. Genomic islands in Burkholderia pseudomallei, p 82–86. In Ketheesan N (ed), Melioidosis: a century of observation and research. Elsevier, Amsterdam, the Netherlands.
    357.
    Tuanyok A, Leadem BR, Auerbach RK, Beckstrom-Sternberg SM, Beckstrom-Sternberg JS, Mayo M, Wuthiekanun V, Brettin TS, Nierman WC, Peacock SJ, Currie BJ, Wagner DM, Keim P. 2008. Genomic islands from five strains of Burkholderia pseudomallei. BMC Genom 9:566.
    358.
    Duangsonk K, Gal D, Mayo M, Hart CA, Currie BJ, Winstanley C. 2006. Use of a variable amplicon typing scheme reveals considerable variation in the accessory genomes of isolates of Burkholderia pseudomallei. J Clin Microbiol 44:1323–1334.
    359.
    Chapple SNJ, Sarovich DS, Holden MTG, Peacock SJ, Buller N, Golledge C, Mayo M, Currie BJ, Price EP. 2016. Whole-genome sequencing of a quarter-century melioidosis outbreak in temperate Australia uncovers a region of low-prevalence endemicity. Microb Genom 2:e000067.
    360.
    Limmathurotsakul D, Holden MTG, Coupland P, Price EP, Chantratita N, Wuthiekanun V, Amornchai P, Parkhill J, Peacock SJ. 2014. Microevolution of Burkholderia pseudomallei during an acute infection. J Clin Microbiol 52:3418–3421.
    361.
    Robertson J, Levy A, Sagripanti J-L, Inglis TJJ. 2010. The survival of Burkholderia pseudomallei in liquid media. Am J Trop Med Hyg 82:88–94.
    362.
    Gal D, Mayo M, Smith-Vaughan H, Dasari P, McKinnon M, Jacups SP, Urquhart AI, Hassell M, Currie BJ. 2004. Contamination of hand wash detergent linked to occupationally acquired melioidosis. Am J Trop Med Hyg 71:360–362.
    363.
    Ooi S-K, Lim T-Y, Lee S-H, Nathan S. 2012. Burkholderia pseudomallei kills Caenorhabditis elegans through virulence mechanisms distinct from intestinal lumen colonization. Virulence 3:485–496.
    364.
    Soffler C, Bosco-Lauth AM, Aboellail TA, Marolf AJ, Bowen RA. 2014. Pathogenesis of percutaneous infection of goats with Burkholderia pseudomallei: clinical, pathologic, and immunological responses in chronic melioidosis. Int J Exp Pathol 95:101–119.
    365.
    Warawa JM. 2010. Evaluation of surrogate animal models of melioidosis. Front Microbiol 1:141.
    366.
    Leakey AK, Ulett GC, Hirst RG. 1998. BALB/c and C57Bl/6 mice infected with virulent Burkholderia pseudomallei provide contrasting animal models for the acute and chronic forms of human melioidosis. Microb Pathog 24:269–275.
    367.
    Liu B, Koo GC, Yap EH, Chua KL, Gan YH. 2002. Model of differential susceptibility to mucosal Burkholderia pseudomallei infection. Infect Immun 70:504–511.
    368.
    Tan GY, Liu Y, Sivalingam SP, Sim SH, Wang D, Paucod JC, Gauthier Y, Ooi EE. 2008. Burkholderia pseudomallei aerosol infection results in differential inflammatory responses in BALB/c and C57Bl/6 mice. J Med Microbiol 57:508–515.
    369.
    Galyov EE, Brett PJ, DeShazer D. 2010. Molecular insights into Burkholderia pseudomallei and Burkholderia mallei pathogenesis. Annu Rev Microbiol 64:495.
    370.
    Lazar Adler NR, Govan B, Cullinane M, Harper M, Adler B, Boyce JD. 2009. The molecular and cellular basis of pathogenesis in melioidosis: how does Burkholderia pseudomallei cause disease? FEMS Microbiol Rev 33:1079.
    371.
    Inglis TJ, Robertson T, Woods DE, Dutton N, Chang BJ. 2003. Flagellum-mediated adhesion by Burkholderia pseudomallei precedes invasion of Acanthamoeba astronyxis. Infect Immun 71:2280–2282.
    372.
    Essex-Lopresti AE, Boddey JA, Thomas R, Smith MP, Hartley MG, Atkins T, Brown NF, Tsang CH, Ian RAP, Hill J, Beacham IR, Titball RW. 2005. A type IV pilin, PilA, contributes to adherence of Burkholderia pseudomallei and virulence in vivo. Infect Immun 73:1260–1264.
    373.
    Ahmed K, Enciso HD, Masaki H, Tao M, Omori A, Tharavichikul P, Nagatake T. 1999. Attachment of Burkholderia pseudomallei to pharyngeal epithelial cells: a highly pathogenic bacteria with low attachment ability. Am J Trop Med Hyg 60:90–93.
    374.
    Gori AH, Ahmed K, Martinez G, Masaki H, Watanabe K, Nagatake T. 1999. Mediation of attachment of Burkholderia pseudomallei to human pharyngeal epithelial cells by the asialoganglioside GM1-GM2 receptor complex. Am J Trop Med Hyg 61:473–475.
    375.
    Jones AL, Beveridge TJ, Woods DE. 1996. Intracellular survival of Burkholderia pseudomallei. Infect Immun 64:782–790.
    376.
    Allwood EM, Devenish RJ, Prescott M, Adler B, Boyce JD. 2011. Strategies for intracellular survival of Burkholderia pseudomallei. Front Microbiol 2:170.
    377.
    Chen Y, Schröder I, French CT, Jaroszewicz A, Yee XJ, Teh B-E, Toesca IJ, Miller JF, Gan Y-H. 2014. Characterization and analysis of the Burkholderia pseudomallei BsaN virulence regulon. BMC Microbiol 14:206.
    378.
    Warawa J, Woods DE. 2005. Type III secretion system cluster 3 is required for maximal virulence of Burkholderia pseudomallei in a hamster infection model. FEMS Microbiol Lett 242:101–108.
    379.
    Schwarz S, West TE, Boyer F, Chiang W-C, Carl MA, Hood RD, Rohmer L, Tolker-Nielsen T, Skerrett SJ, Mougous JD. 2010. Burkholderia type VI secretion systems have distinct roles in eukaryotic and bacterial cell interactions. PLoS Pathog 6:e1001068.
    380.
    Sun GW, Chen Y, Liu Y, Tan GY, Ong C, Tan P, Gan YH. 2010. Identification of a regulatory cascade controlling type III secretion system 3 gene expression in Burkholderia pseudomallei. Mol Microbiol 76:677–689.
    381.
    Vander Broek CW, Stevens JM. 2017. Type III secretion in the melioidosis pathogen Burkholderia pseudomallei. Front Cell Infect Microbiol 7:255.
    382.
    Galán JE, Lara-Tejero M, Marlovits TC, Wagner S. 2014. Bacterial type III secretion systems: specialized nanomachines for protein delivery into target cells. Annu Rev Microbiol 68:415–438.
    383.
    Stevens MP, Haque A, Atkins T, Hill J, Wood MW, Easton A, Nelson M, Underwood-Fowler C, Titball RW, Bancroft GJ, Galyov EE. 2004. Attenuated virulence and protective efficacy of a Burkholderia pseudomallei bsa type III secretion mutant in murine models of melioidosis. Microbiology 150:2669–2676.
    384.
    Suparak S, Kespichayawattana W, Haque A, Easton A, Damnin S, Lertmemongkolchai G, Bancroft GJ, Korbsrisate S. 2005. Multinucleated giant cell formation and apoptosis in infected host cells is mediated by Burkholderia pseudomallei type III secretion protein BipB. J Bacteriol 187:6556–6560.
    385.
    Kang WT, Vellasamy KM, Rajamani L, Beuerman RW, Vadivelu J. 2016. Burkholderia pseudomallei type III secreted protein BipC: role in actin modulation and translocation activities required for the bacterial intracellular lifecycle. PeerJ 4:e2532.
    386.
    Kang WT, Vellasamy KM, Chua E-G, Vadivelu J. 2015. Functional characterizations of effector protein BipC, a type III secretion system protein, in Burkholderia pseudomallei pathogenesis. J Infect Dis 211:827–834.
    387.
    Stevens MP, Friebel A, Taylor LA, Wood MW, Brown PJ, Hardt W-D, Galyov EE. 2003. A Burkholderia pseudomallei type III secreted protein, BopE, facilitates bacterial invasion of epithelial cells and exhibits guanine nucleotide exchange factor activity. J Bacteriol 185:4992–4996.
    388.
    Ireland PM, Marshall L, Norville I, Sarkar-Tyson M. 2014. The serine protease inhibitor Ecotin is required for full virulence of Burkholderia pseudomallei. Microb Pathog 67-68:55–58.
    389.
    Stevens MP, Wood MW, Taylor LA, Monaghan P, Hawes P, Jones PW, Wallis TS, Galyov EE. 2002. An Inv/Mxi-Spa-like type III protein secretion system in Burkholderia pseudomallei modulates intracellular behaviour of the pathogen. Mol Microbiol 46:649–659.
    390.
    French CT, Toesca IJ, Wu T-H, Teslaa T, Beaty SM, Wong W, Liu M, Schröder I, Chiou P-Y, Teitell MA, Miller JF. 2011. Dissection of the Burkholderia intracellular life cycle using a photothermal nanoblade. Proc Natl Acad Sci U S A 108:12095–12100.
    391.
    Vadivelu J, Vellasamy KM, Thimma J, Mariappan V, Kang W-T, Choh L-C, Shankar EM, Wong KT. 2017. Survival and intra-nuclear trafficking of Burkholderia pseudomallei: strategies of evasion from immune surveillance? PLoS Negl Trop Dis 11:e0005241.
    392.
    Nathan SA, Puthucheary SD. 2005. An electronmicroscopic study of the interaction of Burkholderia pseudomallei and human macrophages. Malays J Pathol 27:3.
    393.
    Willcocks SJ, Denman CC, Atkins HS, Wren BW. 2015. Intracellular replication of the well-armed pathogen Burkholderia pseudomallei. Curr Opin Microbiol 29:94–103.
    394.
    Ekchariyawat P, Pudla S, Limposuwan K, Arjcharoen S, Sirisinha S, Utaisincharoen P. 2005. Burkholderia pseudomallei-induced expression of suppressor of cytokine signaling 3 and cytokine-inducible Src homology 2-containing protein in mouse macrophages: a possible mechanism for suppression of the response to gamma interferon stimulation. Infect Immun 73:7332–7339.
    395.
    Miyagi K, Kawakami K, Saito A. 1997. Role of reactive nitrogen and oxygen intermediates in gamma interferon-stimulated murine macrophage bactericidal activity against Burkholderia pseudomallei. Infect Immun 65:4108–4113.
    396.
    Krakauer T. 2018. Living dangerously: Burkholderia pseudomallei modulates phagocyte cell death to survive. Med Hypotheses 121:64–69.
    397.
    Kespichayawattana W, Rattanachetkul S, Wanun T, Utaisincharoen P, Sirisinha S. 2000. Burkholderia pseudomallei induces cell fusion and actin-associated membrane protrusion: a possible mechanism for cell-to-cell spreading. Infect Immun 68:5377–5384.
    398.
    Stevens JM, Galyov EE, Stevens MP. 2006. Actin-dependent movement of bacterial pathogens. Nat Rev Microbiol 4:91–101.
    399.
    Breitbach K, Rottner K, Klocke S, Rohde M, Jenzora A, Wehland J, Steinmetz I. 2003. Actin-based motility of Burkholderia pseudomallei involves the Arp 2/3 complex, but not N-WASP and Ena/VASP proteins. Cell Microbiol 5:385–393.
    400.
    Stevens MP, Stevens JM, Jeng RL, Taylor LA, Wood MW, Hawes P, Monaghan P, Welch MD, Galyov EE. 2005. Identification of a bacterial factor required for actin-based motility of Burkholderia pseudomallei. Mol Microbiol 56:40–53.
    401.
    Sarovich DS, Price EP, Webb JR, Ward LM, Voutsinos MY, Tuanyok A, Mayo M, Kaestli M, Currie BJ. 2014. Variable virulence factors in Burkholderia pseudomallei (melioidosis) associated with human disease. PLoS One 9:e91682.
    402.
    Shalom G, Shaw JG, Thomas MS. 2007. In vivo expression technology identifies a type VI secretion system locus in Burkholderia pseudomallei that is induced upon invasion of macrophages. Microbiology 153:2689–2699.
    403.
    Toesca IJ, French CT, Miller JF. 2014. The type VI secretion system spike protein VgrG5 mediates membrane fusion during intercellular spread by pseudomallei group Burkholderia species. Infect Immun 82:1436–1444.
    404.
    Schwarz S, Singh P, Robertson JD, LeRoux M, Skerrett SJ, Goodlett DR, West TE, Mougous JD. 2014. VgrG-5 is a Burkholderia type VI secretion system-exported protein required for multinucleated giant cell formation and virulence. Infect Immun 82:1445–1452.
    405.
    Lennings J, West TE, Schwarz S. 2019. The Burkholderia type VI secretion system 5: composition, regulation and role in virulence. Front Microbiol 9:3339.
    406.
    Whiteley L, Meffert T, Haug M, Weidenmaier C, Hopf V, Bitschar K, Schittek B, Kohler C, Steinmetz I, West TE, Schwarz S. 2017. Entry, intracellular survival, and multinucleated-giant-cell-forming activity of Burkholderia pseudomallei in human primary phagocytic and nonphagocytic cells. Infect Immun 85:e00468-17.
    407.
    Wong KT, Puthucheary SD, Vadivelu J. 1995. The histopathology of human melioidosis. Histopathology 26:51–55.
    408.
    Boddey JA, Day CJ, Flegg CP, Ulrich RL, Stephens SR, Beacham IR, Morrison NA, Peak IRA. 2007. The bacterial gene lfpA influences the potent induction of calcitonin receptor and osteoclast-related genes in Burkholderia pseudomallei-induced TRAP-positive multinucleated giant cells. Cell Microbiol 9:514–531.
    409.
    Burtnick MN, Brett PJ, Nair V, Warawa JM, Woods DE, Gherardini FC. 2008. Burkholderia pseudomallei type III secretion system mutants exhibit delayed vacuolar escape phenotypes in RAW 264.7 murine macrophages. Infect Immun 76:2991–3000.
    410.
    Utaisincharoen P, Arjcharoen S, Limposuwan K, Tungpradabkul S, Sirisinha S. 2006. Burkholderia pseudomallei RpoS regulates multinucleated giant cell formation and inducible nitric oxide synthase expression in mouse macrophage cell line (RAW 264.7). Microb Pathog 40:184–189.
    411.
    Gutierrez MG, Yoder-Himes DR, Warawa JM. 2015. Comprehensive identification of virulence factors required for respiratory melioidosis using Tn-seq mutagenesis. Front Cell Infect Microbiol 5:78.
    412.
    Reckseidler SL, DeShazer D, Sokol PA, Woods DE. 2001. Detection of bacterial virulence genes by subtractive hybridization: identification of capsular polysaccharide of Burkholderia pseudomallei as a major virulence determinant. Infect Immun 69:34–44.
    413.
    Reckseidler-Zenteno SL, DeVinney R, Woods DE. 2005. The capsular polysaccharide of Burkholderia pseudomallei contributes to survival in serum by reducing complement factor C3b deposition. Infect Immun 73:1106–1115.
    414.
    Atkins T, Prior R, Mack K, Russell P, Nelson M, Prior J, Ellis J, Oyston PC, Dougan G, Titball RW. 2002. Characterisation of an acapsular mutant of Burkholderia pseudomallei identified by signature tagged mutagenesis. J Med Microbiol 51:539–547.
    415.
    Puthucheary SD, Vadivelu J, Ce-Cile C, Kum-Thong W, Ismail G. 1996. Short report: electron microscopic demonstration of extracellular structure of Burkholderia pseudomallei. Am J Trop Med Hyg 54:313.
    416.
    Vorachit M, Lam K, Jayanetra P, Costerton JW. 1995. Electron microscopy study of the mode of growth of Pseudomonas pseudomallei in vitro and in vivo. Am J Trop Med Hyg 98:379.
    417.
    Sengyee S, Yoon SH, Paksanont S, Yimthin T, Wuthiekanun V, Limmathurotsakul D, West TE, Ernst RK, Chantratita N. 2018. Comprehensive analysis of clinical Burkholderia pseudomallei isolates demonstrates conservation of unique lipid A structure and TLR4-dependent innate immune activation. PLoS Negl Trop Dis 12:e0006287.
    418.
    Anuntagool N, Aramsri P, Panichakul T, Wuthiekanun VR, Kinoshita R, White NJ, Sirisinha S. 2000. Antigenic heterogeneity of lipopolysaccharide among Burkholderia pseudomallei clinical isolates Southeast Asian J Trop Med Public Health 31(Suppl 1):146.
    419.
    Norris MH, Schweizer HP, Tuanyok A. 2017. Structural diversity of Burkholderia pseudomallei lipopolysaccharides affects innate immune signaling. PLoS Negl Trop Dis 11:e0005571.
    420.
    Ulrich RL, DeShazer D, Brueggemann EE, Hines HB, Oyston PC, Jeddeloh JA. 2004. Role of quorum sensing in the pathogenicity of Burkholderia pseudomallei. J Med Microbiol 53:1053–1064.
    421.
    Valade E, Thibault FM, Gauthier YP, Palencia M, Popoff MY, Vidal DR. 2004. The PmlI-PmlR quorum-sensing system in Burkholderia pseudomallei plays a key role in virulence and modulates production of the MprA protease. J Bacteriol 186:2288–2294.
    422.
    Boyer F, Fichant G, Berthod J, Vandenbrouck Y, Attree I. 2009. Dissecting the bacterial type VI secretion system by a genome wide in silico analysis: what can be learned from available microbial genomic resources? BMC Genomics 10:104.
    423.
    Hopf V, Göhler A, Eske-Pogodda K, Bast A, Steinmetz I, Breitbach K. 2014. BPSS1504, a cluster 1 type VI secretion gene, is involved in intracellular survival and virulence of Burkholderia pseudomallei. Infect Immun 82:2006–2015.
    424.
    DeShazer D, Brett PJ, Burtnick MN, Woods DE. 1999. Molecular characterization of genetic loci required for secretion of exoproducts in Burkholderia pseudomallei. J Bacteriol 181:4661–4664.
    425.
    Gauthier YP, Thibault FM, Paucod JC, Vidal DR. 2000. Protease production by Burkholderia pseudomallei and virulence in mice. Acta Trop 74:215–220.
    426.
    Duangurai T, Indrawattana N, Pumirat P. 2018. Burkholderia pseudomallei adaptation for survival in stressful conditions. BioMed Res Int 2018:11.
    427.
    Subsin B, Thomas MS, Katzenmeier G, Shaw JG, Tungpradabkul S, Kunakorn M. 2003. Role of the stationary growth phase sigma factor RpoS of Burkholderia pseudomallei in response to physiological stress conditions. J Bacteriol 185:7008–7014.
    428.
    Korbsrisate S, Vanaporn M, Kerdsuk P, Kespichayawattana W, Vattanaviboon P, Kiatpapan P, Lertmemongkolchai G. 2005. The Burkholderia pseudomallei RpoE (AlgU) operon is involved in environmental stress tolerance and biofilm formation. FEMS Microbiol Lett 252:243–249.
    429.
    Thongboonkerd V, Vanaporn M, Songtawee N, Kanlaya R, Sinchaikul S, Chen S-T, Easton A, Chu K, Bancroft GJ, Korbsrisate S. 2007. Altered proteome in Burkholderia pseudomallei rpoE operon knockout mutant: insights into mechanisms of rpoE operon in stress tolerance, survival, and virulence. J Proteome Res 6:1334.
    430.
    Chantratita N, Wuthiekanun V, Boonbumrung K, Tiyawisutsri R, Vesaratchavest M, Limmathurotsakul D, Chierakul W, Wongratanacheewin S, Pukritiyakamee S, White NJ, Nicholas PJD, Peacock SJ. 2007. Biological relevance of colony morphology and phenotypic switching by Burkholderia pseudomallei. J Bacteriol 189:807–817.
    431.
    Proctor RA, von Eiff C, Kahl BC, Becker K, McNamara P, Herrmann M, Peters G. 2006. Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat Rev Microbiol 4:295–305.
    432.
    Häußler S, Rohde M, Steinmetz I. 1999. Highly resistant Burkholderia pseudomallei small colony variants isolated in vitro and in experimental melioidosis. Med Microbiol Immunol 188:91–97.
    433.
    Nur Siti KR, Guan CE, Nathan S, Vadivelu J. 2012. The effect of environmental conditions on biofilm formation of Burkholderia pseudomallei clinical isolates. PLoS One 7:e44104.
    434.
    Austin CR, Goodyear AW, Bartek IL, Stewart A, Sutherland MD, Silva EB, Zweifel A, Vitko NP, Tuanyok A, Highnam G, Mittelman D, Keim P, Schweizer HP, Vazquez-Torres A, Dow SW, Voskuil MI. 2015. A Burkholderia pseudomallei colony variant necessary for gastric colonization. mBio 6:e0462-14.
    435.
    Tandhavanant S, Thanwisai A, Limmathurotsakul D, Korbsrisate S, Day NP, Peacock SJ, Chantratita N. 2010. Effect of colony morphology variation of Burkholderia pseudomallei on intracellular survival and resistance to antimicrobial environments in human macrophages in vitro. BMC Microbiol 10:303.
    436.
    Al-Maleki AR, Mariappan V, Vellasamy KM, Shankar EM, Tay ST, Vadivelu J. 2014. Enhanced intracellular survival and epithelial cell adherence abilities of Burkholderia pseudomallei morphotypes are dependent on differential expression of virulence-associated proteins during mid-logarithmic growth phase. J Proteom 106:205–220.
    437.
    Tuanyok A, Auerbach RK, Brettin TS, Bruce DC, Munk AC, Detter JC, Pearson T, Hornstra H, Sermswan RW, Wuthiekanun V, Peacock SJ, Currie BJ, Keim P, Wagner DM. 2007. A horizontal gene transfer event defines two distinct groups within Burkholderia pseudomallei that have dissimilar geographic distributions. J Bacteriol 189:9044–9049.
    438.
    Challacombe JF, Stubben CJ, Klimko CP, Welkos SL, Kern SJ, Bozue JA, Worsham PL, Cote CK, Wolfe DN. 2014. Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates. PLoS One 9:e115951.
    439.
    Chirakul S, Bartpho T, Wongsurawat T, Taweechaisupapong S, Karoonutaisiri N, Talaat AM, Wongratanacheewin S, Ernst RK, Sermswan RW. 2014. Characterization of BPSS1521 (bprD), a regulator of Burkholderia pseudomallei virulence gene expression in the mouse model. PLoS One 9:e104313.
    440.
    Gan Y-H. 2005. Interaction between Burkholderia pseudomallei and the host immune response: sleeping with the enemy? J Infect Dis 192:1845–1850.
    441.
    Ulett GC, Ketheesan N, Hirst RG. 2000. Cytokine gene expression in innately susceptible BALB/c mice and relatively resistant C57BL/6 mice during infection with virulent Burkholderia pseudomallei. Infect Immun 68:2034–2042.
    442.
    Ulett GC, Ketheesan N, Hirst RG. 2000. Proinflammatory cytokine mRNA responses in experimental Burkholderia pseudomallei infection in mice. Acta Trop 74:229–234.
    443.
    Riyapa D, Buddhisa S, Korbsrisate S, Cuccui J, Wren BW, Stevens MP, Ato M, Lertmemongkolchai G. 2012. Neutrophil extracellular traps exhibit antibacterial activity against Burkholderia pseudomallei and are influenced by bacterial and host factors. Infect Immun 80:3921–3929.
    444.
    Saengmuang P, Kewcharoenwong C, Tippayawat P, Nithichanon A, Buddhisa S, Lertmemongkolchai G. 2014. Effect of host factors on neutrophil functions in response to Burkholderia pseudomallei in healthy Thai subjects. Jpn J Infect Dis 67:436–440.
    445.
    Chanchamroen S, Kewcharoenwong C, Susaengrat W, Ato M, Lertmemongkolchai G. 2009. Human polymorphonuclear neutrophil responses to Burkholderia pseudomallei in healthy and diabetic subjects. Infect Immun 77:456–463.
    446.
    Rinchai D, Riyapa D, Buddhisa S, Utispan K, Titball RW, Stevens MP, Stevens JM, Ogawa M, Tanida I, Koike M, Uchiyama Y, Ato M, Lertmemongkolchai G. 2015. Macroautophagy is essential for killing of intracellular Burkholderia pseudomallei in human neutrophils. Autophagy 11:748–755.
    447.
    Easton A, Haque A, Chu K, Lukaszewski R, Bancroft GJ. 2007. A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei. J Infect Dis 195:99–107.
    448.
    Mulye M, Bechill MP, Grose W, Ferreira VP, Lafontaine ER, Wooten RM. 2014. Delineating the importance of serum opsonins and the bacterial capsule in affecting the uptake and killing of Burkholderia pseudomallei by murine neutrophils and macrophages. PLoS Negl Trop Dis 8:e2988.
    449.
    Woodman ME, Worth RG, Wooten RM. 2012. Capsule influences the deposition of critical complement C3 levels required for the killing of Burkholderia pseudomallei via NADPH-oxidase induction by human neutrophils. PLoS One 7:e52276.
    450.
    Barnes JL, Williams NL, Ketheesan N. 2008. Susceptibility to Burkholderia pseudomallei is associated with host immune responses involving tumor necrosis factor receptor-1 (TNFR1) and TNF receptor-2 (TNFR2). FEMS Immunol Med Microbiol 52:379–388.
    451.
    Wiersinga WJ, Wieland CW, Joris JTHR, Tom van der P. 2008. MyD88 dependent signaling contributes to protective host defense against Burkholderia pseudomallei. PLoS One 3:e3494.
    452.
    Wiersinga WJ, Wieland CW, Dessing MC, Chantratita N, Cheng AC, Limmathurotsakul D, Chierakul W, Leendertse M, Florquin S, de Vos AF, White N, Dondorp AM, Day NP, Peacock SJ, van der Poll T. 2007. Toll-like receptor 2 impairs host defense in gram-negative sepsis caused by Burkholderia pseudomallei (melioidosis). PLoS Med 4:e248.
    453.
    Ho M, Schollaardt T, Smith MD, Perry MB, Brett PJ, Chaowagul W, Bryan LE. 1997. Specificity and functional activity of anti-Burkholderia pseudomallei polysaccharide antibodies. Infect Immun 65:3648–3653.
    454.
    Vasu C, Vadivelu J, Puthucheary SD. 2003. The humoral immune response in melioidosis patients during therapy. Infection 31:24–30.
    455.
    Haque A, Chu K, Easton A, Stevens MP, Galyov EE, Atkins T, Titball R, Bancroft GJ. 2006. A live experimental vaccine against Burkholderia pseudomallei elicits CD4+ T cell-mediated immunity, priming T cells specific for 2 type III secretion system proteins. J Infect Dis 194:1241–1248.
    456.
    Chierakul W, Rajanuwong A, Wuthiekanun V, Teerawattanasook N, Gasiprong M, Simpson A, Chaowagul W, White NJ. 2004. The changing pattern of bloodstream infections associated with the rise in HIV prevalence in northeastern Thailand. Trans R Soc Trop Med Hyg 98:678–686.
    457.
    Brown AE, Dance DA, Suputtamongkol Y, Chaowagul W, Kongchareon S, Webster HK, White NJ. 1991. Immune cell activation in melioidosis: increased serum levels of interferon-gamma and soluble interleukin-2 receptors without change in soluble CD8 protein. J Infect Dis 163:1145–1148.
    458.
    Lauw FN, Simpson AJ, Prins JM, Smith MD, Kurimoto M, van Deventer SJ, Speelman P, Chaowagul W, White NJ, van der Poll T. 1999. Elevated plasma concentrations of interferon (IFN)-gamma and the IFN-gamma-inducing cytokines interleukin (IL)-18, IL-12, and IL-15 in severe melioidosis. J Infect Dis 180:1878–1885.
    459.
    Kessler B, Rinchai D, Kewcharoenwong C, Nithichanon A, Biggart R, Hawrylowicz CM, Bancroft GJ, Lertmemongkolchai G. 2017. Interleukin 10 inhibits pro-inflammatory cytokine responses and killing of Burkholderia pseudomallei. Sci Rep 7:42791.
    460.
    Ulett GC, Ketheesan N, Clair TW, McElnea CL, Barnes JL, Hirst RG. 2002. Analogous cytokine responses to Burkholderia pseudomallei strains contrasting in virulence correlate with partial cross-protection in immunized mice. Infect Immun 70:3953–3958.
    461.
    Lauw FN, Simpson AJ, Prins JM, van Deventer SJ, Chaowagul W, White NJ, van der Poll T. 2000. The CXC chemokines gamma interferon (IFN-gamma)-inducible protein 10 and monokine induced by IFN-gamma are released during severe melioidosis. Infect Immun 68:3888–3893.
    462.
    Santanirand P, Harley VS, Dance DAB, Drasar BS, Bancroft GJ. 1999. Obligatory role of Gamma interferon for host survival in a murine model of infection with Burkholderia pseudomallei. Infect Immun 67:3593–3600.
    463.
    Puthucheary SD, Nathan SA. 2006. Comparison by electron microscopy of intracellular events and survival of Burkholderia pseudomallei in monocytes from normal subjects and patients with melioidosis. Singapore Med J 47:697.
    464.
    Cheng AC, Wuthiekanun V, Limmathurotsakul D, Chierakul W, Peacock SJ. 2008. Intensity of exposure and incidence of melioidosis in Thai children. Trans R Soc Trop Med Hyg 102(Suppl 1):S37–S39.
    465.
    Ngauy V, Lemeshev Y, Sadkowski L, Crawford G. 2005. Cutaneous melioidosis in a man who was taken as a prisoner of war by the Japanese during World War II. J Clin Microbiol 43:970–972.
    466.
    Koponen MA, Zlock D, Palmer DL, Merlin TL. 1991. Melioidosis. Forgotten, but not gone! Arch Intern Med 151:605–608.
    467.
    Currie BJ, Fisher DA, Anstey NM, Jacups SP. 2000. Melioidosis: acute and chronic disease, relapse and re-activation. Trans R Soc Trop Med Hyg 94:301–304.
    468.
    Chodimella U, Hoppes WL, Whalen S, Ognibene AJ, Rutecki GW. 1997. Septicemia and suppuration in a Vietnam veteran. Hosp Pract 32:219–221.
    469.
    Stewart JD, Smith S, Hanson J. 2017. Melioidosis in Far North Queensland is not correlated with severe weather events. Med J Aust 207:394.
    470.
    Burivong W, Wu X, Saenkote W, Stern EJ. 2012. Thoracic radiologic manifestations of melioidosis. Curr Probl Diagn Radiol 41:199–209.
    471.
    Kozlowska J, Smith S, Roberts J, Pridgeon S, Hanson J. 2018. Prostatic abscess due to Burkholderia pseudomallei: facilitating diagnosis to optimize management. Am J Trop Med Hyg 98:227–230.
    472.
    Morse LP, Morse LP, Moller C-CB, Harvey E, Ward L. 2009. Prostatic abscess due to Burkholderia pseudomallei: 81 cases from a 19-year prospective melioidosis study. J Urol 182:542–547.
    473.
    Waiwarawooth J, Jutiworakul K, Joraka W. 2008. Epidemiology and clinical outcome of melioidosis at Chonburi Hospital, Thailand. J Infect Dis Antimicrob Agents 25:1–11.
    474.
    Fertitta L, Monsel G, Torresi J, Caumes E. 2019. Cutaneous melioidosis: a review of the literature. Int J Dermatol 58:221–227.
    475.
    McLeod C, Morris PS, Bauert PA, Kilburn CJ, Ward LM, Baird RW, Currie BJ. 2015. Clinical presentation and medical management of melioidosis in children: a 24-year prospective study in the Northern Territory of Australia and review of the literature. Clin Infect Dis 60:21–26.
    476.
    Dance DA, Davis TM, Wattanagoon Y, Chaowagul W, Saiphan P, Looareesuwan S, Wuthiekanun V, White NJ. 1989. Acute suppurative parotitis caused by Pseudomonas pseudomallei in children. J Infect Dis 159:654–660.
    477.
    Lumbiganon P, Viengnondha S. 1995. Clinical manifestations of melioidosis in children. Pediatr Infect Dis J 14:136–139.
    478.
    Clark B, Merritt A, Inglis T, Manning L. 2018. Clinical features and outcome of patients with cutaneous melioidosis during a nosocomial outbreak in a temperate region of Australia. Intern Med J 48:461–465.
    479.
    Sookpranee M, Lumbiganon P, Puapermpoonsiri S, Tattawasatra A, Nopwinyoovongs J. 1989. Contamination of Savlon solution with Pseudomonas pseudomallei at Srinagarind Hospital, p 211–213. In Punyagupta S, Sirisanthana T, Stapatayavong B (ed), Melioidosis. Bangkok Medical Publisher, Bangkok, Thailand.
    480.
    Deuble M, Aquilina C, Norton R. 2013. Neurologic melioidosis. Am J Trop Med Hyg 89:535–539.
    481.
    Limmathurotsakul D, Chaowagul W, Wongsrikaew P, Narmwong A, Day NP, Peacock SJ. 2007. Variable presentation of neurological melioidosis in Northeast Thailand. Am J Trop Med Hyg 77:118–120.
    482.
    Punyagupta S. 1989. Review of 686 cases and presentation of a new clinical classification, p 217–229. In Punyagupta S, Sirisanthana T, Stapatayavong B (ed), Melioidosis. Bangkok Medical Publisher, Bangkok, Thailand.
    483.
    Wongwandee M, Linasmita P. 2019. Central nervous system melioidosis: a systematic review of individual participant data of case reports and case series. PLoS Negl Trop Dis 13:e0007320.
    484.
    Chadwick DR, Chadwick DR, Ang B, Sitoh YY, Lee CC. 2002. Cerebral melioidosis in Singapore: a review of five cases. Trans R Soc Trop Med Hyg 96:72–76.
    485.
    Shetty RP, Mathew M, Smith J, Morse LP, Mehta JA, Currie BJ. 2015. Management of melioidosis osteomyelitis and septic arthritis. Bone Joint J 97-b:277–282.
    486.
    Teparrukkul P, Nilsakul J, Dunachie S, Limmathurotsakul D. 2017. Clinical epidemiology of septic arthritis caused by Burkholderia pseudomallei and other bacterial pathogens in northeast Thailand. Am J Trop Med Hyg 97:1695–1701.
    487.
    Teparrakkul P, Tsai JJ, Chierakul W, Gerstenmaier JF, Wacharaprechasgu T, Piyaphanee W, Limmathurotsakul D, Chaowagul W, Day NP, Peacock SJ. 2008. Rheumatological manifestations in patients with melioidosis. Southeast Asian J Trop Med Public Health 39:649–655.
    488.
    Muttarak M, Peh WC, Euathrongchit J, Lin SE, Tan AG, Lerttumnongtum P, Sivasomboon C. 2009. Spectrum of imaging findings in melioidosis. Br J Radiol 82:514–21.
    489.
    Reechaipichitkul W. 2004. Clinical manifestation of pulmonary melioidosis in adults. Southeast Asian J Trop Med Public Health 35:664–669.
    490.
    Lim KS, Chong VH. 2010. Radiological manifestations of melioidosis. Clin Radiol 65:66–72.
    491.
    Dhiensiri T, Puapairoj S, Susaengrat W. 1988. Pulmonary melioidosis: clinical-radiologic correlation in 183 cases in northeastern Thailand. Radiology 166:711–715.
    492.
    Wibulpolprasert B, Dhiensiri T. 1999. Visceral organ abscesses in melioidosis: sonographic findings. J Clin Ultrasound 27:29–34.
    493.
    Vatcharapreechasakul T, Suputtamongkol Y, Dance DA, Chaowagul W, White NJ. 1992. Pseudomonas pseudomallei liver abscesses: a clinical, laboratory, and ultrasonographic study. Clin Infect Dis 14:412–417.
    494.
    Khiangte HL, Vimala LR, Eapen A, Veeraraghavan B, Karuppusami R, Gibikote S. 2018. A retrospective case-control study to evaluate the diagnostic accuracy of honeycomb sign in melioid liver abscess. Am J Trop Med Hyg 99:852–857.
    495.
    Currie BJ, Fisher DA, Howard DM, Burrow JN. 2000. Neurological melioidosis. Acta Trop 74:145–151.
    496.
    Hsu CC-T, Singh D, Kwan G, Deuble M, Aquilina C, Korah I, Norton R. 2016. Neuromelioidosis: craniospinal MRI findings in Burkholderia pseudomallei infection. J Neuroimaging 26:75–82.
    497.
    Limmathurotsakul D, Kanoksil M, Wuthiekanun V, Kitphati R, deStavola B, Day NP, Peacock SJ. 2013. Activities of daily living associated with acquisition of melioidosis in northeast Thailand: a matched case-control study. PLoS Negl Trop Dis 7:e2072.
    498.
    Carey IM, Critchley JA, DeWilde S, Harris T, Hosking FJ, Cook DG. 2018. Risk of infection in type 1 and type 2 diabetes compared with the general population: a matched cohort study. Diabetes Care 41:513.
    499.
    Shah BR, Hux JE. 2003. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 26:510.
    500.
    Geerlings SE, Hoepelman AI. 1999. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol 26:259–6265.
    501.
    Graves DT, Kayal RA. 2008. Diabetic complications and dysregulated innate immunity. Front Biosci 13:1227–1239.
    502.
    Mayer-Scholl A, Averhoff P, Zychlinsky A. 2004. How do neutrophils and pathogens interact? Curr Opin Microbiol 7:62–66.
    503.
    Hodgson K, Morris J, Bridson T, Govan B, Rush C, Ketheesan N. 2015. Immunological mechanisms contributing to the double burden of diabetes and intracellular bacterial infections. Immunology 144:171–185.
    504.
    Hodgson KA, Govan BL, Walduck AK, Ketheesan N, Morris JL. 2013. Impaired early cytokine responses at the site of infection in a murine model of type 2 diabetes and melioidosis comorbidity. Infect Immun 81:470–477.
    505.
    Dunachie SJ, Jenjaroen K, Reynolds CJ, Quigley KJ, Sergeant R, Sumonwiriya M, Chaichana P, Chumseng S, Ariyaprasert P, Lassaux P, Gourlay L, Promwong C, Teparrukkul P, Limmathurotsakul D, Day NPJ, Altmann DM, Boyton RJ. 2017. Infection with Burkholderia pseudomallei—immune correlates of survival in acute melioidosis. Sci Rep 7:12143.
    506.
    Kulsantiwong P, Pudla M, Boondit J, Wikraiphat C, Dunachie SJ, Chantratita N, Utaisincharoen P. 2016. Burkholderia pseudomallei induces IL-23 production in primary human monocytes. Med Microbiol Immunol 205:255–260.
    507.
    Kewcharoenwong C, Rinchai D, Nithichanon A, Bancroft GJ, Ato M, Lertmemongkolchai G. 2016. Glibenclamide impairs responses of neutrophils against Burkholderia pseudomallei by reduction of intracellular glutathione. Sci Rep 6:34794.
    508.
    Kewcharoenwong C, Rinchai D, Utispan K, Suwannasaen D, Bancroft GJ, Ato M, Lertmemongkolchai G. 2013. Glibenclamide reduces pro-inflammatory cytokine production by neutrophils of diabetes patients in response to bacterial infection. Sci Rep 3:3363.
    509.
    Koh GCKW, Maude RR, Schreiber MF, Limmathurotsakul D, Wiersinga WJ, Wuthiekanun V, Lee SJ, Mahavanakul W, Chaowagul W, Chierakul W, White NJ, van der Poll T, Day NPJ, Dougan G, Peacock SJ. 2011. Glyburide is anti-inflammatory and associated with reduced mortality in melioidosis. Clin Infect Dis 52:717–725.
    510.
    Limmathurotsakul D, Chaowagul W, Chierakul W, Stepniewska K, Maharjan B, Wuthiekanun V, White NJ, Day NP, Peacock SJ. 2006. Risk factors for recurrent melioidosis in northeast Thailand. Clin Infect Dis 43:979–986.
    511.
    Chierakul W, Wuthiekanun V, Chaowagul W, Amornchai P, Cheng AC, White NJ, Day NP, Peacock SJ. 2005. Short report: disease severity and outcome of melioidosis in HIV coinfected individuals. Am J Trop Med Hyg 73:1165–1166.
    512.
    Fong SM, Wong KJ, Fukushima M, Yeo TW. 2015. Thalassemia major is a major risk factor for pediatric melioidosis in Kota Kinabalu, Sabah, Malaysia. Clin Infect Dis 60:1802–1807.
    513.
    Abraham C, Cho JH. 2006. Functional consequences of NOD2 (CARD15) mutations. Inflamm Bowel Dis 12:641–650.
    514.
    Pan H, Dai Y, Tang S, Wang J. 2012. Polymorphisms of NOD2 and the risk of tuberculosis: a validation study in the Chinese population. Int J Immunogenet 39:233–240.
    515.
    Myers ND, Chantratita N, Berrington WR, Chierakul W, Limmathurotsakul D, Wuthiekanun V, Robertson JD, Liggitt HD, Peacock SJ, Skerrett SJ, West TE. 2014. The role of NOD2 in murine and human melioidosis. J Immunol 192:300–307.
    516.
    West TE, Chierakul W, Chantratita N, Limmathurotsakul D, Wuthiekanun V, Emond MJ, Hawn TR, Peacock SJ, Skerrett SJ. 2012. Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis. Genes Immun 13:38–46.
    517.
    Limmathurotsakul D, Chaowagul W, Chantratita N, Wuthiekanun V, Biaklang M, Tumapa S, White NJ, Day NPJ, Peacock SJ. 2008. A simple scoring system to differentiate between relapse and re-infection in patients with recurrent melioidosis. PLoS Negl Trop Dis 2:e327.
    518.
    Chaowagul W, Suputtamongkol Y, Dance DA, Rajchanuvong A, Pattara J, White NJ. 1993. Relapse in melioidosis: incidence and risk factors. J Infect Dis 168:1181–1185.
    519.
    Sarovich DS, Ward L, Price EP, Mayo M, Pitman MC, Baird RW, Currie BJ. 2014. Recurrent melioidosis in the Darwin Prospective Melioidosis Study: improving therapies mean that relapse cases are now rare. J Clin Microbiol 52:650–653.
    520.
    Chetchotisakd P, Chierakul W, Chaowagul W, Anunnatsiri S, Phimda K, Mootsikapun P, Chaisuksant S, Pilaikul J, Thinkhamrop B, Phiphitaporn S, Susaengrat W, Toondee C, Wongrattanacheewin S, Wuthiekanun V, Chantratita N, Thaipadungpanit J, Day NP, Limmathurotsakul D, Peacock SJ. 2014. Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial. Lancet 383:807–814.
    521.
    Newland RC. 1969. Chronic melioidosis: a case in Sydney. Pathology 1:149–152.
    522.
    Gee JE, Gulvik CA, Elrod MG, Batra D, Rowe LA, Sheth M, Hoffmaster AR. 2017. Phylogeography of Burkholderia pseudomallei isolates, Western Hemisphere. Emerg Infect Dis 23:1133–1138.
    523.
    Johnson AB, Ali N. 1990. Reactivation of latent melioidosis. Postgrad Med J 66:732–733.
    524.
    Shaaban H, Hallit R, Slim J, Sree A, Sensakovic JW. 2014. Reactivation of latent melioidosis presenting with acute pyelonephritis and bacteremia. Avicenna J Med 4:20–21.
    525.
    Leelarasamee A, Bovornkitti S. 1989. Melioidosis: review and update. Rev Infect Dis 11:413–425.
    526.
    Dance D. 2014. Treatment and prophylaxis of melioidosis. Int J Antimicrob Agents 43:310–318.
    527.
    White NJ, Dance DA, Chaowagul W, Wattanagoon Y, Wuthiekanun V, Pitakwatchara N. 1989. Halving of mortality of severe melioidosis by ceftazidime. Lancet ii:697–701.
    528.
    Sookpranee M, Boonma P, Susaengrat W, Bhuripanyo K, Punyagupta S. 1992. Multicenter prospective randomized trial comparing ceftazidime plus co-trimoxazole with chloramphenicol plus doxycycline and co-trimoxazole for treatment of severe melioidosis. Antimicrob Agents Chemother 36:158–162.
    529.
    Chierakul W, Anunnatsiri S, Short JM, Maharjan B, Mootsikapun P, Simpson AJ, Limmathurotsakul D, Cheng AC, Stepniewska K, Newton PN, Chaowagul W, White NJ, Peacock SJ, Day NP, Chetchotisakd P. 2005. Two randomized controlled trials of ceftazidime alone versus ceftazidime in combination with trimethoprim-sulfamethoxazole for the treatment of severe melioidosis. Clin Infect Dis 41:1105–1113.
    530.
    Chierakul W, Anunnatsiri S, Chaowagul W, Peacock SJ, Chetchotisakd P, Day NP. 2007. Addition of trimethoprim-sulfamethoxazole to ceftazidime during parenteral treatment of melioidosis is not associated with a long-term outcome benefit. Clin Infect Dis 45:521–523.
    531.
    Suputtamongkol Y, Rajchanuwong A, Chaowagul W, Dance DA, Smith MD, Wuthiekanun V, Walsh AL, Pukrittayakamee S, White NJ. 1994. Ceftazidime vs. amoxicillin/clavulanate in the treatment of severe melioidosis. Clin Infect Dis 19:846–853.
    532.
    Cheng AC, Chierakul W, Chaowagul W, Chetchotisakd P, Limmathurotsakul D, Dance DA, Peacock SJ, Currie BJ. 2008. Consensus guidelines for dosing of amoxicillin-clavulanate in melioidosis. Am J Trop Med Hyg 78:208–209.
    533.
    Chierakul W, Wangboonskul J, Singtoroj T, Pongtavornpinyo W, Short JM, Maharjan B, Wuthiekanun V, Dance DAB, Teparrukkul P, Lindegardh N, Peacock SJ, Day NP, Chaowagul W, White NJ. 2006. Pharmacokinetic and pharmacodynamic assessment of co-amoxiclav in the treatment of melioidosis. J Antimicrob Chemother 58:1215–1220.
    534.
    Rajchanuvong A, Chaowagul W, Suputtamongkol Y, Smith MD, Dance DA, White NJ. 1995. A prospective comparison of co-amoxiclav and the combination of chloramphenicol, doxycycline, and co-trimoxazole for the oral maintenance treatment of melioidosis. Trans R Soc Trop Med Hyg 89:546–549.
    535.
    Chaowagul W, Simpson AJ, Suputtamongkol Y, White NJ. 1999. Empirical cephalosporin treatment of melioidosis. Clin Infect Dis 28:1328.
    536.
    Ashdown LR. 1988. In vitro activities of the newer beta-lactam and quinolone antimicrobial agents against Pseudomonas pseudomallei. Antimicrob Agents Chemother 32:1435–1436.
    537.
    Smith MD, Wuthiekanun V, Walsh AL, White NJ. 1996. In-vitro activity of carbapenem antibiotics against beta-lactam susceptible and resistant strains of Burkholderia pseudomallei. J Antimicrob Chemother 37:611–615.
    538.
    Walsh AL, Smith MD, Wuthiekanun V, White NJ. 1995. Postantibiotic effects and Burkholderia (Pseudomonas) pseudomallei: evaluation of current treatment. Antimicrob Agents Chemother 39:2356–2358.
    539.
    Lipsitz R, Garges S, Aurigemma R, Baccam P, Blaney DD, Cheng AC, Currie BJ, Dance D, Gee JE, Larsen J, Limmathurotsakul D, Morrow MG, Norton R, O’Mara E, Peacock SJ, Pesik N, Rogers LP, Schweizer HP, Steinmetz I, Tan G, Tan P, Wiersinga WJ, Wuthiekanun V, Smith TL. 2012. Workshop on treatment of and postexposure prophylaxis for Burkholderia pseudomallei and B. mallei infection, 2010. Emerg Infect Dis 18:e2.
    540.
    Currie BJ. 2014. Melioidosis: the 2014 revised RDH guideline. Northern Territ Dis Control Bull 21:4–8.
    541.
    Cheng AC, McBryde ES, Wuthiekanun V, Chierakul W, Amornchai P, Day NP, White NJ, Peacock SJ. 2009. Dosing regimens of cotrimoxazole (trimethoprim-sulfamethoxazole) for melioidosis. Antimicrob Agents Chemother 53:4193–4199.
    542.
    Chaowagul W, Simpson AJ, Suputtamongkol Y, Smith MD, Angus BJ, White NJ. 1999. A comparison of chloramphenicol, trimethoprim-sulfamethoxazole, and doxycycline with doxycycline alone as maintenance therapy for melioidosis. Clin Infect Dis 29:375–380.
    543.
    Chaowagul W, Chierakul W, Simpson AJ, Short JM, Stepniewska K, Maharjan B, Rajchanuvong A, Busarawong D, Limmathurotsakul D, Cheng AC, Wuthiekanun V, Newton PN, White NJ, Day NP, Peacock SJ. 2005. Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis. Antimicrob Agents Chemother 49:4020–4025.
    544.
    Pitman MC, Luck T, Marshall CS, Anstey NM, Ward L, Currie BJ. 2015. Intravenous therapy duration and outcomes in melioidosis: a new treatment paradigm. PLoS Negl Trop Dis 9:e0003586.
    545.
    Gibney KB, Cheng AC, Currie BJ. 2008. Cutaneous melioidosis in the tropical top end of Australia: a prospective study and review of the literature. Clin Infect Dis 47:603–609.
    546.
    Cheng AC, Dasari P, Currie BJ. 2004. Granulocyte colony-stimulating factor and an in vitro whole blood model of melioidosis. Eur J Clin Microbiol Infect Dis 23:205–207.
    547.
    Cheng AC, Limmathurotsakul D, Chierakul W, Getchalarat N, Wuthiekanun V, Stephens DP, Day NP, White NJ, Chaowagul W, Currie BJ, Peacock SJ. 2007. A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand. Clin Infect Dis 45:308–314.
    548.
    Cheng AC, Stephens DP, Anstey NM, Currie BJ. 2004. Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis. Clin Infect Dis 38:32–37.
    549.
    Currie BJ, Fisher DA, Howard DM, Burrow JN, Lo D, Selva-Nayagam S, Anstey NM, Huffam SE, Snelling PL, Marks PJ, Stephens DP, Lum GD, Jacups SP, Krause VL. 2000. Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature. Clin Infect Dis 31:981–986.
    550.
    Simpson AJ, Suputtamongkol Y, Smith MD, Angus BJ, Rajanuwong A, Wuthiekanun V, Howe PA, Walsh AL, Chaowagul W, White NJ. 1999. Comparison of imipenem and ceftazidime as therapy for severe melioidosis. Clin Infect Dis 29:381–387.
    551.
    Toda A, Ohki H, Yamanaka T, Murano K, Okuda S, Kawabata K, Hatano K, Matsuda K, Misumi K, Itoh K, Satoh K, Inoue S. 2008. Synthesis and SAR of novel parenteral anti-pseudomonal cephalosporins: discovery of FR264205. Bioorg Med Chem Lett 18:4849–4852.
    552.
    Hong MC, Hsu DI, Bounthavong M. 2013. Ceftolozane/tazobactam: a novel antipseudomonal cephalosporin and beta-lactamase-inhibitor combination. Infect Drug Resist 6:215–223.
    553.
    Slack A, Parsonson F, Cronin K, Engler C, Norton R. 2018. Activity of ceftolozane-tazobactam against Burkholderia pseudomallei. Am J Trop Med Hyg 99:281–282.
    554.
    Chaowagul W, Suputtamongkul Y, Smith MD, White NJ. 1997. Oral fluoroquinolones for maintenance treatment of melioidosis. Trans R Soc Trop Med Hyg 91:599–601.
    555.
    Barnes KB, Hamblin KA, Richards MI, Laws TR, Vente A, Atkins HS, Harding SV. 2017. Demonstrating the protective efficacy of the novel fluoroquinolone finafloxacin against an inhalational exposure to Burkholderia pseudomallei. Antimicrob Agents Chemother 61:e00082-17.
    556.
    Tomaras AP, McPherson CJ, Kuhn M, Carifa A, Mullins L, George D, Desbonnet C, Eidem TM, Montgomery JI, Brown MF, Reilly U, Miller AA, O’Donnell JP. 2014. LpxC inhibitors as new antibacterial agents and tools for studying regulation of lipid A biosynthesis in Gram-negative pathogens. mBio 5:e01551-14.
    557.
    Sengyee S, Saiprom N, Paksanont S, Limmathurotsakul D, Wuthiekanun V, Chantratita N. 2017. Susceptibility of clinical isolates of Burkholderia pseudomallei to a lipid A biosynthesis inhibitor. Am J Trop Med Hyg 97:62–67.
    558.
    Sivalingam SP, Sim SH, Jasper LCW, Wang D, Liu Y, Ooi EE. 2008. Pre- and post-exposure prophylaxis of experimental Burkholderia pseudomallei infection with doxycycline, amoxicillin/clavulanic acid and co-trimoxazole. J Antimicrob Chemother 61:674–678.
    559.
    Barnes KB, Steward J, Thwaite JE, Lever MS, Davies CH, Armstrong SJ, Laws TR, Roughley N, Harding SV, Atkins TP, Simpson AJH, Atkins HS. 2013. Trimethoprim/sulfamethoxazole (co-trimoxazole) prophylaxis is effective against acute murine inhalational melioidosis and glanders. Int J Antimicrob Agents 41:552–557.
    560.
    Majoni SW, Hughes JT, Heron B, Currie BJ. 2018. Trimethoprim+sulfamethoxazole reduces rates of melioidosis in high-risk hemodialysis patients. Kidney Int Rep 3:160–167.
    561.
    Chau KWT, Smith S, Kang K, Dheda S, Hanson J. 2018. Antibiotic prophylaxis for melioidosis in patients receiving hemodialysis in the tropics? One size does not fit all. Am J Trop Med Hyg 99:597–600.
    562.
    Inglis TJ, Sousa AQ. 2009. The public health implications of melioidosis. Braz J Infect Dis 13:59–66.
    563.
    Boyd R, McGuinness S, Draper A, Neilson M, Krause V. 2016. melioidosis awareness campaign …….don’t get melioidosis…. Northern Territ Dis Control Bull 23:1–4.
    564.
    McRobb E, Kaestli M, Mayo M, Price EP, Sarovich DS, Godoy D, Spratt BG, Currie BJ. 2013. Melioidosis from contaminated bore water and successful UV sterilization. Am J Trop Med Hyg 89:367–368.
    565.
    Rose LJ, Rice EW, Jensen B, Murga R, Peterson A, Donlan RM, Arduino MJ. 2005. Chlorine inactivation of bacterial bioterrorism agents. Appl Environ Microbiol 71:566–568.
    566.
    Cheung RCF, Ng TB, Wong JH, Chan WY. 2015. Chitosan: an update on potential biomedical and pharmaceutical applications. Mar Drugs 13:5156–5186.
    567.
    Kamjumphol W, Chareonsudjai P, Chareonsudjai S. 2018. Antibacterial activity of chitosan against Burkholderia pseudomallei. Microbiologyopen 7:e00534.
    568.
    Na-ngam N, Angkititakul S, Noimay P, Thamlikitkul V. 2004. The effect of quicklime (calcium oxide) as an inhibitor of Burkholderia pseudomallei. Trans R Soc Trop Med Hyg 98:337–341.
    569.
    Sommanustweechai A, Kasantikul T, Somsa W, Wongratanacheewin S, Sermswan RW, Kongmakee P, Thomas W, Kamolnorranath S, Siriaroonrat B, Bush M, Banlunara W. 2013. Environmental management procedures following fatal melioidosis in a captive chimpanzee (Pan troglodytes). J Zoo Wildl Med 44:475–479.
    570.
    Chansrichavala P, Wongsuwan N, Suddee S, Malasit M, Hongsuwan M, Wannapinij P, Kitphati R, Day NPJ, Michie S, Peacock SJ, Limmathurotsakul D. 2015. Public awareness of melioidosis in Thailand and potential use of video clips as educational tools. PLoS One 10:e0121311.
    571.
    Suntornsut P, Wongsuwan N, Malasit M, Kitphati R, Michie S, Peacock SJ, Limmathurotsakul D. 2016. Barriers and recommended interventions to prevent melioidosis in northeast Thailand: a focus group study using the behaviour change wheel. PLoS Negl Trop Dis 10:e0004823.
    572.
    Green RN, Tuffnell PG. 1968. Laboratory acquired melioidosis. Am J Med 44:599–605.
    573.
    Schlech WF, Turchik JB, Westlake RE, Klein GC, Band JD, Weaver RE. 1981. Laboratory-acquired infection with Pseudomonas pseudomallei (melioidosis). N Engl J Med 305:1133–1135.
    574.
    Vlieghe E, Kruy L, Smet B, Kham C, Veng CH, Phe T, Koole O, Thai S, Lynen L, Jacobs J. 2011. Melioidosis, Phnom Penh, Cambodia. Emerg Infect Dis 17:1289–1292.
    575.
    Limmathurotsakul D, Wuthiekanun V, Wongsuvan G, Pangmee S, Amornchai P, Teparrakkul P, Teerawattanasook N, Day NPJ, Peacock SJ. 2011. Repeat blood culture positive for B. pseudomallei indicates an increased risk of death from melioidosis. Am J Trop Med Hyg 84:858–861.
    576.
    Thatrimontrichai A, Maneenil G. 2012. Neonatal melioidosis: systematic review of the literature. Pediatr Infect Dis J 31:1195–1197.
    577.
    Rammaert B, Beaute J, Borand L, Hem S, Buchy P, Goyet S, Overtoom R, Angebault C, Te V, Try PL, Mayaud C, Vong S, Guillard B. 2011. Pulmonary melioidosis in Cambodia: a prospective study. BMC Infect Dis 11:126.
    578.
    Om C, Daily F, Vlieghe E, McLaughlin JC, McLaws M-L. 2016. “If it’s a broad spectrum, it can shoot better”: inappropriate antibiotic prescribing in Cambodia. Antimicrob Resist Infect Control 5:58.
    579.
    Puthucheary SD, Parasakthi N, Lee MK. 1992. Septicaemic melioidosis: a review of 50 cases from Malaysia. Trans R Soc Trop Med Hyg 86:683–685.
    580.
    Wright SW, Emond MJ, Lovelace-Macon L, Ducken D, Kashima J, Hantrakun V, Chierakul W, Teparrukkul P, Chantratita N, Limmathurotsakul D, West TE. 2019. Exonic sequencing identifies TLR1 genetic variation associated with mortality in Thais with melioidosis. Emerg Microbes Infect 8:282–290.
    581.
    West TE, Chantratita N, Chierakul W, Limmathurotsakul D, Wuthiekanun V, Myers ND, Emond MJ, Wurfel MM, Hawn TR, Peacock SJ, Skerrett SJ. 2013. Impaired TLR5 functionality is associated with survival in melioidosis. J Immunol 190:3373–3379.
    582.
    Chaichana P, Chantratita N, Brod F, Koosakulnirand S, Jenjaroen K, Chumseng S, Sumonwiriya M, Burtnick MN, Brett PJ, Teparrukkul P, Limmathurotsakul D, Day NPJ, Dunachie SJ, West TE. 2017. A nonsense mutation in TLR5 is associated with survival and reduced IL-10 and TNF-α levels in human melioidosis. PLoS Negl Trop Dis 11:e0005587.
    583.
    West TE, Myers ND, Chantratita N, Chierakul W, Limmathurotsakul D, Wuthiekanun V, Miao EA, Hajjar AM, Peacock SJ, Liggitt HD, Skerrett SJ. 2014. NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis. PLoS Negl Trop Dis 8:e3178.
    584.
    Chantratita N, Tandhavanant S, Myers ND, Chierakul W, Robertson JD, Mahavanakul W, Singhasivanon P, Emond MJ, Peacock SJ, West TE. 2014. Screen of whole blood responses to flagellin identifies TLR5 variation associated with outcome in melioidosis. Genes Immun 15:63–71.
    585.
    Limmathurotsakul D, Funnell SG, Torres AG, Morici LA, Brett PJ, Dunachie S, Atkins T, Altmann DM, Bancroft G, Peacock SJ, Steering Group on Melioidosis Vaccine Development. 2015. Consensus on the development of vaccines against naturally acquired melioidosis. Emerg Infect Dis doi:
    586.
    Hatcher CL, Muruato LA, Torres AG. 2015. Recent advances in Burkholderia mallei and B. pseudomallei research. Curr Trop Med Rep 2:62–69.
    587.
    Hogan RJ, Lafontaine ER. 2019. Antibodies are major drivers of protection against lethal aerosol infection with highly pathogenic Burkholderia spp. mSphere 4:e00674-18.
    588.
    Peacock SJ, Limmathurotsakul D, Lubell Y, Koh GC, White LJ, Day NP, Titball RW. 2012. Melioidosis vaccines: a systematic review and appraisal of the potential to exploit biodefense vaccines for public health purposes. PLoS Negl Trop Dis 6:e1488.
    589.
    Titball RW, Burtnick MN, Bancroft GJ, Brett P. 2017. Burkholderia pseudomallei and Burkholderia mallei vaccines: are we close to clinical trials? Vaccine 35:5981–5989.
    590.
    Cuccui J, Easton A, Chu KK, Bancroft GJ, Oyston PCF, Titball RW, Wren BW. 2007. Development of signature-tagged mutagenesis in Burkholderia pseudomallei to identify genes important in survival and pathogenesis. Infect Immun 75:1186–1195.
    591.
    Breitbach K, Kohler J, Steinmetz I. 2008. Induction of protective immunity against Burkholderia pseudomallei using attenuated mutants with defects in the intracellular life cycle. Trans R Soc Trop Med Hyg 102(Suppl 1):S89–S94.
    592.
    Silva EB, Goodyear A, Sutherland MD, Podnecky NL, Gonzalez-Juarrero M, Schweizer HP, Dow SW. 2013. Correlates of immune protection following cutaneous immunization with an attenuated Burkholderia pseudomallei vaccine. Infect Immun 81:4626–4634.
    593.
    Khakhum N, Bharaj P, Myers JN, Tapia D, Kilgore PB, Ross BN, Walker DH, Endsley JJ, Torres AG. 2019. Burkholderia pseudomallei ΔtonB Δhcp1 live attenuated vaccine strain elicits full protective immunity against aerosolized melioidosis infection. mSphere 4:e00570-18.
    594.
    Scott AE, Laws TR, D’Elia RV, Margaret GMS, Nandi T, Williamson ED, Tan P, Prior JL, Atkins TP. 2013. Protection against experimental melioidosis following immunization with live Burkholderia thailandensis expressing a manno-heptose capsule. Clin Vaccine Immunol 20:1041–1047.
    595.
    Patel N, Conejero L, De Reynal M, Easton A, Bancroft GJ, Titball RW. 2011. Development of vaccines against burkholderia pseudomallei. Front Microbiol 2:198.
    596.
    Barnes JL, Ketheesan N. 2007. Development of protective immunity in a murine model of melioidosis is influenced by the source of Burkholderia pseudomallei antigens. Immunol Cell Biol 85:551–557.
    597.
    Puangpetch A, Anderson R, Huang YY, Saengsot R, Sermswan RW, Wongratanacheewin S. 2014. Comparison of the protective effects of killed Burkholderia pseudomallei and CpG oligodeoxynucleotide against live challenge. Vaccine 32:5983–5988.
    598.
    Sarkar-Tyson M, Smither SJ, Harding SV, Atkins TP, Titball RW. 2009. Protective efficacy of heat-inactivated B. thailandensis, B. mallei or B. pseudomallei against experimental melioidosis and glanders. Vaccine 27:4447–4451.
    599.
    Burtnick MN, Shaffer TL, Ross BN, Muruato LA, Sbrana E, DeShazer D, Torres AG, Brett PJ. 2018. Development of subunit vaccines that provide high-level protection and sterilizing immunity against acute inhalational melioidosis. Infect Immun 86:e00724-17.
    600.
    Nelson M, Prior JL, Lever MS, Jones HE, Atkins TP, Titball RW. 2004. Evaluation of lipopolysaccharide and capsular polysaccharide as subunit vaccines against experimental melioidosis. J Med Microbiol 53:1177–1182.
    601.
    Whitlock GC, Deeraksa A, Qazi O, Judy BM, Taylor K, Propst KL, Duffy AJ, Johnson K, Kitto GB, Brown KA, Dow SW, Torres AG, Estes DM. 2010. Protective response to subunit vaccination against intranasal Burkholderia mallei and B. pseudomallei challenge. Procedia Vaccinol 2:73–77.
    602.
    Nieves W, Asakrah S, Qazi O, Brown KA, Kurtz J, AuCoin DP, McLachlan JB, Roy CJ, Morici LA. 2011. A naturally derived outer-membrane vesicle vaccine protects against lethal pulmonary Burkholderia pseudomallei infection. Vaccine 29:8381–8389.
    603.
    Nieves W, Petersen H, Judy BM, Blumentritt CA, Russell-Lodrigue K, Roy CJ, Torres AG, Morici LA. 2014. A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis. Clin Vaccine Immunol 21:747–754.
    604.
    Petersen H, Nieves W, Russell-Lodrigue K, Roy CJ, Morici LA. 2014. Evaluation of a Burkholderia pseudomallei outer membrane vesicle vaccine in nonhuman primates. Procedia Vaccinol 8:38–42.
    605.
    Scott AE, Ngugi SA, Laws TR, Corser D, Lonsdale CL, D’Elia RV, Titball RW, Williamson ED, Atkins TP, Prior JL. 2014. Protection against experimental melioidosis following immunisation with a lipopolysaccharide-protein conjugate. J Immunol Res 2014:392170.
    606.
    Scott AE, Burtnick MN, Stokes MGM, Whelan AO, Williamson ED, Atkins TP, Prior JL, Brett PJ. 2014. Burkholderia pseudomallei capsular polysaccharide conjugates provide protection against acute melioidosis. Infect Immun 82:3206–3213.
    607.
    Muruato LA, Tapia D, Hatcher CL, Kalita M, Brett PJ, Gregory AE, Samuel JE, Titball RW, Torres AG. 2017. Use of reverse vaccinology in the design and construction of nanoglycoconjugate vaccines against Burkholderia pseudomallei. Clin Vaccine Immunol 24:e00206-17.
    608.
    Gregory AE, Judy BM, Qazi O, Blumentritt CA, Brown KA, Shaw AM, Torres AG, Titball RW. 2015. A gold nanoparticle-linked glycoconjugate vaccine against Burkholderia mallei. Nanomedicine 11:447–456.
    609.
    Dance DAB. 2005. Melioidosis and glanders as possible biological weapons, p 99–145. In Fong IW, Alibek K (ed), Bioterrorism and infectious agents: a new dilemma for the 21st century. Springer US, Boston, MA.
    610.
    Dvorak GD, Spickler AR. 2008. Glanders. J Am Vet Med Assoc 233:570–577.
    611.
    Rotz LD, Khan AS, Lillibridge SR, Ostroff SM, Hughes JM. 2002. Public health assessment of potential biological terrorism agents. Emerg Infect Dis 8:225–230.
    612.
    Wiersinga WJ, van der Poll T, White NJ, Day NP, Peacock SJ. 2006. Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei. Nat Rev Microbiol 4:272.
    613.
    Shams AM, Rose LJ, Hodges L, Arduino MJ. 2007. Survival of Burkholderia pseudomallei on environmental surfaces. Appl Environ Microbiol 73:8001–8004.
    614.
    Wuthiekanun V, Smith MD, White NJ. 1995. Survival of Burkholderia pseudomallei in the absence of nutrients. Trans R Soc Trop Med Hyg 89:491.
    615.
    Estes DM, Dow SW, Schweizer HP, Torres AG. 2010. Present and future therapeutic strategies for melioidosis and glanders. Expert Rev Anti-infect Ther 8:325–338.
    616.
    Bhengsri S, Lertiendumrong J, Baggett HC, Thamthitiwat S, Chierakul W, Tisayaticom K, Tanwisaid K, Chantra S, Kaewkungwal J. 2013. Economic burden of bacteremic melioidosis in eastern and northeastern, [sic] Thailand. Am J Trop Med Hyg 89:369–373.
    617.
    Chatterjee S, Riewpaiboon A, Piyauthakit P, Riewpaiboon W, Boupaijit K, Panpuwong N, Archavanuntagul V. 2011. Cost of diabetes and its complications in Thailand: a complete picture of economic burden. Health Soc Care Community 19:289–298.
    618.
    Liljas B. 1998. How to calculate indirect costs in economic evaluations. Pharmacoeconomics 13:1–7.
    619.
    Huy R, Wichmann O, Beatty M, Ngan C, Duong S, Margolis HS, Vong S. 2009. Cost of dengue and other febrile illnesses to households in rural Cambodia: a prospective community-based case-control study. BMC Public Health 9:155.
    620.
    Hantrakun V, Chierakul W, Chetchotisakd P, Anunnatsiri S, Currie BJ, Peacock SJ, Day NP, Cheah PY, Limmathurotsakul D, Lubell Y. 2015. Cost-effectiveness analysis of parenteral antimicrobials for acute melioidosis in Thailand. Trans R Soc Trop Med Hyg 109:803.
    621.
    Cheng AC, Fisher DA, Anstey NM, Stephens DP, Jacups SP, Currie BJ. 2004. Outcomes of patients with melioidosis treated with meropenem. Antimicrob Agents Chemother 48:1763–1765.
    622.
    Malczewski AB, Oman KM, Norton RE, Ketheesan N. 2005. Clinical presentation of melioidosis in Queensland, Australia. Trans R Soc Trop Med Hyg 99:856–860.
    623.
    Chaiwarith R, Patiwetwitoon P, Supparatpinyo K, Sirisanthana T. 2005. Melioidosis at Maharaj Nakorn Chiang Mai Hospital, Thailand. J Infect Dis Antimicrob Agents 22:45–51.
    624.
    Jabbar Z, Currie BJ. 2013. Melioidosis and the kidney. Nephrology (Carlton) 18:169–175.
    625.
    Inglis TJ. 2010. The treatment of melioidosis. Pharmaceuticals (Basel) 3:1296–1303.

    Author Bios

    I. Gassiep
    Pathology Queensland, Townsville Hospital, Townsville, Queensland, Australia
    Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
    I. Gassiep completed medical school through Monash University Australia & Malaysia. His early career aspirations in infectious diseases were shaped by his upbringing in South Africa, and his interest in tropical infectious diseases was sparked by the time he spent in the Malaysian health care system. He is currently an Infectious Diseases Physician and Clinical Microbiologist working in The Mater Hospital, Brisbane, Queensland, Australia.
    M. Armstrong
    Pathology Queensland, Townsville Hospital, Townsville, Queensland, Australia
    M. Armstrong received his medical degree from the University of Otago, New Zealand, and is a registrar training in Infectious Diseases and Clinical Microbiology. Currently he is based in Townsville, Australia, to complete training in Clinical Microbiology. Before Townsville he worked in diverse settings, including Timor-Leste. He has an interest in tropical medicine, having just completed his master of public health and tropical medicine through James Cook University.
    Pathology Queensland, Townsville Hospital, Townsville, Queensland, Australia
    Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
    R. Norton trained as a clinical microbiologist at The Institute of Medical and Veterinary Science, Adelaide, Australia. He has worked in a variety of clinical positions, including 5 years in Australian indigenous communities. He is currently Director of Pathology and Microbiology at Townsville Hospital, Queensland, Australia. In his current capacity he has collaborated with researchers locally and internationally on projects relating to melioidosis. This is a disease which is endemic in this region, and he has had an interest in this condition for the last 20 years. He was a coauthor in the CDC-sponsored guideline (2010) on Diagnostics for Melioidosis.

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    Clinical Microbiology Reviews
    Volume 33Number 218 March 2020
    eLocator: e00006-19

    History

    Published online: 11 March 2020

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    KEYWORDS

    1. Burkholderia pseudomallei
    2. melioidosis

    Contributors

    Authors

    I. Gassiep
    Pathology Queensland, Townsville Hospital, Townsville, Queensland, Australia
    Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
    M. Armstrong
    Pathology Queensland, Townsville Hospital, Townsville, Queensland, Australia
    Pathology Queensland, Townsville Hospital, Townsville, Queensland, Australia
    Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia

    Notes

    Address correspondence to R. Norton, [email protected].

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  • Clinical Microbiology ReviewsArticle
    Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

    Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

    SUMMARY

    Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed.

    REFERENCES

    1.
    Abdel-Wahab A. et al.2002. Dynamics of gametocytes among Plasmodium falciparum clones in natural infections in an area of highly seasonal transmission. J. Infect. Dis. 185:1838–1842.
    2.
    Abu-Raddad L. J., Patnaik P., and Kublin J. G..2006. Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa. Science 314:1603–1606.
    3.
    Adjuik M. et al.2004. Artesunate combinations for treatment of malaria: meta-analysis. Lancet 363:9–17.
    4.
    Akim N. I. et al.2000. Dynamics of P. falciparum gametocytemia in symptomatic patients in an area of intense perennial transmission in Tanzania. Am. J. Trop. Med. Hyg. 63:199–203.
    5.
    Alano P.2007. Plasmodium falciparum gametocytes: still many secrets of a hidden life. Mol. Microbiol. 66:291–302.
    6.
    Alano P. et al.1995. COS cell expression cloning of Pfg377, a Plasmodium falciparum gametocyte antigen associated with osmiophilic bodies. Mol. Biochem. Parasitol. 74:143–156.
    7.
    Ali E. et al.2006. Increased density but not prevalence of gametocytes following drug treatment of Plasmodium falciparum. Trans. R. Soc. Trop. Med. Hyg. 100:176–183.
    8.
    Alves F. P. et al.2005. Asymptomatic carriers of Plasmodium spp. as infection source for malaria vector mosquitoes in the Brazilian Amazon. J. Med. Entomol. 42:777–779.
    8a.
    .1887. Haematozoa of malaria. Br. Med. J. 1887:960–961.
    8b.
    .2007. Is malaria eradication possible? Lancet 370:1459.
    9.
    Aponte J. J. et al.2009. Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials. Lancet 374:1533–1542.
    10.
    Arakawa T. et al.2005. Nasal immunization with a malaria transmission-blocking vaccine candidate, Pfs25, induces complete protective immunity in mice against field isolates of Plasmodium falciparum. Infect. Immun. 73:7375–7380.
    11.
    Ashley E. A. et al.2004. Randomized, controlled dose-optimization studies of dihydroartemisinin-piperaquine for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand. J. Infect. Dis. 190:1773–1782.
    12.
    Ashley E. A. et al.2005. A randomized, controlled study of a simple, once-daily regimen of dihydroartemisinin-piperaquine for the treatment of uncomplicated, multidrug-resistant falciparum malaria. Clin. Infect. Dis. 41:425–432.
    13.
    Babiker A., Abdel-Muhsin A. A., Ranford-Cartwright L. C., Satti G., and Walliker D..1998. Characteristics of Plasmodium falciparum parasites that survive the lengthy dry season in eastern Sudan where malaria transmission is markedly seasonal. Am. J. Trop. Med. Hyg. 59:582–590.
    14.
    Babiker A. et al.1999. Detection of low level Plasmodium falciparum gametocytes using reverse transcriptase polymerase chain reaction. Mol. Biochem. Parasitol. 99:143–148.
    15.
    Babiker H. A. and Schneider P..2008. Application of molecular methods for monitoring transmission stages of malaria parasites. Biomed. Mater. 3:034007.
    16.
    Babiker H. A., Schneider P., and Reece S. E..2008. Gametocytes: insights gained during a decade of molecular monitoring. Trends Parasitol. 24:525–530.
    17.
    Bachmann A. et al.2009. Absence of erythrocyte sequestration and lack of multicopy gene family expression in Plasmodium falciparum from a splenectomized malaria patient. PLoS One 4:e7459.
    18.
    Baird J. K.2009. Resistance to therapies for infection by Plasmodium vivax. Clin. Microbiol. Rev. 22:508–534.
    19.
    Baird J. K. et al.1991. Evidence for specific suppression of gametocytemia by Plasmodium falciparum in residents of hyperendemic Irian Jaya. Am. J. Trop. Med. Hyg. 44:183–190.
    20.
    Baird J. K. and Surjadjaja C..2010. Consideration of ethics in primaquine therapy against malaria transmission. Trends Parasitol. 27:11–16.
    21.
    Baker D. A.2010. Malaria gametocytogenesis. Mol. Biochem. Parasitol. 172:57–65.
    22.
    Baker D. A., Daramola O., McCrossan M. V., Harmer J., and Targett G. A..1994. Subcellular localization of Pfs16, a Plasmodium falciparum gametocyte antigen. Parasitology 108:129–137.
    23.
    Barnes K. I., Chanda P., and Ab Barnabas G..2009. Impact of the large-scale deployment of artemether/lumefantrine on the malaria disease burden in Africa: case studies of South Africa, Zambia and Ethiopia. Malar. J. 8(Suppl. 1):S8.
    24.
    Barnes K. I. et al.2005. Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal, South Africa. PLoS Med. 2:e330.
    25.
    Barnes K. I. et al.2008. Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria. J. Infect. Dis. 197:1605–1613.
    26.
    Barnes K. I. and White N. J..2005. Population biology and antimalarial resistance: the transmission of antimalarial drug resistance in Plasmodium falciparum. Acta Trop. 94:230–240.
    27.
    Barr P. J. et al.1991. Recombinant Pfs25 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in experimental animals. J. Exp. Med. 174:1203–1208.
    28.
    Baton L. A. and Ranford-Cartwright L. C..2005. Do malaria ookinete surface proteins P25 and P28 mediate parasite entry into mosquito midgut epithelial cells? Malar. J. 4:15.
    29.
    Batty K. T. et al.1998. A pharmacokinetic and pharmacodynamic study of artesunate for vivax malaria. Am. J. Trop. Med. Hyg. 59:823–827.
    30.
    Beavogui A. H. et al.2010. Low infectivity of Plasmodium falciparum gametocytes to Anopheles gambiae following treatment with sulfadoxine-pyrimethamine in Mali. Int. J. Parasitol. 40:1213–1220.
    31.
    Bejon P. et al.2006. Thick blood film examination for Plasmodium falciparum malaria has reduced sensitivity and underestimates parasite density. Malar. J. 5:104.
    32.
    Bejon P. et al.2010. Stable and unstable malaria hotspots in longitudinal cohort studies in Kenya. PLoS Med. 7:e1000304.
    33.
    Beurskens M. et al.2009. Quantitative determination of Plasmodium vivax gametocytes by real-time quantitative nucleic acid sequence-based amplification in clinical samples. Am. J. Trop. Med. Hyg. 81:366–369.
    34.
    Bharti A. R. et al.2006. Experimental infection of the neotropical malaria vector Anopheles darlingi by human patient-derived Plasmodium vivax in the Peruvian Amazon. Am. J. Trop. Med. Hyg. 75:610–616.
    35.
    Bhattarai A. et al.2007. Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar. PLoS Med. 4:e309.
    36.
    Billker O. et al.1998. Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito. Nature 392:289–292.
    37.
    Billker O., Shaw M. K., Margos G., and Sinden R. E..1997. The roles of temperature, pH and mosquito factors as triggers of male and female gametogenesis of Plasmodium berghei in vitro. Parasitology 115:1–7.
    38.
    Birku Y., Mekonnen E., Bjorkman A., and Wolday D..2002. Delayed clearance of Plasmodium falciparum in patients with human immunodeficiency virus co-infection treated with artemisinin. Ethiop. Med. J. 40(Suppl. 1):17–26.
    39.
    Biswas S.2000. Formation of Plasmodium falciparum gametocytes in vivo and in vitro relates to transmission intensity. Ann. Trop. Med. Parasitol. 94:437–446.
    40.
    Blagborough A. M. and Sinden R. E..2009. Plasmodium berghei HAP2 induces strong malaria transmission-blocking immunity in vivo and in vitro. Vaccine 27:5187–5194.
    41.
    Blagborough A. M., Yoshida S., Sattabongkot J., Tsuboi T., and Sinden R. E..2010. Intranasal and intramuscular immunization with baculovirus dual expression system-based Pvs25 vaccine substantially blocks Plasmodium vivax transmission. Vaccine 28:6014–6020.
    42.
    Bockarie M. J. and Dagoro H..2006. Are insecticide-treated bednets more protective against Plasmodium falciparum than Plasmodium vivax-infected mosquitoes? Malar. J. 5:15.
    43.
    Boete C.2005. Malaria parasites in mosquitoes: laboratory models, evolutionary temptation and the real world. Trends Parasitol. 21:445–447.
    44.
    Boudin C., Lyannaz J., Bosseno M. F., Carnevale P., and Ambroise-Thomas P..1991. Epidemiology of Plasmodium falciparum in a rice field and a savanna area in Burkina Faso: seasonal fluctuations of gametocytaemia and malarial infectivity. Ann. Trop. Med. Parasitol. 85:377–385.
    45.
    Boudin C., Olivier M., Molez J. F., Chiron J. P., and Ambroise-Thomas P..1993. High human malarial infectivity to laboratory-bred Anopheles gambiae in a village in Burkina Faso. Am. J. Trop. Med. Hyg. 48:700–706.
    46.
    Boudin C., Robert V., Verhave J. P., Carnevale P., and Ambroise-Thomas P..1991. Plasmodium falciparum and P. malariae epidemiology in a West African village. Bull. World Health Organ. 69:199–205.
    47.
    Boudin C. et al.2004. Plasmodium falciparum transmission blocking immunity under conditions of low and high endemicity in Cameroon. Parasite Immunol. 26:105–110.
    48.
    Bouharoun-Tayoun H., Oeuvray C., Lunel F., and Druilhe P..1995. Mechanisms underlying the monocyte-mediated antibody-dependent killing of Plasmodium falciparum asexual blood stages. J. Exp. Med. 182:409–418.
    49.
    Bousema J. T. et al.2007. A longitudinal study of immune responses to Plasmodium falciparum sexual stage antigens in Tanzanian adults. Parasite Immunol. 29:309–317.
    50.
    Bousema J. T. et al.2008. Increased Plasmodium falciparum gametocyte production in mixed infections with P. malariae. Am. J. Trop. Med. Hyg. 78:442–448.
    51.
    Bousema J. T., Drakeley C. J., and Sauerwein R. W..2006. Sexual-stage antibody responses to P. falciparum in endemic populations. Curr. Mol. Med. 6:223–229.
    52.
    Bousema J. T. et al.2004. Plasmodium falciparum gametocyte carriage in asymptomatic children in western Kenya. Malar. J. 3:18.
    53.
    Bousema J. T. et al.2003. Treatment failure of pyrimethamine-sulphadoxine and induction of P. falciparum gametocytaemia in children in western Kenya. Trop. Med. Int. Health 8:427–430.
    54.
    Bousema J. T. et al.2006. Rapid onset of transmission-reducing antibodies in Javanese migrants exposed to malaria in Papua, Indonesia. Am. J. Trop. Med. Hyg. 74:425–431.
    55.
    Bousema J. T. et al.2006. Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum. J. Infect. Dis. 193:1151–1159.
    56.
    Bousema T. et al.2010. Identification of hot spots of malaria transmission for targeted malaria control. J. Infect. Dis. 201:1764–1774.
    57.
    Bousema T. et al.2010. Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs. Malar. J. 9:136.
    58.
    Bousema T. et al.2010. The dynamics of naturally acquired immune responses to Plasmodium falciparum sexual stage antigens Pfs230 & Pfs48/45 in a low endemic area in Tanzania. PLoS One 5:e14114.
    59.
    Bousema T. et al.2011. Human immune responses that reduce the transmission of Plasmodium falciparum in African populations. Int. J. Parasitol. 41:293–300.
    60.
    Bousema T. et al.2010. Serologic markers for detecting malaria in areas of low endemicity, Somalia, 2008. Emerg. Infect. Dis. 16:392–399.
    61.
    Boyd M. F. and Kitchen S. F..1937. On the infectiousness of patients infected with Plasmodium vivax and Plasmodium falciparum. Am. J. Trop. Med. Hyg. 17:253–262.
    62.
    Boyd M. F., Stratman-Thomas W. K., and Muench H..1935. The occurrence of gametocytes of Plasmodium vivax during the primary attack. Am. J. Trop. Med. Hyg. 16:133–138.
    63.
    Branch O. et al.2005. Clustered local transmission and asymptomatic Plasmodium falciparum and Plasmodium vivax malaria infections in a recently emerged, hypoendemic Peruvian Amazon community. Malar. J. 4:27.
    64.
    Bray R. S., McCrae A. W., and Smalley M. E..1976. Lack of a circadian rhythm in the ability of the gametocytes of Plasmodium falciparum to infect Anopheles gambiae. Int. J. Parasitol. 6:399–401.
    65.
    Brewer G. J. and Zarafonetis C. J..1967. The haemolytic effect of various regimens of primaquine with chloroquine in American Negroes with G6PD deficiency and the lack of an effect of various antimalarial suppressive agents on erythrocyte metabolism. Bull. World Health Organ. 36:303–308.
    66.
    Brockelman C. R.1982. Conditions favoring gametocytogenesis in the continuous culture of Plasmodium falciparum. J. Protozool. 29:454–458.
    67.
    Brooks S. R. and Williamson K. C..2000. Proteolysis of Plasmodium falciparum surface antigen, Pfs230, during gametogenesis. Mol. Biochem. Parasitol. 106:77–82.
    68.
    Bruce M. C., Alano P., Duthie S., and Carter R..1990. Commitment of the malaria parasite Plasmodium falciparum to sexual and asexual development. Parasitology 100:191–200.
    69.
    Bruce M. C., Carter R. N., Nakamura K., Aikawa M., and Carter R..1994. Cellular location and temporal expression of the Plasmodium falciparum sexual stage antigen Pfs16. Mol. Biochem. Parasitol. 65:11–22.
    70.
    Buates S. et al.2010. Development of a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) for clinical detection of Plasmodium falciparum gametocytes. Parasitol. Int. 59:414–420.
    71.
    Buckling A., Crooks L., and Read A..1999. Plasmodium chabaudi: effect of antimalarial drugs on gametocytogenesis. Exp. Parasitol. 93:45–54.
    72.
    Buckling A., Ranford-Cartwright L. C., Miles A., and Read A. F..1999. Chloroquine increases Plasmodium falciparum gametocytogenesis in vitro. Parasitology 118:339–346.
    73.
    Buckling A. and Read A. F..2001. The effect of partial host immunity on the transmission of malaria parasites. Proc. Biol. Sci. 268:2325–2330.
    74.
    Bukirwa H. et al.2006. Artemisinin combination therapies for treatment of uncomplicated malaria in Uganda. PLoS Clin. Trials 1:e7.
    75.
    Burgess R. W. and Bray R. S..1961. The effect of a single dose of primaquine on the gametocytes, gametogony and sporogony of Laverania falciparum. Bull. World Health Organ. 24:451–456.
    76.
    Burkot T. R., Williams J. L., and Schneider I..1984. Infectivity to mosquitoes of Plasmodium falciparum clones grown in vitro from the same isolate. Trans. R. Soc. Trop. Med. Hyg. 78:339–441.
    77.
    Butcher G. A.1997. Antimalarial drugs and the mosquito transmission of Plasmodium. Int. J. Parasitol. 27:975–987.
    78.
    Camarda G. et al.2010. Regulated oligomerisation and molecular interactions of the early gametocyte protein Pfg27 in Plasmodium falciparum sexual differentiation. Int. J. Parasitol. 40:663–673.
    79.
    Canning E. U. and Sinden R. E..1975. Nuclear organisation in gametocytes of Plasmodium and Hepatocystis: a cytochemical study. Z. Parasitenkd. 46:297–299.
    80.
    Carlton J. M. et al.2002. Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature 419:512–519.
    81.
    Carter R. and Chen D. H..1976. Malaria transmission blocked by immunisation with gametes of the malaria parasite. Nature 263:57–60.
    82.
    Carter R. and Graves P. M..1988. Gametocytes, p. 253–306. InWernsdorfer W. H. and McGregor I. A. (ed.), Malaria: principles and practice of malariology. Churchill Livingstone, Edinburgh, United Kingdom.
    83.
    Carter R. et al.1989. Plasmodium falciparum: an abundant stage-specific protein expressed during early gametocyte development. Exp. Parasitol. 69:140–149.
    84.
    Carter R., Graves P. M., Quakyi I. A., and Good M. F..1989. Restricted or absent immune responses in human populations to Plasmodium falciparum gamete antigens that are targets of malaria transmission-blocking antibodies. J. Exp. Med. 169:135–147.
    85.
    Carter R., Mendis K. N., and Roberts D..2000. Spatial targeting of interventions against malaria. Bull. World Health Organ. 78:1401–1411.
    86.
    Carter R. and Miller L. H..1979. Evidence for environmental modulation of gametocytogenesis in Plasmodium falciparum in continuous culture. Bull. World Health Organ. 57(Suppl. 1):37–52.
    87.
    Ceesay S. J. et al.2008. Changes in malaria indices between 1999 and 2007 in The Gambia: a retrospective analysis. Lancet 372:1545–1554.
    88.
    Celada A., Cruchaud A., and Perrin L. H..1983. Phagocytosis of Plasmodium falciparum-parasitized erythrocytes by human polymorphonuclear leukocytes. J. Parasitol. 69:49–53.
    89.
    Chaiyaroj S. C., Thompson J. K., Coppel R. L., and Brown G. V..1994. Gametocytogenesis occurs in Plasmodium falciparum isolates carrying a chromosome 9 deletion. Mol. Biochem. Parasitol. 63:163–165.
    90.
    Cham G. K. et al.2009. Sequential, ordered acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 domains. J. Immunol. 183:3356–3363.
    91.
    Chardome M. and Janssen P. J..1952. Enquête sur l'incidence malarienne par la method dermique dans la region de Lubilash (Congo Belge). Ann. Soc. Belge Med. Trop. 32:209–211.
    92.
    Charoenlarp P., Areekul S., Harinasuta T., and Sirivorasarn P..1972. The haemolytic effect of a single dose of 45 mg of primaquine in G-6-PD deficient Thais. J. Med. Assoc. Thai. 55:631–638.
    93.
    Checchi F. et al.2004. Antimalarial efficacy of sulfadoxine-pyrimethamine, amodiaquine and a combination of chloroquine plus sulfadoxine-pyrimethamine in Bundi Bugyo, western Uganda. Trop. Med. Int. Health 9:445–450.
    94.
    Chen Q., Schlichtherle M., and Wahlgren M..2000. Molecular aspects of severe malaria. Clin. Microbiol. Rev. 13:439–450.
    95.
    Cheru L. et al.2010. The IC(50) of anti-Pfs25 antibody in membrane-feeding assay varies among species. Vaccine 28:4423–4429.
    96.
    Chotivanich K. et al.2006. Transmission-blocking activities of quinine, primaquine, and artesunate. Antimicrob. Agents Chemother. 50:1927–1930.
    97.
    Chowdhury D. R., Angov E., Kariuki T., and Kumar N..2009. A potent malaria transmission blocking vaccine based on codon harmonized full length Pfs48/45 expressed in Escherichia coli. PLoS One 4:e6352.
    98.
    Colbourne M. J.1956. The effect of prolonged examination of bloodfilms on the parasite rate. West Afr. Med. J. 5:26–30.
    99.
    Coleman R. E.1990. Sporontocidal activity of the antimalarial WR-238605 against Plasmodium berghei ANKA in Anopheles stephensi. Am. J. Trop. Med. Hyg. 42:196–205.
    100.
    Coleman R. E., Clavin A. M., and Milhous W. K..1992. Gametocytocidal and sporontocidal activity of antimalarials against Plasmodium berghei ANKA in ICR mice and Anopheles stephensi mosquitoes. Am. J. Trop. Med. Hyg. 46:169–182.
    101.
    Coleman R. E. et al.2004. Infectivity of asymptomatic Plasmodium-infected human populations to Anopheles dirus mosquitoes in western Thailand. J. Med. Entomol. 41:201–208.
    102.
    Conway D. J. et al.2001. Extreme geographical fixation of variation in the Plasmodium falciparum gamete surface protein gene Pfs48/45 compared with microsatellite loci. Mol. Biochem. Parasitol. 115:145–156.
    103.
    Coulibaly B. et al.2009. Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial. PLoS One 4:e5318.
    104.
    Covell G., Coatney G. R., Field J. W., and Singh J..1955. Chemotherapy of malaria. Monogr. Ser. World Health Organ. 27:1–123.
    105.
    Day K. P., Hayward R. E., and Dyer M..1998. The biology of Plasmodium falciparum transmission stages. Parasitology 116S:S95–S109.
    106.
    Day K. P., Hayward R. E., Smith D., and Culvenor J. G..1998. CD36-dependent adhesion and knob expression of the transmission stages of Plasmodium falciparum is stage specific. Mol. Biochem. Parasitol. 93:167–177.
    107.
    Day K. P. et al.1993. Genes necessary for expression of a virulence determinant and for transmission of Plasmodium falciparum are located on a 0.3-megabase region of chromosome 9. Proc. Natl. Acad. Sci. U. S. A. 90:8292–8296.
    108.
    de Koning-Ward T. F. et al.2008. The role of osmiophilic bodies and Pfg377 expression in female gametocyte emergence and mosquito infectivity in the human malaria parasite Plasmodium falciparum. Mol. Microbiol. 67:278–290.
    109.
    De Martin S. et al.2001. Community perceptions of a mass administration of an antimalarial drug combination in The Gambia. Trop. Med. Int. Health 6:442–448.
    110.
    Dern R. J., Beutler E., and Alving A. S..1954. The hemolytic effect of primaquine. II. The natural course of the hemolytic anemia and the mechanism of its self-limited character. J. Lab. Clin. Med. 44:171–176.
    111.
    Diallo M. et al.2008. Evaluation and optimization of membrane feeding compared to direct feeding as an assay for infectivity. Malar. J. 7:248.
    112.
    Dinglasan R. R. et al.2007. Disruption of Plasmodium falciparum development by antibodies against a conserved mosquito midgut antigen. Proc. Natl. Acad. Sci. U. S. A. 104:13461–13466.
    113.
    Dixon M. W., Thompson J., Gardiner D. L., and Trenholme K. R..2008. Sex in Plasmodium: a sign of commitment. Trends Parasitol. 24:168–175.
    114.
    Dondorp A. M. et al.2010. Artemisinin resistance: current status and scenarios for containment. Nat. Rev. Microbiol. 8:272–280.
    115.
    Doolan D. L., Dobano C., and Baird J. K..2009. Acquired immunity to malaria. Clin. Microbiol. Rev. 22:13–36.
    116.
    Dorsey G. et al.2000. Predictors of chloroquine treatment failure in children and adults with falciparum malaria in Kampala, Uganda. Am. J. Trop. Med. Hyg. 62:686–692.
    117.
    Dorsey G. et al.2007. Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial. JAMA 297:2210–2219.
    118.
    Douglas N. M., Anstey N. M., Angus B. J., Nosten F., and Price R. N..2010. Artemisinin combination therapy for vivax malaria. Lancet Infect. Dis. 10:405–416.
    119.
    Dowling M. A. and Shute G. T..1966. A comparative study of thick and thin blood films in the diagnosis of scanty malaria parasitaemia. Bull. World Health Organ. 34:249–267.
    120.
    Drakeley C., Sutherland C., Bousema J. T., Sauerwein R. W., and Targett G. A..2006. The epidemiology of Plasmodium falciparum gametocytes: weapons of mass dispersion. Trends Parasitol. 22:424–430.
    121.
    Drakeley C. J., Akim N. I., Sauerwein R. W., Greenwood B. M., and Targett G. A..2000. Estimates of the infectious reservoir of Plasmodium falciparum malaria in The Gambia and in Tanzania. Trans. R. Soc. Trop. Med. Hyg. 94:472–476.
    122.
    Drakeley C. J. et al.2006. Transmission reducing immunity is inversely related to age in P. falciparum gametocyte carriers. Parasite Immunol. 28:185–190.
    123.
    Drakeley C. J. et al.2005. Altitude-dependent and -independent variations in Plasmodium falciparum prevalence in northeastern Tanzania. J. Infect. Dis. 191:1589–1598.
    124.
    Drakeley C. J. et al.1996. Geographical distribution of a variant epitope of Pfs48/45, a Plasmodium falciparum transmission-blocking vaccine candidate. Mol. Biochem. Parasitol. 81:253–257.
    125.
    Drakeley C. J. et al.2004. Parasite infectivity and immunity to Plasmodium falciparum gametocytes in Gambian children. Parasite Immunol. 26:159–165.
    126.
    Drakeley C. J., Flobbe K., Greenwood B. M., and Targett G. A..2000. Plasmodium falciparum gametocytes in Gambian adults. Ann. Trop. Med. Parasitol. 94:399–401.
    127.
    Drakeley C. J. et al.2004. Addition of artesunate to chloroquine for treatment of Plasmodium falciparum malaria in Gambian children causes a significant but short-lived reduction in infectiousness for mosquitoes. Trop. Med. Int. Health 9:53–61.
    128.
    Drakeley C. J. et al.1998. Transmission-blocking effects of sera from malaria-exposed individuals on Plasmodium falciparum isolates from gametocyte carriers. Parasitology 116:417–423.
    129.
    Drakeley C. J., Secka I., Correa S., Greenwood B. M., and Targett G. A..1999. Host haematological factors influencing the transmission of Plasmodium falciparum gametocytes to Anopheles gambiae s.s. mosquitoes. Trop. Med. Int. Health 4:131–138.
    130.
    Duffy P. E. and Kaslow D. C..1997. A novel malaria protein, Pfs28, and Pfs25 are genetically linked and synergistic as falciparum malaria transmission-blocking vaccines. Infect. Immun. 65:1109–1113.
    131.
    Dunyo S. et al.2006. Gametocytaemia after drug treatment of asymptomatic Plasmodium falciparum. PloS Clin. Trials 1:e20.
    132.
    Dyer M. and Day K..2000. Expression of Plasmodium falciparum trimeric G proteins and their involvement in switching to sexual development. Mol. Biochem. Parasitol. 108:67–78.
    133.
    Dyer M. and Day K. P..2000. Commitment to gametocytogenesis in Plasmodium falciparum. Parasitol. Today 16:102–107.
    134.
    Reference deleted.
    135.
    Reference deleted.
    136.
    Eichner M. et al.2001. Genesis, sequestration and survival of Plasmodium falciparum gametocytes: parameter estimates from fitting a model to malaria therapy data. Trans. R. Soc. Trop. Med. Hyg. 95:497–501.
    137.
    Eksi S. et al.2006. Malaria transmission-blocking antigen, Pfs230, mediates human red blood cell binding to exflagellating male parasites and oocyst production. Mol. Microbiol. 61:991–998.
    138.
    Eksi S. et al.2005. Identification of a subtelomeric gene family expressed during the asexual-sexual stage transition in Plasmodium falciparum. Mol. Biochem. Parasitol. 143:90–99.
    139.
    Eksi S. et al.2002. Targeting and sequestration of truncated Pfs230 in an intraerythrocytic compartment during Plasmodium falciparum gametocytogenesis. Mol. Microbiol. 44:1507–1516.
    140.
    El-Sayed B. et al.2007. A randomized open-label trial of artesunate-sulfadoxine-pyrimethamine with or without primaquine for elimination of sub-microscopic P. falciparum parasitaemia and gametocyte carriage in eastern Sudan. PLoS One 2:e1311.
    141.
    Elzaki S. G., Gadalla N. B. H., Mansour F. A., Mukhtar E. A., and El-Sayed B. B..2006. The impact of clearance of the dry season sub-patent parasitaemia on the prevalence of Plasmodium falciparum in Eastern Sudan, abstr. 1172. Abstr. ICOPA XI Conf., Glasgow, United Kingdom.
    142.
    Enevold A.2006. The influence of genetic innate resistance and acquired immunity on drug treatment outcome of uncomplicated Plasmodium falciparum malaria in Tanzania. Parassitologia 48:547–551.
    143.
    Falk N. et al.2006. Comparison of PCR-RFLP and Genescan-based genotyping for analyzing infection dynamics of Plasmodium falciparum. Am. J. Trop. Med. Hyg. 74:944–950.
    144.
    Fanello C. I. et al.2007. A randomised trial to assess the safety and efficacy of artemether-lumefantrine (Coartem) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwanda. Trans. R. Soc. Trop. Med. Hyg. 101:344–350.
    145.
    Fanning S. L. et al.2003. A glycosylphosphatidylinositol anchor signal sequence enhances the immunogenicity of a DNA vaccine encoding Plasmodium falciparum sexual-stage antigen, Pfs230. Vaccine 21:3228–3235.
    146.
    Faye B. et al.2007. Efficacy and tolerability of four antimalarial combinations in the treatment of uncomplicated Plasmodium falciparum malaria in Senegal. Malar. J. 6:80.
    147.
    Faye B. et al.2010. Efficacy and tolerability of artesunate-amodiaquine (Camoquin Plus) versus artemether-lumefantrine (Coartem) against uncomplicated Plasmodium falciparum malaria: multisite trial in Senegal and Ivory Coast. Trop. Med. Int. Health 15:608–613.
    148.
    Fischer P., Supali T., Wibowo H., Bonow I., and Williams S. A..2000. Detection of DNA of nocturnally periodic Brugia malayi in night and day blood samples by a polymerase chain reaction-ELISA-based method using an internal control DNA. Am. J. Trop. Med. Hyg. 62:291–296.
    149.
    Florens L. et al.2002. A proteomic view of the Plasmodium falciparum life cycle. Nature 419:520–526.
    150.
    French N. et al.2001. Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults. AIDS 15:899–906.
    151.
    Gamage-Mendis A. C., Rajakaruna J., Carter R., and Mendis K. N..1991. Infectious reservoir of Plasmodium vivax and Plasmodium falciparum malaria in an endemic region of Sri Lanka. Am. J. Trop. Med. Hyg. 45:479–487.
    152.
    Gamage-Mendis A. C., Rajakaruna J., Carter R., and Mendis K. N..1992. Transmission blocking immunity to human Plasmodium vivax malaria in an endemic population in Kataragama, Sri Lanka. Parasite Immunol. 14:385–396.
    153.
    Garavito G. et al.2007. Blood schizontocidal activity of methylene blue in combination with antimalarials against Plasmodium falciparum. Parasite 14:135–140.
    154.
    Gardiner D. L. et al.2005. Implication of a Plasmodium falciparum gene in the switch between asexual reproduction and gametocytogenesis. Mol. Biochem. Parasitol. 140:153–160.
    155.
    Gardner M. J. et al.2002. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419:498–511.
    156.
    Gautret P.2001. Plasmodium falciparum gametocyte periodicity. Acta Trop. 78:1–2.
    157.
    Gautret P., Miltgen F., Gantier J. C., Chabaud A. G., and Landau I..1996. Enhanced gametocyte formation by Plasmodium chabaudi in immature erythrocytes: pattern of production, sequestration, and infectivity to mosquitoes. J. Parasitol. 82:900–906.
    158.
    George J. N., Sears D. A., McCurdy P. R., and Conrad M. E..1967. Primaquine sensitivity in Caucasians: hemolytic reactions induced by primaquine in G-6-PD deficient subjects. J. Lab. Clin. Med. 70:80–93.
    159.
    Gillman B. M., Batchelder J., Flaherty P., and Weidanz W. P..2004. Suppression of Plasmodium chabaudi parasitemia is independent of the action of reactive oxygen intermediates and/or nitric oxide. Infect. Immun. 72:6359–6366.
    160.
    Githeko A. K. et al.1992. The reservoir of Plasmodium falciparum malaria in a holoendemic area of western Kenya. Trans. R. Soc. Trop. Med. Hyg. 86:355–358.
    161.
    Githeko A. K. et al.1993. Confirmation that Plasmodium falciparum has aperiodic infectivity to Anopheles gambiae. Med. Vet. Entomol. 7:373–376.
    162.
    Gogtay N. J. et al.2004. Preliminary report of the evaluation of the gametocytocidal action of bulaquine, in adult patients with acute, Plasmodium falciparum malaria. Ann. Trop. Med. Parasitol. 98:525–528.
    163.
    Gogtay N. J. et al.2006. A randomized, parallel study of the safety and efficacy of 45 mg primaquine versus 75 mg bulaquine as gametocytocidal agents in adults with blood schizonticide-responsive uncomplicated falciparum malaria [ISCRTN50134587]. BMC Infect. Dis. 6:16.
    164.
    Gouagna L. C. et al.2010. Genetic variation in human HBB is associated with Plasmodium falciparum transmission. Nat. Genet. 42:328–331.
    165.
    Gouagna L. C. et al.2004. Plasmodium falciparum malaria disease manifestations in humans and transmission to Anopheles gambiae: a field study in Western Kenya. Parasitology 128:235–243.
    166.
    Govere J. M., Durrheim D. N., Mngomezulu N. M., Barnes K., and Sharp B..2003. Infectivity of Plasmodium falciparum gametocytes to Anopheles arabiensis after treatment with sulfadoxine-pyrimethamine. Trans. R. Soc. Trop. Med. Hyg. 97:707–708.
    167.
    Govere J. M. et al.1999. Sulfadoxine-pyrimethamine effectiveness against Plasmodium falciparum malaria in Mpumalanga Province, South Africa. Trans. R. Soc. Trop. Med. Hyg. 93:644.
    168.
    Gozar M. M., Price V. L., and Kaslow D. C..1998. Saccharomyces cerevisiae-secreted fusion proteins Pfs25 and Pfs28 elicit potent Plasmodium falciparum transmission-blocking antibodies in mice. Infect. Immun. 66:59–64.
    169.
    Grande T. et al.2007. A randomised controlled trial to assess the efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Peru. PLoS One 2:e1101.
    170.
    Graves P. M.1980. Studies on the use of a membrane feeding technique for infecting Anopheles gambiae with Plasmodium falciparum. Trans. R. Soc. Trop. Med. Hyg. 74:738–742.
    171.
    Graves P. M. et al.1988. Measurement of malarial infectivity of human populations to mosquitoes in the Madang area, Papua, New Guinea. Parasitology 96:251–263.
    172.
    Graves P. M., Carter R., Burkot T. R., Quakyi I. A., and Kumar N..1988. Antibodies to Plasmodium falciparum gamete surface antigens in Papua New Guinea sera. Parasite Immunol. 10:209–218.
    173.
    Graves P. M., Carter R., and McNeill K. M..1984. Gametocyte production in cloned lines of Plasmodium falciparum. Am. J. Trop. Med. Hyg. 33:1045–1050.
    174.
    Graves P. M. et al.2008. Effectiveness of malaria control during changing climate conditions in Eritrea, 1998–2003. Trop. Med. Int. Health 13:218–228.
    175.
    Greenhouse B. et al.2009. Decreasing efficacy of antimalarial combination therapy in Uganda is explained by decreasing host immunity rather than increasing drug resistance. J. Infect. Dis. 199:758–765.
    176.
    Greenwood B. M. and Armstrong J. R..1991. Comparison of two simple methods for determining malaria parasite density. Trans. R. Soc. Trop. Med. Hyg. 85:186–188.
    177.
    Griffin J. T. et al.2010. Strategies towards Plasmodium falciparum malaria elimination in Africa using currently available tools. PLoS Med. 7:e1000324.
    178.
    Guerra C. A. et al.2008. The limits and intensity of Plasmodium falciparum transmission: implications for malaria control and elimination worldwide. PLoS Med. 5:e38.
    179.
    Guerra C. A. et al.2010. The international limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Negl. Trop. Dis. 4:e774.
    180.
    Guerra C. A., Snow R. W., and Hay S. I..2006. Defining the global spatial limits of malaria transmission in 2005. Adv. Parasitol. 62:157–179.
    181.
    Gwadz R. W.1976. Successful immunization against the sexual stages of Plasmodium gallinaceum. Science 193:1150–1151.
    182.
    Hall N. et al.2005. A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses. Science 307:82–86.
    183.
    Hallett R. L. et al.2006. Chloroquine/sulphadoxine-pyrimethamine for Gambian children with malaria: transmission to mosquitoes of multidrug-resistant Plasmodium falciparum. PLoS Clin. Trials 1:e15.
    184.
    Hallett R. L. et al.2004. Combination therapy counteracts the enhanced transmission of drug-resistant malaria parasites to mosquitoes. Antimicrob. Agents Chemother. 48:3940–3943.
    185.
    Hamour S. et al.2005. Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine-pyrimethamine and artesunate plus amodiaquine combinations. Trans. R. Soc. Trop. Med. Hyg. 99:548–554.
    186.
    Han E. T. et al.2010. Sequence polymorphisms of Plasmodium vivax ookinete surface proteins (Pvs25 and Pvs28) from clinical isolates in Korea. Trop. Med. Int. Health 9:1072–1076.
    187.
    Han E. T. et al.2007. Detection of four Plasmodium species by genus- and species-specific loop-mediated isothermal amplification for clinical diagnosis. J. Clin. Microbiol. 45:2521–2528.
    188.
    Handunnetti S. M. et al.1996. Features of recrudescent chloroquine-resistant Plasmodium falciparum infections confer a survival advantage on parasites and have implications for disease control. Trans. R. Soc. Trop. Med. Hyg. 90:563–567.
    189.
    Hasugian A. R. et al.2007. Dihydroartemisinin-piperaquine versus artesunate-amodiaquine: superior efficacy and posttreatment prophylaxis against multidrug-resistant Plasmodium falciparum and Plasmodium vivax malaria. Clin. Infect. Dis. 44:1067–1074.
    190.
    Hawking F., Wilson M. E., and Gammage K..1971. Evidence for cyclic development and short-lived maturity in the gametocytes of Plasmodium falciparum. Trans. R. Soc. Trop. Med. Hyg. 65:549–559.
    191.
    Hay S. I. et al.2010. Estimating the global clinical burden of Plasmodium falciparum malaria in 2007. PLoS Med. 7:e1000290.
    192.
    Hayward R. E.2000. Plasmodium falciparum phosphoenolpyruvate carboxykinase is developmentally regulated in gametocytes. Mol. Biochem. Parasitol. 107:227–240.
    193.
    Hayward R. E., Tiwari B., Piper K. P., Baruch D. I., and Day K. P..1999. Virulence and transmission success of the malarial parasite Plasmodium falciparum. Proc. Natl. Acad. Sci. U. S. A. 96:4563–4568.
    194.
    Healer J., Graszynski A., and Riley E..1999. Phagocytosis does not play a major role in naturally acquired transmission-blocking immunity to Plasmodium falciparum malaria. Infect. Immun. 67:2334–2339.
    195.
    Healer J., McGuinness D., Carter R., and Riley E..1999. Transmission-blocking immunity to Plasmodium falciparum in malaria-immune individuals is associated with antibodies to the gamete surface protein Pfs230. Parasitology 119:425–433.
    196.
    Healer J. et al.1997. Complement-mediated lysis of Plasmodium falciparum gametes by malaria-immune human sera is associated with antibodies to the gamete surface antigen Pfs230. Infect. Immun. 65:3017–3023.
    197.
    Hill D. R. et al.2006. Primaquine: report from CDC expert meeting on malaria chemoprophylaxis. Am. J. Trop. Med. Hyg. 75:402–415.
    198.
    Hill J., Lines J., and Rowland M..2006. Insecticide-treated nets. Adv. Parasitol. 61:77–128.
    199.
    Hirai M. et al.2008. Male fertility of malaria parasites is determined by GCS1, a plant-type reproduction factor. Curr. Biol. 18:607–613.
    200.
    Hirai M. and Mori T..2010. Fertilization is a novel attacking site for the transmission blocking of malaria parasites. Acta Trop. 114:157–161.
    201.
    Hisaeda H. et al.2000. Antibodies to malaria vaccine candidates Pvs25 and Pvs28 completely block the ability of Plasmodium vivax to infect mosquitoes. Infect. Immun. 68:6618–6623.
    202.
    Hogh B. et al.1998. The differing impact of chloroquine and pyrimethamine/sulfadoxine upon the infectivity of malaria species to the mosquito vector. Am. J. Trop. Med. Hyg. 58:176–182.
    203.
    Huh A. J. et al.2011. Parasitemia characteristics of Plasmodium vivax malaria patients in the Republic of Korea. J. Korean Med. Sci. 26:42–46.
    204.
    Hulden L. and Heliovaara K..2008. Natural relapses in vivax malaria induced by Anopheles mosquitoes. Malar. J. 7:64.
    205.
    Hutagalung R. et al.2005. A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand. Malar. J. 4:46.
    206.
    Ihalamulla R. L. and Mendis K. N..1987. Plasmodium vivax: isolation of mature asexual stages and gametocytes from infected human blood by colloidal silica (Percoll) gradient centrifugation. Trans. R. Soc. Trop. Med. Hyg. 81:25–28.
    207.
    James S. P.1931. Some general results of a study of induced malaria in England. Trans. R. Soc. Trop. Med. Hyg. 24:477–525.
    208.
    Jeffery G. M.1952. The infection of mosquitoes by Plasmodium vivax (Chesson strain) during the early primary parasitemias. Am. J. Trop. Med. Hyg. 1:612–617.
    209.
    Jeffery G. M.1958. Infectivity to mosquitoes of Plasmodium vivax following treatment with chloroquine and other antimalarials. Am. J. Trop. Med. Hyg. 7:207–211.
    210.
    Jeffery G. M. and Eyles D. E..1955. Infectivity to mosquitoes of Plasmodium falciparum as related to gametocyte density and duration of infection. Am. J. Trop. Med. Hyg. 4:781–789.
    211.
    Jeffery G. M., Young M. D., and Eyles D. E..1956. The treatment of Plasmodium falciparum infection with chloroquine, with a note on infectivity to mosquitoes of primaquine- and pyrimethamine-treated cases. Am. J. Hyg. (London) 64:1–11.
    212.
    Kamya M. R. et al.2006. Effect of HIV-1 infection on antimalarial treatment outcomes in Uganda: a population-based study. J. Infect. Dis. 193:9–15.
    213.
    Kamya M. R. et al.2007. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment of malaria: a randomized trial. PLoS Clin. Trials 2:e20.
    214.
    Kaneko A. et al.2000. Malaria eradication on islands. Lancet 356:1560–1564.
    215.
    Kar P. K., Dua V. K., Gupta N. C., Gupta A., and Dash A. P..2009. Plasmodium falciparum gametocytaemia with chloroquine chemotherapy in persistent malaria in an endemic area of India. Indian J. Med. Res. 129:299–304.
    216.
    Karl S. et al.2008. Enhanced detection of gametocytes by magnetic deposition microscopy predicts higher potential for Plasmodium falciparum transmission. Malar. J. 7:66.
    217.
    Karl S., Davis T. M., and St. Pierre T. G..2009. A comparison of the sensitivities of detection of Plasmodium falciparum gametocytes by magnetic fractionation, thick blood film microscopy, and RT-PCR. Malar. J. 8:98.
    218.
    Karunaweera N. D. et al.1992. Tumour necrosis factor-dependent parasite-killing effects during paroxysms in non-immune Plasmodium vivax malaria patients. Clin. Exp. Immunol. 88:499–505.
    219.
    Kaslow D. C. et al.1988. A vaccine candidate from the sexual stage of human malaria that contains EGF-like domains. Nature 333:74–76.
    220.
    Khan S. M. et al.2005. Proteome analysis of separated male and female gametocytes reveals novel sex-specific Plasmodium biology. Cell 121:675–687.
    221.
    Kheir A. et al.2010. Transmission and cross-mating of high-level resistance Plasmodium falciparum dihydrofolate reductase haplotypes in the Gambia. Am. J. Trop. Med. Hyg. 82:535–541.
    222.
    Killick-Kendrick R. and Warren M..1968. Primary exoerythrocytic schizonts of a mammalian Plasmodium as a source of gametocytes. Nature 220:191–192.
    223.
    Klein T. A., Harrison B. A., Grove J. S., Dixon S. V., and Andre R. G..1986. Correlation of survival rates of Anopheles dirus A (Diptera: Culicidae) with different infection densities of Plasmodium cynomolgi. Bull. World Health Organ. 64:901–907.
    224.
    Klein T. A., Lima J. B., and Toda Tang A..1992. Vector incrimination and effects of antimalarial drugs on malaria transmission and control in the Amazon basin of Brazil. Mem. Inst. Oswaldo Cruz 87(Suppl. 3):393–397.
    225.
    Klein T. A., Tada M. S., and Lima J. B..1991. Infection of Anopheles darlingi fed on patients with Plasmodium falciparum before and after treatment with quinine or quinine plus tetracycline. Am. J. Trop. Med. Hyg. 44:604–608.
    226.
    Klein T. A., Tada M. S., Lima J. B., and Katsuragawa T. H..1991. Infection of Anopheles darlingi fed on patients infected with Plasmodium vivax before and during treatment with chloroquine in Costa Marques, Rondonia, Brazil. Am. J. Trop. Med. Hyg. 45:471–478.
    227.
    Kleinschmidt I. et al.2009. Marked increase in child survival after four years of intensive malaria control. Am. J. Trop. Med. Hyg. 80:882–888.
    228.
    Kocken C. H. et al.1993. Cloning and expression of the gene coding for the transmission blocking target antigen Pfs48/45 of Plasmodium falciparum. Mol. Biochem. Parasitol. 61:59–68.
    229.
    Kone A. et al.2010. Sulfadoxine-pyrimethamine impairs Plasmodium falciparum gametocyte infectivity and Anopheles mosquito survival. Int. J. Parasitol. 40:1221–1228.
    230.
    Kongkasuriyachai D. et al.2004. Potent immunogenicity of DNA vaccines encoding Plasmodium vivax transmission-blocking vaccine candidates Pvs25 and Pvs28—evaluation of homologous and heterologous antigen-delivery prime-boost strategy. Vaccine 22:3205–3213.
    231.
    Kubler-Kielb J. et al.2007. Long-lasting and transmission-blocking activity of antibodies to Plasmodium falciparum elicited in mice by protein conjugates of Pfs25. Proc. Natl. Acad. Sci. U. S. A. 104:293–298.
    232.
    Kumar N.1987. Target antigens of malaria transmission blocking immunity exist as a stable membrane bound complex. Parasite Immunol. 9:321–335.
    233.
    Kumar N. and Carter R..1984. Biosynthesis of the target antigens of antibodies blocking transmission of Plasmodium falciparum. Mol. Biochem. Parasitol. 13:333–342.
    234.
    Kumar N. and Carter R..1985. Biosynthesis of two stage-specific membrane proteins during transformation of Plasmodium gallinaceum zygotes into ookinetes. Mol. Biochem. Parasitol. 14:127–139.
    235.
    Kumar N. and Zheng H..1990. Stage-specific gametocytocidal effect in vitro of the antimalaria drug qinghaosu on Plasmodium falciparum. Parasitol. Res. 76:214–218.
    236.
    Kwiatkowski D.1995. Malarial toxins and the regulation of parasite density. Parasitol. Today 11:206–212.
    237.
    Kwiatkowski D. et al.1990. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 336:1201–1204.
    238.
    Lacroix R., Mukabana W. R., Gouagna L. C., and Koella J. C..2005. Malaria infection increases attractiveness of humans to mosquitoes. PLoS Biol. 3:e298.
    239.
    Lasonder E. et al.2002. Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry. Nature 419:537–542.
    240.
    Lawaly Y. R. et al.2010. Heritability of the human infectious reservoir of malaria parasites. PLoS One 5:e11358.
    241.
    Lawpoolsri S. et al.2009. Optimally timing primaquine treatment to reduce Plasmodium falciparum transmission in low endemicity Thai-Myanmar border populations. Malar. J. 8:159.
    242.
    Lefevre G. et al.2001. A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand. Am. J. Trop. Med. Hyg. 64:247–256.
    243.
    Lensen A. et al.1999. Plasmodium falciparum: infectivity of cultured, synchronized gametocytes to mosquitoes. Exp. Parasitol. 91:101–103.
    244.
    Lensen A. et al.1998. Mechanisms that reduce transmission of Plasmodium falciparum malaria in semiimmune and nonimmune persons. J. Infect. Dis. 177:1358–1363.
    245.
    Lensen A. et al.1996. Measurement by membrane feeding of reduction in Plasmodium falciparum transmission induced by endemic sera. Trans. R. Soc. Trop. Med. Hyg. 90:20–22.
    246.
    Lensen A. H., Bolmer-Van de Vegte M., van Gemert G. J., Eling W. M., and Sauerwein R. W..1997. Leukocytes in a Plasmodium falciparum-infected blood meal reduce transmission of malaria to Anopheles mosquitoes. Infect. Immun. 65:3834–3837.
    247.
    Le Roch K. G. et al.2003. Discovery of gene function by expression profiling of the malaria parasite life cycle. Science 301:1503–1508.
    248.
    Leslie T. et al.2007. Sulfadoxine-pyrimethamine, chlorproguanil-dapsone, or chloroquine for the treatment of Plasmodium vivax malaria in Afghanistan and Pakistan: a randomized controlled trial. JAMA 297:2201–2209.
    249.
    Li F., Patra K. P., and Vinetz J. M..2005. An anti-chitinase malaria transmission-blocking single-chain antibody as an effector molecule for creating a Plasmodium falciparum-refractory mosquito. J. Infect. Dis. 192:878–887.
    250.
    Lingnau A., Margos G., Maier W. A., and Seitz H. M..1993. The effects of hormones on the gametocytogenesis of Plasmodium falciparum in vitro. Appl. Parasitol. 34:153–160.
    251.
    Liu Y. et al.2008. The conserved plant sterility gene HAP2 functions after attachment of fusogenic membranes in Chlamydomonas and Plasmodium gametes. Genes Dev. 22:1051–1068.
    252.
    Lobo C. A., Dhar R., and Kumar N..1999. Immunization of mice with DNA-based Pfs25 elicits potent malaria transmission-blocking antibodies. Infect. Immun. 67:1688–1693.
    253.
    Lobo C. A., Fujioka H., Aikawa M., and Kumar N..1999. Disruption of the Pfg27 locus by homologous recombination leads to loss of the sexual phenotype in P. falciparum. Mol. Cell 3:793–798.
    254.
    Luxemburger C. et al.1994. Permethrin-impregnated bed nets for the prevention of malaria in schoolchildren on the Thai-Burmese border. Trans. R. Soc. Trop. Med. Hyg. 88:155–159.
    255.
    Mabunda S., Casimiro S., Quinto L., and Alonso P..2008. A country-wide malaria survey in Mozambique. I. Plasmodium falciparum infection in children in different epidemiological settings. Malar. J. 7:216.
    256.
    Maeno Y. et al.2008. A dried blood sample on filter paper is suitable for detecting Plasmodium falciparum gametocytes by reverse transcription polymerase chain reaction. Acta Trop. 107:121–127.
    257.
    Magesa S. M., Mdira Y. K., Akida J. A., Bygbjerg I. C., and Jakobsen P. H..2000. Observations on the periodicity of Plasmodium falciparum gametocytes in natural human infections. Acta Trop. 76:239–246.
    258.
    Maier W. A., Becker-Feldman H., and Seitz H. M..1987. Pathology of malaria-infected mosquitoes. Parasitol. Today 3:216–218.
    259.
    Mair G. R. et al.2006. Regulation of sexual development of Plasmodium by translational repression. Science 313:667–669.
    260.
    Mair G. R. et al.2010. Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development. PLoS Pathog. 6:e1000767.
    261.
    Males S., Gaye O., and Garcia A..2008. Long-term asymptomatic carriage of Plasmodium falciparum protects from malaria attacks: a prospective study among Senegalese children. Clin. Infect. Dis. 46:516–522.
    262.
    Malkin E. M. et al.2005. Phase 1 vaccine trial of Pvs25H: a transmission blocking vaccine for Plasmodium vivax malaria. Vaccine 23:3131–3138.
    263.
    Marangi M. et al.2009. Prevalence of Plasmodium spp. in malaria asymptomatic African migrants assessed by nucleic acid sequence based amplification. Malar. J. 8:12.
    264.
    Marques P. X. et al.2005. Plasmodium species mixed infections in two areas of Manhica District, Mozambique. Int. J. Biol. Sci. 1:96–102.
    265.
    Maswoswe S. M., Peters W., and Warhurst D. C..1985. Corticosteroid stimulation of the growth of Plasmodium falciparum gametocytes in vitro. Ann. Trop. Med. Parasitol. 79:607–616.
    266.
    Mayxay M. et al.2004. Randomized comparison of chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in the Lao People's Democratic Republic. Clin. Infect. Dis. 39:1139–1147.
    267.
    McGilvray I. D., Serghides L., Kapus A., Rotstein O. D., and Kain K. C..2000. Nonopsonic monocyte/macrophage phagocytosis of Plasmodium falciparum-parasitized erythrocytes: a role for CD36 in malarial clearance. Blood 96:3231–3240.
    268.
    McKenzie F. E., Jeffery G. M., and Collins W. E..2007. Gametocytemia and fever in human malaria infections. J. Parasitol. 93:627–633.
    269.
    McKenzie F. E., Jeffery G. M., and Collins W. E..2002. Plasmodium malariae infection boosts Plasmodium falciparum gametocyte production. Am. J. Trop. Med. Hyg. 67:411–414.
    270.
    McKenzie F. E., Jeffery G. M., and Collins W. E..2002. Plasmodium vivax blood-stage dynamics. J. Parasitol. 88:521–535.
    271.
    McKenzie F. E. et al.2006. Gametocytemia in Plasmodium vivax and Plasmodium falciparum infections. J. Parasitol. 92:1281–1285.
    272.
    McMahon J. E., Marshall T. F., Vaughan J. P., and Kolstrup N..1979. Tanzania Filariasis Project: a provocative day test with diethylcarbamazine for the detection of microfilariae of nocturnally periodic Wuchereria bancrofti in the blood. Bull. World Health Organ. 57:759–765.
    273.
    McRobert L. et al.2004. Distinct trafficking and localization of STEVOR proteins in three stages of the Plasmodium falciparum life cycle. Infect. Immun. 72:6597–6602.
    274.
    Mendez F. et al.2007. Selection of antifolate-resistant Plasmodium falciparum by sulfadoxine-pyrimethamine treatment and infectivity to Anopheles mosquitoes. Am. J. Trop. Med. Hyg. 77:438–443.
    275.
    Mendez F. et al.2002. Determinants of treatment response to sulfadoxine-pyrimethamine and subsequent transmission potential in falciparum malaria. Am. J. Epidemiol. 156:230–238.
    276.
    Mendis K. et al.2009. From malaria control to eradication: the WHO perspective. Trop. Med. Int. Health 14:802–809.
    277.
    Menegon M. et al.2000. Genotyping of Plasmodium falciparum gametocytes by reverse transcriptase polymerase chain reaction. Mol. Biochem. Parasitol. 111:153–161.
    278.
    Menendez C., D'Alessandro U., and ter Kuile F. O..2007. Reducing the burden of malaria in pregnancy by preventive strategies. Lancet Infect. Dis. 7:126–135.
    279.
    Mens P. F. et al.2008. A randomized trial to monitor the efficacy and effectiveness by QT-NASBA of artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment and transmission control of uncomplicated Plasmodium falciparum malaria in western Kenya. Malar. J. 7:237.
    280.
    Meszoely C. A., Erbe E. F., Steere R. L., Trosper J., and Beaudoin R. L..1987. Plasmodium falciparum: freeze-fracture of the gametocyte pellicular complex. Exp. Parasitol. 64:300–309.
    281.
    Metselaar D.1960. Relative increase in the prevalence of Plasmodium falciparum some years after the beginning of a house-spraying campaign in Netherlands New Guinea. Trans. R. Soc. Trop. Med. Hyg. 54:523–528.
    282.
    Michel K. and Kafatos F. C..2005. Mosquito immunity against Plasmodium. Insect Biochem. Mol. Biol. 35:677–689.
    283.
    Miller M. J.1958. Observations on the natural history of malaria in the semi-resistant West African. Trans. R. Soc. Trop. Med. Hyg. 52:152–168.
    284.
    Mitri C., Thiery I., Bourgouin C., and Paul R. E..2009. Density-dependent impact of the human malaria parasite Plasmodium falciparum gametocyte sex ratio on mosquito infection rates. Proc. Biol. Sci. 276:3721–3726.
    285.
    Miyata T. et al.2010. Plasmodium vivax ookinete surface protein Pvs25 linked to cholera toxin B subunit induces potent transmission-blocking immunity by intranasal as well as subcutaneous immunization. Infect. Immun. 78:3773–3782.
    286.
    Mlambo G., Vasquez Y., LeBlanc R., Sullivan D., and Kumar N..2008. A filter paper method for the detection of Plasmodium falciparum gametocytes by reverse transcription polymerase chain reaction. Am. J. Trop. Med. Hyg. 78:114–116.
    287.
    Mockenhaupt F. P. et al.2005. A randomised, placebo-controlled, and double-blind trial on sulfadoxine-pyrimethamine alone or combined with artesunate or amodiaquine in uncomplicated malaria. Trop. Med. Int. Health 10:512–520.
    288.
    Mockenhaupt F. P. et al.2005. Plasmodium falciparum dhfr but not dhps mutations associated with sulphadoxine-pyrimethamine treatment failure and gametocyte carriage in northern Ghana. Trop. Med. Int. Health 10:901–908.
    289.
    Molineaux L. and Gramiccia G..1980. The Garki Project. Research on the epidemiology and control of malaria in the Sudan savannah of West Africa. World Health Organization, Geneva, Switzerland.
    290.
    Molineaux L., Storey J., Cohen J. E., and Thomas A..1980. A longitudinal study of human malaria in the West African savanna in the absence of control measures: relationships between different Plasmodium species, in particular P. falciparum and P. malariae. Am. J. Trop. Med. Hyg. 29:725–737.
    291.
    Mons B.1986. Intra erythrocytic differentiation of Plasmodium berghei. Acta Leiden. 54:1–124.
    292.
    Moody A.2002. Rapid diagnostic tests for malaria parasites. Clin. Microbiol. Rev. 15:66–78.
    293.
    Moonen B. et al.2010. Operational strategies to achieve and maintain malaria elimination. Lancet 376:1592–1603.
    294.
    Mori T., Kuroiwa H., Higashiyama T., and Kuroiwa T..2006. Generative cell specific 1 is essential for angiosperm fertilization. Nat. Cell Biol. 8:64–71.
    295.
    Motard A. et al.1995. Immunization with the malaria heat shock like protein hsp70-1 enhances transmission to the mosquito. Int. Immunol. 7:147–150.
    296.
    Mueller I. et al.2009. Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infect. Dis. 9:555–566.
    297.
    Muirhead-Thomson R. C.1954. Factors determining the true reservoir of infection of Plasmodium falciparum and Wuchereria bancrofti in a West African village. Trans. R. Soc. Trop. Med. Hyg. 48:208–225.
    298.
    Muirhead-Thomson R. C.1957. The malarial infectivity of an African village population to mosquitoes (Anopheles gambiae); a random xenodiagnostic survey. Am. J. Trop. Med. Hyg. 6:971–979.
    299.
    Muirhead-Thomson R. C.1998. Where do most mosquitoes acquire their malarial (Plasmodium falciparum) infection? From adults or from children? Ann. Trop. Med. Parasitol. 92:891–893.
    300.
    Mulder B. et al.1999. Plasmodium falciparum: membrane feeding assays and competition ELISAs for the measurement of transmission reduction in sera from Cameroon. Exp. Parasitol. 92:81–86.
    301.
    Mulder B., van der Ligt W., Sauerwein R., and Verhave J. P..1998. Detection of Plasmodium falciparum gametocytes with the OBC test and Giemsa-stained thick blood films for malaria transmission studies in Cameroon. Trans. R. Soc. Trop. Med. Hyg. 92:395–396.
    302.
    Muturi E. J. et al.2006. Concomitant infections of Plasmodium falciparum and Wuchereria bancrofti on the Kenyan coast. Filaria J. 5:8.
    303.
    Mwangi T. W., Ross A., Snow R. W., and Marsh K..2005. Case definitions of clinical malaria under different transmission conditions in Kilifi District, Kenya. J. Infect. Dis. 191:1932–1939.
    304.
    Nacher M.2004. Does the shape of Plasmodium falciparum gametocytes have a function? Med. Hypotheses 62:618–619.
    305.
    Nacher M.2002. Malarial anaemia: a crossroad? Med. Hypotheses 59:363–365.
    306.
    Nacher M. et al.2004. Seasonal variation in hyperparasitaemia and gametocyte carriage in patients with Plasmodium falciparum malaria on the Thai-Burmese border. Trans. R. Soc. Trop. Med. Hyg. 98:322–328.
    307.
    Nacher M. et al.2004. Seasonal fluctuations in the carriage of Plasmodium vivax gametocytes in Thailand. Ann. Trop. Med. Parasitol. 98:115–120.
    308.
    Nacher M. et al.2004. Comparison of artesunate and chloroquine activities against Plasmodium vivax gametocytes. Antimicrob. Agents Chemother. 48:2751–2752.
    309.
    Nacher M. et al.2004. Risk factors for Plasmodium vivax gametocyte carriage in Thailand. Am. J. Trop. Med. Hyg. 71:693–695.
    310.
    Nacher M. et al.2002. Decreased hemoglobin concentrations, hyperparasitemia, and severe malaria are associated with increased Plasmodium falciparum gametocyte carriage. J. Parasitol. 88:97–101.
    311.
    Naotunne T. D., Rathnayake K. D., Jayasinghe A., Carter R., and Mendis K. N..1990. Plasmodium cynomolgi: serum-mediated blocking and enhancement of infectivity to mosquitoes during infections in the natural host, Macaca sinica. Exp. Parasitol. 71:305–313.
    312.
    Naotunne T. S. et al.1991. Cytokines kill malaria parasites during infection crisis: extracellular complementary factors are essential. J. Exp. Med. 173:523–529.
    313.
    Naotunne T. S., Karunaweera N. D., Mendis K. N., and Carter R..1993. Cytokine-mediated inactivation of malarial gametocytes is dependent on the presence of white blood cells and involves reactive nitrogen intermediates. Immunology 78:555–562.
    314.
    Nassir E. et al.2005. Impact of genetic complexity on longevity and gametocytogenesis of Plasmodium falciparum during the dry and transmission-free season of eastern Sudan. Int. J. Parasitol. 35:49–55.
    315.
    Newell E. D.1997. Comparison of the use of skin scarification and skin biopsies to determine the prevalence and intensity of Onchocerca volvulus infection. Ann. Trop. Med. Parasitol. 91:633–642.
    316.
    Nkhoma E. T., Poole C., Vannappagari V., Hall S. A., and Beutler E..2009. The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Blood Cells Mol. Dis. 42:267–278.
    317.
    Noden B. H. et al.1994. Plasmodium falciparum: the population structure of mature gametocyte cultures has little effect on their innate fertility. Acta Trop. 58:13–19.
    318.
    Nosten F. et al.2000. Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study. Lancet 356:297–302.
    319.
    Nwakanma D. et al.2008. High gametocyte complexity and mosquito infectivity of Plasmodium falciparum in the Gambia. Int. J. Parasitol. 38:219–227.
    320.
    Oesterholt M. J. et al.2009. Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya. PLoS One 4:e4364.
    321.
    Oesterholt M. J. et al.2006. Spatial and temporal variation in malaria transmission in a low endemicity area in northern Tanzania. Malar. J. 5:98.
    322.
    Oh S. S., Chishti A. H., Palek J., and Liu S. C..1997. Erythrocyte membrane alterations in Plasmodium falciparum malaria sequestration. Curr. Opin. Hematol. 4:148–154.
    323.
    Okell L. C., Drakeley C. J., Bousema T., Whitty C. J., and Ghani A. C..2008. Modelling the impact of artemisinin combination therapy and long-acting treatments on malaria transmission intensity. PLoS Med. 5:e226.
    324.
    Okell L. C., Drakeley C. J., Ghani A. C., Bousema T., and Sutherland C. J..2008. Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials. Malar. J. 7:125.
    325.
    Okell L. C., Ghani A. C., Lyons E., and Drakeley C. J..2009. Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. J. Infect. Dis. 200:1509–1517.
    326.
    Okell L. C.. The potential contribution of mass treatment to the control of Plasmodium falciparum malaria. PLoS One, in press.
    327.
    Olliaro P., Taylor W. R., and Rigal J..2001. Controlling malaria: challenges and solutions. Trop. Med. Int. Health 6:922–927.
    328.
    O'Meara W. P. et al.2008. Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, Kenya. Lancet 372:1555–1562.
    329.
    O'Meara W. P., Mangeni J. N., Steketee R., and Greenwood B..2010. Changes in the burden of malaria in sub-Saharan Africa. Lancet Infect. Dis. 10:545–555.
    330.
    Ono T. and Nakabayashi T..1990. Gametocytogenesis induction by ammonium compounds in cultured Plasmodium falciparum. Int. J. Parasitol. 20:615–618.
    331.
    Ono T., Nakai T., and Nakabayashi T..1986. Induction of gametocytogenesis in Plasmodium falciparum by the culture supernatant of hybridoma cells producing anti-P. falciparum antibody. Biken J. 29:77–81.
    332.
    Ono T., Ohnishi Y., Nagamune K., and Kano M..1993. Gametocytogenesis induction by Berenil in cultured Plasmodium falciparum. Exp. Parasitol. 77:74–78.
    333.
    Osorio L., Ferro B. E., and Castillo C. M..2002. Effects of chloroquine and sulfadoxine/pyrimethamine on gametocytes in patients with uncomplicated Plasmodium falciparum malaria in Colombia. Mem. Inst. Oswaldo Cruz 97:1221–1223.
    334.
    Ouedraogo A. L. et al.2010. The plasticity of Plasmodium falciparum gametocytaemia in relation to age in Burkina Faso. Malar. J. 9:281.
    335.
    Ouedraogo A. L. et al.2009. Substantial contribution of submicroscopical Plasmodium falciparum gametocyte carriage to the infectious reservoir in an area of seasonal transmission. PLoS One 4:e8410.
    336.
    Ouedraogo A. L. et al.2008. Seasonal patterns of Plasmodium falciparum gametocyte prevalence and density in a rural population of Burkina Faso. Acta Trop. 105:28–34.
    337.
    Ouedraogo A. L. et al.2007. Age-dependent distribution of Plasmodium falciparum gametocytes quantified by Pfs25 real-time QT-NASBA in a cross-sectional study in Burkina Faso. Am. J. Trop. Med. Hyg. 76:626–630.
    338.
    Outchkourov N. S. et al.2008. Correctly folded Pfs48/45 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in mice. Proc. Natl. Acad. Sci. U. S. A. 105:4301–4305.
    339.
    Owusu-Agyei S. et al.2008. An open label, randomised trial of artesunate+amodiaquine, artesunate+chlorproguanil-dapsone and artemether-lumefantrine for the treatment of uncomplicated malaria. PLoS One 3:e2530.
    340.
    Paganotti G. M. et al.2006. Genetic complexity and gametocyte production of Plasmodium falciparum in Fulani and Mossi communities in Burkina Faso. Parasitology 132:607–614.
    341.
    Panichakul T. et al.2007. Production of erythropoietic cells in vitro for continuous culture of Plasmodium vivax. Int. J. Parasitol. 37:1551–1557.
    342.
    Paton M. G. et al.1993. Structure and expression of a post-transcriptionally regulated malaria gene encoding a surface protein from the sexual stages of Plasmodium berghei. Mol. Biochem. Parasitol. 59:263–275.
    343.
    Paul R. E., Brey P. T., and Robert V..2002. Plasmodium sex determination and transmission to mosquitoes. Trends Parasitol. 18:32–38.
    344.
    Paul R. E., Coulson T. N., Raibaud A., and Brey P. T..2000. Sex determination in malaria parasites. Science 287:128–131.
    345.
    Paul R. E., Diallo M., and Brey P. T..2004. Mosquitoes and transmission of malaria parasites—not just vectors. Malar. J. 3:39.
    346.
    Paul R. E., Doerig C., and Brey P. T..2000. Erythropoiesis and molecular mechanisms for sexual determination in malaria parasites. IUBMB Life 49:245–248.
    347.
    Paul R. E. et al.1995. Mating patterns in malaria parasite populations of Papua New Guinea. Science 269:1709–1711.
    348.
    Peatey C. L. et al.2009. Effect of antimalarial drugs on Plasmodium falciparum gametocytes. J. Infect. Dis. 200:1518–1521.
    349.
    Peiris J. S. et al.1988. Monoclonal and polyclonal antibodies both block and enhance transmission of human Plasmodium vivax malaria. Am. J. Trop. Med. Hyg. 39:26–32.
    350.
    Pethleart A. et al.2004. Infectious reservoir of Plasmodium infection in Mae Hong Son Province, north-west Thailand. Malar. J. 3:34.
    351.
    Petter M., Bonow I., and Klinkert M. Q..2008. Diverse expression patterns of subgroups of the rif multigene family during Plasmodium falciparum gametocytogenesis. PLoS One 3:e3779.
    352.
    Pichon G., Awono-Ambene H. P., and Robert V..2000. High heterogeneity in the number of Plasmodium falciparum gametocytes in the bloodmeal of mosquitoes fed on the same host. Parasitology 121:115–120.
    353.
    Piola P. et al.2005. Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial. Lancet 365:1467–1473.
    354.
    Piper K. P., Hayward R. E., Cox M. J., and Day K. P..1999. Malaria transmission and naturally acquired immunity to PfEMP-1. Infect. Immun. 67:6369–6374.
    355.
    Ponnudurai T. et al.1989. Infectivity of cultured Plasmodium falciparum gametocytes to mosquitoes. Parasitology 98:165–173.
    356.
    Ponnudurai T., Van Gemert G. J., Bensink T., Lensen A. H., and Meuwissen J. H..1987. Transmission blockade of Plasmodium falciparum: its variability with gametocyte numbers and concentration of antibody. Trans. R. Soc. Trop. Med. Hyg. 81:491–493.
    357.
    Port G. R., Boreham P. F. L., and Bryan J. H..1980. The relationship of host size to feeding by mosquitoes of the Anopheles gambiae Giles complex (Diptera: Culicidae). Bull. Entomol. Res. 70:133–144.
    358.
    Pradel G.2007. Proteins of the malaria parasite sexual stages: expression, function and potential for transmission blocking strategies. Parasitology 134:1911–1929.
    359.
    Premawansa S. et al.1994. Plasmodium falciparum malaria transmission-blocking immunity under conditions of low endemicity as in Sri Lanka. Parasite Immunol. 16:35–42.
    360.
    Price R. et al.1999. Risk factors for gametocyte carriage in uncomplicated falciparum malaria. Am. J. Trop. Med. Hyg. 60:1019–1023.
    361.
    Price R. N. et al.1996. Effects of artemisinin derivatives on malaria transmissibility. Lancet 347:1654–1658.
    362.
    Pukrittayakamee S. et al.2000. Therapeutic responses to different antimalarial drugs in vivax malaria. Antimicrob. Agents Chemother. 44:1680–1685.
    363.
    Pukrittayakamee S. et al.2004. Activities of artesunate and primaquine against asexual- and sexual-stage parasites in falciparum malaria. Antimicrob. Agents Chemother. 48:1329–1334.
    364.
    Pukrittayakamee S. et al.2001. Therapeutic responses to antibacterial drugs in vivax malaria. Trans. R. Soc. Trop. Med. Hyg. 95:524–528.
    365.
    Pukrittayakamee S. et al.2008. Effects of different antimalarial drugs on gametocyte carriage in P. vivax malaria. Am. J. Trop. Med. Hyg. 79:378–384.
    366.
    Pukrittayakamee S., Vanijanonta S., Chantra A., Clemens R., and White N. J..1994. Blood stage antimalarial efficacy of primaquine in Plasmodium vivax malaria. J. Infect. Dis. 169:932–935.
    367.
    Puta C. and Manyando C..1997. Enhanced gametocyte production in Fansidar-treated Plasmodium falciparum malaria patients: implications for malaria transmission control programmes. Trop. Med. Int. Health 2:227–229.
    368.
    Qiu Y. T., Smallegange R. C., Van Loon J. J., ter Braak C. J., and Takken W..2006. Interindividual variation in the attractiveness of human odours to the malaria mosquito Anopheles gambiae s.s. Med. Vet. Entomol. 20:280–287.
    369.
    Quakyi I. A. et al.1987. The 230-kDa gamete surface protein of Plasmodium falciparum is also a target for transmission-blocking antibodies. J. Immunol. 139:4213–4217.
    370.
    Raabe A. C., Billker O., Vial H. J., and Wengelnik K..2009. Quantitative assessment of DNA replication to monitor microgametogenesis in Plasmodium berghei. Mol. Biochem. Parasitol. 168:172–176.
    371.
    Ramharter M. et al.2002. In vitro activity of tafenoquine alone and in combination with artemisinin against Plasmodium falciparum. Am. J. Trop. Med. Hyg. 67:39–43.
    372.
    Ranawaka M. B., Munesinghe Y. D., de Silva D. M., Carter R., and Mendis K. N..1988. Boosting of transmission-blocking immunity during natural Plasmodium vivax infections in humans depends upon frequent reinfection. Infect. Immun. 56:1820–1824.
    373.
    Ranford-Cartwright L. C., Balfe P., Carter R., and Walliker D..1993. Frequency of cross-fertilization in the human malaria parasite Plasmodium falciparum. Parasitology 107:11–18.
    374.
    Ratcliff A. et al.2007. Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison. Lancet 369:757–765.
    375.
    Ratcliff A. et al.2007. Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to chloroquine and sulfadoxine-pyrimethamine in southern Papua, Indonesia. Trans. R. Soc. Trop. Med. Hyg. 101:351–359.
    376.
    Read D. et al.1994. Transmission-blocking antibodies against multiple, non-variant target epitopes of the Plasmodium falciparum gamete surface antigen Pfs230 are all complement-fixing. Parasite Immunol. 16:511–519.
    377.
    Read L. K. and Mikkelsen R. B..1991. Comparison of adenylate cyclase and cAMP-dependent protein kinase in gametocytogenic and nongametocytogenic clones of Plasmodium falciparum. J. Parasitol. 77:346–352.
    378.
    Reece S. E., Drew D. R., and Gardner A..2008. Sex ratio adjustment and kin discrimination in malaria parasites. Nature 453:609–614.
    379.
    Reece S. E., Duncan A. B., West S. A., and Read A. F..2005. Host cell preference and variable transmission strategies in malaria parasites. Proc. Biol. Sci. 272:511–517.
    380.
    Reece S. E., Duncan A. B., West S. A., and Read A. F..2003. Sex ratios in the rodent malaria parasite, Plasmodium chabaudi. Parasitology 127:419–425.
    381.
    Reeve P. A., Toaliu H., Kaneko A., Hall J. J., and Ganczakowski M..1992. Acute intravascular haemolysis in Vanuatu following a single dose of primaquine in individuals with glucose-6-phosphate dehydrogenase deficiency. J. Trop. Med. Hyg. 95:349–351.
    382.
    Rener J., Graves P. M., Carter R., Williams J. L., and Burkot T. R..1983. Target antigens of transmission-blocking immunity on gametes of Plasmodium falciparum. J. Exp. Med. 158:976–981.
    383.
    Robert V., Awono-Ambene H. P., Le Hesran J. Y., and Trape J. F..2000. Gametocytemia and infectivity to mosquitoes of patients with uncomplicated Plasmodium falciparum malaria attacks treated with chloroquine or sulfadoxine plus pyrimethamine. Am. J. Trop. Med. Hyg. 62:210–216.
    384.
    Robert V., Molez J. F., and Trape J. F..1996. Short report: gametocytes, chloroquine pressure, and the relative parasite survival advantage of resistant strains of falciparum malaria in west Africa. Am. J. Trop. Med. Hyg. 55:350–351.
    385.
    Robert V. et al.1996. Effect of gametocyte sex ratio on infectivity of Plasmodium falciparum to Anopheles gambiae. Trans. R. Soc. Trop. Med. Hyg. 90:621–624.
    386.
    Robert V., Sokhna C. S., Rogier C., Ariey F., and Trape J. F..2003. Sex ratio of Plasmodium falciparum gametocytes in inhabitants of Dielmo, Senegal. Parasitology 127:1–8.
    387.
    Robert V. et al.1996. Effect of the sickle cell trait status of gametocyte carriers of Plasmodium falciparum on infectivity to anophelines. Am. J. Trop. Med. Hyg. 54:111–113.
    388.
    Roeffen W. et al.1995. Plasmodium falciparum: a comparison of the activity of Pfs230-specific antibodies in an assay of transmission-blocking immunity and specific competition ELISAs. Exp. Parasitol. 80:15–26.
    389.
    Roeffen W. et al.1996. Association between anti-Pfs48/45 reactivity and P. falciparum transmission-blocking activity in sera from Cameroon. Parasite Immunol. 18:103–109.
    390.
    Rogers N. J., Hall B. S., Obiero J., Targett G. A., and Sutherland C. J..2000. A model for sequestration of the transmission stages of Plasmodium falciparum: adhesion of gametocyte-infected erythrocytes to human bone marrow cells. Infect. Immun. 68:3455–3462.
    391.
    Rupp I.. Malaria parasites form filamentous cell-to-cell connections during reproduction in the mosquito midgut. Cell Res., in press.
    392.
    Saeed M. et al.2008. Plasmodium falciparum antigens on the surface of the gametocyte-infected erythrocyte. PLoS One 3:e2280.
    393.
    Sattabongkot J. et al.2003. Comparison of artificial membrane feeding with direct skin feeding to estimate the infectiousness of Plasmodium vivax gametocyte carriers to mosquitoes. Am. J. Trop. Med. Hyg. 69:529–535.
    394.
    Sattabongkot J., Maneechai N., and Rosenberg R..1991. Plasmodium vivax: gametocyte infectivity of naturally infected Thai adults. Parasitology 102:27–31.
    395.
    Sattabongkot J. et al.2003. Blocking of transmission to mosquitoes by antibody to Plasmodium vivax malaria vaccine candidates Pvs25 and Pvs28 despite antigenic polymorphism in field isolates. Am. J. Trop. Med. Hyg. 69:536–541.
    396.
    Sattler M. A. et al.2005. Habitat characterization and spatial distribution of Anopheles sp. mosquito larvae in Dar es Salaam (Tanzania) during an extended dry period. Malar. J. 4:4.
    397.
    Sauerwein R. W.2007. Malaria transmission-blocking vaccines: the bonus of effective malaria control. Microbes Infect. 9:792–795.
    398.
    Saul A.1993. Minimal efficacy requirements for malarial vaccines to significantly lower transmission in epidemic or seasonal malaria. Acta Trop. 52:283–296.
    399.
    Saul A.2007. Mosquito stage, transmission blocking vaccines for malaria. Curr. Opin. Infect. Dis. 20:476–481.
    400.
    Schall J. J.2000. Transmission success of the malaria parasite Plasmodium mexicanum into its vector: role of gametocyte density and sex ratio. Parasitology 121:575–580.
    401.
    Schlesinger P. H., Krogstad D. J., and Herwaldt B. L..1988. Antimalarial agents: mechanisms of action. Antimicrob. Agents Chemother. 32:793–798.
    402.
    Schneider P. et al.2007. Submicroscopic Plasmodium falciparum gametocyte densities frequently result in mosquito infection. Am. J. Trop. Med. Hyg. 76:470–474.
    403.
    Schneider P. et al.2006. (Sub)microscopic Plasmodium falciparum gametocytaemia in Kenyan children after treatment with sulphadoxine-pyrimethamine monotherapy or in combination with artesunate. Int. J. Parasitol. 36:403–408.
    404.
    Schneider P. et al.2004. Quantification of Plasmodium falciparum gametocytes in differential stages of development by quantitative nucleic acid sequence-based amplification. Mol. Biochem. Parasitol. 137:35–41.
    405.
    Schoone G. J., Oskam L., Kroon N. C., Schallig H. D., and Omar S. A..2000. Detection and quantification of Plasmodium falciparum in blood samples using quantitative nucleic acid sequence-based amplification. J. Clin. Microbiol. 38:4072–4075.
    406.
    Schulemann W.1932. Synthetic anti-malarial preparations. Proc. R. Soc. Med. 25:897–905.
    407.
    Schwank S.2010. Ph.D. thesis. University of London, London, United Kingdom.
    408.
    Sharma A., Sharma I., Kogkasuriyachai D., and Kumar N..2003. Structure of a gametocyte protein essential for sexual development in Plasmodium falciparum. Nat. Struct. Biol. 10:197–203.
    409.
    Sharma Y. D.1991. Knobs, knob proteins and cytoadherence in falciparum malaria. Int. J. Biochem. 23:775–789.
    410.
    Sharp S.2007. Ph.D. thesis. University of London, London, United Kingdom.
    411.
    Sharp S. et al.2006. Programmed transcription of the var gene family, but not of stevor, in Plasmodium falciparum gametocytes. Eukaryot. Cell 5:1206–1214.
    412.
    Shekalaghe S. et al.2007. Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine- pyrimethamine and artesunate. PLoS One 2:e1023.
    413.
    Shekalaghe S. A. et al.2007. Submicroscopic Plasmodium falciparum gametocyte carriage is common in an area of low and seasonal transmission in Tanzania. Trop. Med. Int. Health 12:547–553.
    414.
    Shekalaghe S. A. et al.2010. In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A−) individuals. Antimicrob. Agents Chemother. 54:1762–1768.
    415.
    Shutler D., Reece S. E., Mullie A., Billingsley P. F., and Read A. F..2005. Rodent malaria parasites Plasmodium chabaudi and P. vinckei do not increase their rates of gametocytogenesis in response to mosquito probing. Proc. Biol. Sci. 272:2397–2402.
    416.
    Silvestrini F., Alano P., and Williams J. L..2000. Commitment to the production of male and female gametocytes in the human malaria parasite Plasmodium falciparum. Parasitology 121:465–471.
    417.
    Silvestrini F. et al.2005. Genome-wide identification of genes upregulated at the onset of gametocytogenesis in Plasmodium falciparum. Mol. Biochem. Parasitol. 143:100–110.
    418.
    Simonetti A. B., Billingsley P. F., Winger L. A., and Sinden R. E..1993. Kinetics of expression of two major Plasmodium berghei antigens in the mosquito vector, Anopheles stephensi. J. Eukaryot. Microbiol. 40:569–576.
    419.
    Sinclair D., Zani B., Donegan S., Olliaro P., and Garner P..2009. Artemisinin-based combination therapy for treating uncomplicated malaria. Cochrane Database Syst. Rev. 2009:CD007483.
    420.
    Sinden R. E.1983. The cell biology of sexual development in Plasmodium. Parasitology 86:7–28.
    421.
    Sinden R. E.2004. A proteomic analysis of malaria biology: integration of old literature and new technologies. Int. J. Parasitol. 34:1441–1450.
    422.
    Sinden R. E.1983. Sexual development of malarial parasites. Adv. Parasitol. 22:153–216.
    423.
    Sinden R. E., Butcher G. A., Billker O., and Fleck S. L..1996. Regulation of infectivity of Plasmodium to the mosquito vector. Adv. Parasitol. 38:53–117.
    424.
    Sinden R. E. and Gilles H. M..2002. The malaria parasites, p. 8–35. InWarrel D. A. and Gilles H. M. (ed.), Essential malariology, 4th ed. Hodder Arnold, London, United Kingdom.
    425.
    Sinden R. E. and Smalley M. E..1976. Gametocytes of Plasmodium falciparum: phagocytosis by leucocytes in vivo and in vitro. Trans. R. Soc. Trop. Med. Hyg. 70:344–345.
    426.
    Smalley M. E.1977. Plasmodium falciparum gametocytes: the effect of chloroquine on their development. Trans. R. Soc. Trop. Med. Hyg. 71:526–529.
    427.
    Smalley M. E., Abdalla S., and Brown J..1981. The distribution of Plasmodium falciparum in the peripheral blood and bone marrow of Gambian children. Trans. R. Soc. Trop. Med. Hyg. 75:103–105.
    428.
    Smalley M. E. and Brown J..1981. Plasmodium falciparum gametocytogenesis stimulated by lymphocytes and serum from infected Gambian children. Trans. R. Soc. Trop. Med. Hyg. 75:316–317.
    429.
    Smalley M. E. and Sinden R. E..1977. Plasmodium falciparum gametocytes: their longevity and infectivity. Parasitology 74:1–8.
    430.
    Smith D. L. and Hay S. I..2009. Endemicity response timelines for Plasmodium falciparum elimination. Malar. J. 8:87.
    431.
    Smith D. L., McKenzie F. E., Snow R. W., and Hay S. I..2007. Revisiting the basic reproductive number for malaria and its implications for malaria control. PLoS Biol. 5:e42.
    432.
    Smith J. D. et al.1995. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82:101–110.
    433.
    Smith T., Charlwood J. D., Takken W., Tanner M., and Spiegelhalter D. J..1995. Mapping the densities of malaria vectors within a single village. Acta Trop. 59:1–18.
    434.
    Smith T. A., Chitnis N., Briet O. J., and Tanner M.. Uses of mosquito-stage transmission-blocking vaccines against Plasmodium falciparum. Trends Parasitol., in press.
    435.
    Smith T. G., Lourenco P., Carter R., Walliker D., and Ranford-Cartwright L. C..2000. Commitment to sexual differentiation in the human malaria parasite, Plasmodium falciparum. Parasitology 121:127–133.
    436.
    Smith T. G. et al.2003. CD36-mediated nonopsonic phagocytosis of erythrocytes infected with stage I and IIA gametocytes of Plasmodium falciparum. Infect. Immun. 71:393–400.
    437.
    Smithuis F. et al.2006. Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison. Lancet 367:2075–2085.
    438.
    Smithuis F. et al.2010. Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial. Lancet Infect. Dis. 10:673–681.
    439.
    Snounou G. et al.1993. High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Mol. Biochem. Parasitol. 61:315–320.
    440.
    Sokhna C. S., Trape J. F., and Robert V..2001. Gametocytaemia in Senegalese children with uncomplicated falciparum malaria treated with chloroquine, amodiaquine or sulfadoxine + pyrimethamine. Parasite 8:243–250.
    441.
    Song J. et al.2010. Rapid and effective malaria control in Cambodia through mass administration of artemisinin-piperaquine. Malar. J. 9:57.
    442.
    Sowunmi A., Balogun S. T., Gbotosho G. O., and Happi C. T..2008. Plasmodium falciparum gametocyte sex ratios in children with acute, symptomatic, uncomplicated infections treated with amodiaquine. Malar. J. 7:169.
    443.
    Sowunmi A., Balogun S. T., Gbotosho G. O., and Happi C. T..2008. Some features of primary and recrudescent amodiaquine-resistant Plasmodium falciparum infections in Nigerian children. Mem. Inst. Oswaldo Cruz 103:754–759.
    444.
    Sowunmi A. et al.2008. Activities of artemether-lumefantrine and amodiaquine-sulfalene-pyrimethamine against sexual-stage parasites in falciparum malaria in children. Chemotherapy 54:201–208.
    445.
    Sowunmi A. et al.2007. Activities of amodiaquine, artesunate, and artesunate-amodiaquine against asexual- and sexual-stage parasites in falciparum malaria in children. Antimicrob. Agents Chemother. 51:1694–1699.
    446.
    Sowunmi A. and Fateye B. A..2003. Changes in Plasmodium falciparum gametocytaemia in children with chloroquine-sensitive asexual infections. Parasite 10:363–369.
    447.
    Sowunmi A. and Fateye B. A..2003. Gametocyte sex ratios in children with asymptomatic, recrudescent, pyrimethamine-sulfadoxine-resistant, Plasmodium falciparum malaria. Ann. Trop. Med. Parasitol. 97:671–682.
    448.
    Sowunmi A. and Fateye B. A..2003. Plasmodium falciparum gametocytaemia in Nigerian children: before, during and after treatment with antimalarial drugs. Trop. Med. Int. Health 8:783–792.
    449.
    Sowunmi A. et al.2005. Effects of antifolates—co-trimoxazole and pyrimethamine-sulfadoxine—on gametocytes in children with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria. Mem. Inst. Oswaldo Cruz 100:451–455.
    450.
    Sowunmi A., Fateye B. A., Adedeji A. A., Fehintola F. A., and Happi T. C..2004. Risk factors for gametocyte carriage in uncomplicated falciparum malaria in children. Parasitology 129:255–262.
    451.
    Sowunmi A. et al.2009. Therapeutic efficacy and effects of artesunate-mefloquine and mefloquine alone on malaria-associated anemia in children with uncomplicated Plasmodium falciparum malaria in southwest Nigeria. Am. J. Trop. Med. Hyg. 81:979–986.
    452.
    Sowunmi A. et al.2009. Effects of mefloquine and artesunate mefloquine on the emergence, clearance and sex ratio of Plasmodium falciparum gametocytes in malarious children. Malar. J. 8:297.
    453.
    Spielman A. et al.1988. Malaria diagnosis by direct observation of centrifuged samples of blood. Am. J. Trop. Med. Hyg. 39:337–342.
    454.
    Staedke S. G. et al.2004. Combination treatments for uncomplicated falciparum malaria in Kampala, Uganda: randomised clinical trial. Lancet 364:1950–1957.
    455.
    Stepniewska K. et al.2008. Plasmodium falciparum gametocyte dynamics in areas of different malaria endemicity. Malar. J. 7:249.
    456.
    Strickland G. T., Fox E., Sarwar M., Khaliq A. A., and Macdonald M..1986. Effects of chloroquine, amodiaquine and pyrimethamine-sulfadoxine on Plasmodium falciparum gametocytemia. Am. J. Trop. Med. Hyg. 35:259–262.
    457.
    Struik S. S. and Riley E. M..2004. Does malaria suffer from lack of memory? Immunol. Rev. 201:268–290.
    458.
    Sutherland C. J.2001. Stevor transcripts from Plasmodium falciparum gametocytes encode truncated polypeptides. Mol. Biochem. Parasitol. 113:331–335.
    459.
    Sutherland C. J.2009. Surface antigens of Plasmodium falciparum gametocytes—a new class of transmission-blocking vaccine targets? Mol. Biochem. Parasitol. 166:93–98.
    460.
    Sutherland C. J. et al.2002. Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes. Am. J. Trop. Med. Hyg. 67:578–585.
    461.
    Sutherland C. J. et al.2005. Reduction of malaria transmission to Anopheles mosquitoes with a six-dose regimen of co-artemether. PLoS Med. 2:e92.
    462.
    Suwanabun N. et al.2001. Development of a method for the in vitro production of Plasmodium vivax ookinetes. J. Parasitol. 87:928–930.
    463.
    Suwanarusk R. et al.2004. The deformability of red blood cells parasitized by Plasmodium falciparum and P. vivax. J. Infect. Dis. 189:190–194.
    464.
    Talman A. M., Domarle O., McKenzie F. E., Ariey F., and Robert V..2004. Gametocytogenesis: the puberty of Plasmodium falciparum. Malar. J. 3:24.
    465.
    Talman A. M. et al.2004. Influence of chemotherapy on the Plasmodium gametocyte sex ratio of mice and humans. Am. J. Trop. Med. Hyg. 71:739–744.
    466.
    Targett G. et al.2001. Artesunate reduces but does not prevent posttreatment transmission of Plasmodium falciparum to Anopheles gambiae. J. Infect. Dis. 183:1254–1259.
    467.
    Targett G. A.1988. Plasmodium falciparum: natural and experimental transmission-blocking immunity. Immunol. Lett. 19:235–240.
    468.
    Taylor D., Cloonan N., Mann V., Cheng Q., and Saul A..2000. Sequence diversity in rodent malaria of the Pfs28 ookinete surface antigen homologs. Mol. Biochem. Parasitol. 110:429–434.
    469.
    Taylor L. H. and Read A. F..1997. Why so few transmission stages? Reproductive restraint by malaria parasites. Parasitol. Today 13:135–140.
    470.
    Taylor P. J. and Hurd H..2001. The influence of host haematocrit on the blood feeding success of Anopheles stephensi: implications for enhanced malaria transmission. Parasitology 122:491–496.
    471.
    Taylor W. R. and White N. J..2004. Antimalarial drug toxicity: a review. Drug Saf. 27:25–61.
    472.
    Tchuinkam T. et al.1993. Experimental infections of Anopheles gambiae with Plasmodium falciparum of naturally infected gametocyte carriers in Cameroon: factors influencing the infectivity to mosquitoes. Trop. Med. Parasitol. 44:271–276.
    473.
    Templeton T. J. and Kaslow D. C..1999. Identification of additional members define a Plasmodium falciparum gene superfamily which includes Pfs48/45 and Pfs230. Mol. Biochem. Parasitol. 101:223–227.
    474.
    Terlouw D. J. et al.2003. Treatment history and treatment dose are important determinants of sulfadoxine-pyrimethamine efficacy in children with uncomplicated malaria in Western Kenya. J. Infect. Dis. 187:467–476.
    475.
    Thomson J. G. and Robertson A..1935. The structure and development of Plasmodium falciparum gametocytes in the internal organs and peripheral circulation. Trans. R. Soc. Trop. Med. Hyg. 29:31–40.
    476.
    Tjitra E., Suprianto S., and Anstey N. M..2002. Higher gametocyte prevalence following failure of treatment of Plasmodium falciparum malaria with sulfadoxine-pyrimethamine and the combination of chloroquine plus sulfadoxine-pyrimethamine: implications for progression of anti-folate resistance. Trans. R. Soc. Trop. Med. Hyg. 96:434–437.
    477.
    Tomas A. M. et al.2001. P25 and P28 proteins of the malaria ookinete surface have multiple and partially redundant functions. EMBO J. 20:3975–3983.
    478.
    Toure Y. T. et al.1998. Gametocyte infectivity by direct mosquito feeds in an area of seasonal malaria transmission: implications for Bancoumana, Mali as a transmission-blocking vaccine site. Am. J. Trop. Med. Hyg. 59:481–486.
    479.
    Trager W.2005. What triggers the gametocyte pathway in Plasmodium falciparum? Trends Parasitol. 21:262–264.
    480.
    Trager W. and Gill G. S..1992. Enhanced gametocyte formation in young erythrocytes by Plasmodium falciparum in vitro. J. Protozool. 39:429–432.
    481.
    Trager W. and Gill G. S..1989. Plasmodium falciparum gametocyte formation in vitro: its stimulation by phorbol diesters and by 8-bromo cyclic adenosine monophosphate. J. Protozool. 36:451–454.
    482.
    Trager W., Gill G. S., Lawrence C., and Nagel R. L..1999. Plasmodium falciparum: enhanced gametocyte formation in vitro in reticulocyte-rich blood. Exp. Parasitol. 91:115–118.
    483.
    Trubowitz S. and Masek B..1968. Plasmodium falciparum: phagocytosis by polymorphonuclear leukocytes. Science 162:273–274.
    484.
    Tsuboi T. et al.1998. Sequence polymorphism in two novel Plasmodium vivax ookinete surface proteins, Pvs25 and Pvs28, that are malaria transmission-blocking vaccine candidates. Mol. Med. 4:772–782.
    485.
    Tsuboi T., Tachibana M., Kaneko O., and Torii M..2003. Transmission-blocking vaccine of vivax malaria. Parasitol. Int. 52:1–11.
    486.
    Udomsangpetch R., Kaneko O., Chotivanich K., and Sattabongkot J..2008. Cultivation of Plasmodium vivax. Trends Parasitol. 24:85–88.
    487.
    Vale N., Moreira R., and Gomes P..2009. Primaquine revisited six decades after its discovery. Eur. J. Med. Chem. 44:937–953.
    488.
    van den Berghe L., Chardome M., and Peel E..1952. Supériorité des préparations de scarification du derme sur les préparations de sang périphérique pour le diagnostic de malaria. An. Inst. Med. Trop. 9:553–562.
    489.
    van den Broek I. V. et al.2005. Efficacy of chloroquine + sulfadoxine-pyrimethamine, mefloquine + artesunate and artemether + lumefantrine combination therapies to treat Plasmodium falciparum malaria in the Chittagong Hill Tracts, Bangladesh. Trans. R. Soc. Trop. Med. Hyg. 99:727–735.
    490.
    van der Kolk M. et al.2004. Evaluation of the standard membrane feeding assay (SMFA) for the determination of malaria transmission reducing activity using empirical data. Parasitology 130:13–22.
    491.
    van der Kolk M., de Vlas S. J., and Sauerwein R. W..2006. Reduction and enhancement of Plasmodium falciparum transmission by endemic human sera. Int. J. Parasitol. 36:1091–1095.
    492.
    van der Kolk M. et al.2003. Transmission of Plasmodium falciparum in urban Yaoundé, Cameroon, is seasonal and age-dependent. Trans. R. Soc. Trop. Med. Hyg. 97:375–379.
    493.
    van Dijk M. R. et al.2001. A central role for P48/45 in malaria parasite male gamete fertility. Cell 104:153–164.
    494.
    van Dijk M. R. et al.2010. Three members of the 6-cys protein family of Plasmodium play a role in gamete fertility. PLoS Pathog. 6:e1000853.
    495.
    Van Geertruyden J. P. and D'Alessandro U..2007. Malaria and HIV: a silent alliance. Trends Parasitol. 23:465–467.
    496.
    Van Geertruyden J. P., Menten J., Colebunders R., Korenromp E., and D'Alessandro U..2008. The impact of HIV-1 on the malaria parasite biomass in adults in sub-Saharan Africa contributes to the emergence of antimalarial drug resistance. Malar. J. 7:134.
    497.
    Van Geertruyden J. P. et al.2006. HIV-1 immune suppression and antimalarial treatment outcome in Zambian adults with uncomplicated malaria. J. Infect. Dis. 194:917–925.
    498.
    van Schaijk B. C. et al.2006. Pfs47, paralog of the male fertility factor Pfs48/45, is a female specific surface protein in Plasmodium falciparum. Mol. Biochem. Parasitol. 149:216–222.
    499.
    Vermeulen A. N. et al.1985. Sequential expression of antigens on sexual stages of Plasmodium falciparum accessible to transmission-blocking antibodies in the mosquito. J. Exp. Med. 162:1460–1476.
    500.
    Vermeulen A. N. et al.1986. Characterization of Plasmodium falciparum sexual stage antigens and their biosynthesis in synchronised gametocyte cultures. Mol. Biochem. Parasitol. 20:155–163.
    501.
    Vogel G.2010. The ‘do unto others’ malaria vaccine. Nature 238:847–848.
    502.
    von Seidlein L., Drakeley C., Greenwood B., Walraven G., and Targett G..2001. Risk factors for gametocyte carriage in Gambian children. Am. J. Trop. Med. Hyg. 65:523–527.
    503.
    von Seidlein L. and Greenwood B. M..2003. Mass administrations of antimalarial drugs. Trends Parasitol. 19:452–460.
    504.
    von Seidlein L. et al.2000. Efficacy of artesunate plus pyrimethamine-sulphadoxine for uncomplicated malaria in Gambian children: a double-blind, randomised, controlled trial. Lancet 355:352–357.
    505.
    Wang C. W. et al.2010. Identification of a major rif transcript common to gametocytes and sporozoites of Plasmodium falciparum. Malar. J. 9:147.
    506.
    Weerasinghe K. L. et al.2002. A safety and efficacy trial of artesunate, sulphadoxine-pyrimethamine and primaquine in P falciparum malaria. Ceylon Med. J. 47:83–85.
    507.
    Westenberger S. J. et al.2010. A systems-based analysis of Plasmodium vivax lifecycle transcription from human to mosquito. PLoS Negl. Trop. Dis. 4:e653.
    508.
    White L. J. et al.2009. The role of simple mathematical models in malaria elimination strategy design. Malar. J. 8:212.
    509.
    White N. J.2008. Qinghaosu (artemisinin): the price of success. Science 320:330–334.
    510.
    White N. J.2008. The role of anti-malarial drugs in eliminating malaria. Malar. J. 7(Suppl. 1):S8.
    511.
    Whitten M. M., Shiao S. H., and Levashina E. A..2006. Mosquito midguts and malaria: cell biology, compartmentalization and immunology. Parasite Immunol. 28:121–130.
    512.
    Whitworth J. et al.2000. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet 356:1051–1056.
    513.
    Williams J. L.1999. Stimulation of Plasmodium falciparum gametocytogenesis by conditioned medium from parasite cultures. Am. J. Trop. Med. Hyg. 60:7–13.
    514.
    Williamson K. C.2003. Pfs230: from malaria transmission-blocking vaccine candidate toward function. Parasite Immunol. 25:351–359.
    515.
    Williamson K. C., Criscio M. D., and Kaslow D. C..1993. Cloning and expression of the gene for Plasmodium falciparum transmission-blocking target antigen, Pfs230. Mol. Biochem. Parasitol. 58:355–358.
    516.
    Williamson K. C., Fujioka H., Aikawa M., and Kaslow D. C..1996. Stage-specific processing of Pfs230, a Plasmodium falciparum transmission-blocking vaccine candidate. Mol. Biochem. Parasitol. 78:161–169.
    517.
    Williamson K. C., Keister D. B., Muratova O., and Kaslow D. C..1995. Recombinant Pfs230, a Plasmodium falciparum gametocyte protein, induces antisera that reduce the infectivity of Plasmodium falciparum to mosquitoes. Mol. Biochem. Parasitol. 75:33–42.
    518.
    Wong J. L., Leydon A. R., and Johnson M. A..2010. HAP2(GCS1)-dependent gamete fusion requires a positively charged carboxy-terminal domain. PLoS Genet. 6:e1000882.
    519.
    Woolhouse M. E. et al.1997. Heterogeneities in the transmission of infectious agents: implications for the design of control programs. Proc. Natl. Acad. Sci. U. S. A. 94:338–342.
    520.
    World Health Organization.2008. Global malaria control and elimination: report of a technical review. WHO, Geneva, Switzerland. http://www.who.int/malaria/publications/atoz/9789241596756.
    521.
    World Health Organization.2006. Guidelines for the treatment of malaria. WHO/HTM/MAL/2006.1108. WHO, Geneva, Switzerland.
    522.
    World Health Organization.2000. Malaria transmission blocking vaccines: an ideal public good. WHO document number TDR/RBM/MAL/VAC/2000.1. WHO, Geneva, Switzerland.
    523.
    Wozencraft A. O., Dockrell H. M., Taverne J., Targett G. A., and Playfair J. H..1984. Killing of human malaria parasites by macrophage secretory products. Infect. Immun. 43:664–669.
    524.
    Wu Y. et al.2008. Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51. PLoS One 3:e2636.
    525.
    Wu Y. et al.2006. Sustained high-titer antibody responses induced by conjugating a malarial vaccine candidate to outer-membrane protein complex. Proc. Natl. Acad. Sci. U. S. A. 103:18243–18248.
    526.
    Yeka A. et al.2005. Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in Uganda. PLoS Med. 2:e190.
    527.
    Yeka A. et al.2008. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS One 3:e2390.
    528.
    Young J. A. et al.2005. The Plasmodium falciparum sexual development transcriptome: a microarray analysis using ontology-based pattern identification. Mol. Biochem. Parasitol. 143:67–79.
    529.
    Zimmerman P. A., Thomson J. M., Fujioka H., Collins W. E., and Zborowski M..2006. Diagnosis of malaria by magnetic deposition microscopy. Am. J. Trop. Med. Hyg. 74:568–572.
    530.
    Zongo I. et al.2007. Randomized comparison of amodiaquine plus sulfadoxine-pyrimethamine, artemether-lumefantrine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso. Clin. Infect. Dis. 45:1453–1461.
    531.
    Zoungrana A. et al.2008. Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso. PLoS One 3:e1630.
    532.
    Zwang J. et al.2009. Safety and efficacy of dihydroartemisinin-piperaquine in falciparum malaria: a prospective multi-centre individual patient data analysis. PLoS One 4:e6358.

    Author Bios

    Teun Bousema
    Department of Immunology & Infection, London School of Hygiene and Tropical Medicine, London W1CE 7HT, United Kingdom
    Teun Bousema is an epidemiologist at the London School of Hygiene & Tropical Medicine, London, United Kingdom. He attended the Radboud University Nijmegen, Nijmegen, Netherlands (M.Sc. and Ph.D.), and subsequently worked in Kenya, Tanzania, Uganda, and Mali on clinical and epidemiological projects focusing on malaria transmission-reducing interventions.
    Chris Drakeley [email protected]
    Department of Immunology & Infection, London School of Hygiene and Tropical Medicine, London W1CE 7HT, United Kingdom
    Chris Drakeley is an immunologist based at the London School of Hygiene & Tropical Medicine, London, United Kingdom. He did his Ph.D. studies in the Gambia, examining malaria infectivity. He subsequently worked in Tanzania for 10 years, at Ifakara Health Institute and the Joint Malaria Programme, Moshi, focusing on defining malaria transmission dynamics. Now based in the United Kingdom, he is involved in monitoring and evaluation of malaria control projects in a number of countries in Africa and Southeast Asia.

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    Clinical Microbiology Reviews
    Volume 24Number 2April 2011
    Pages: 377 - 410

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    Teun Bousema
    Department of Immunology & Infection, London School of Hygiene and Tropical Medicine, London W1CE 7HT, United Kingdom
    Chris Drakeley [email protected]
    Department of Immunology & Infection, London School of Hygiene and Tropical Medicine, London W1CE 7HT, United Kingdom

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  • Clinical Microbiology ReviewsArticle
    Early Events in Coccidioidomycosis

    SUMMARY

    Since its description nearly 130 years ago, hundreds of studies have deepened our understanding of coccidioidomycosis, also known as valley fever (VF), and provided useful diagnostic tests and treatments for the disease caused by the dimorphic fungi Coccidioides spp. In general, most of the literature has addressed well-established infections and has described patients who have experienced major complications. In contrast, little attention has been given to the earliest consequences of the pathogen-host interaction and its implications for disease manifestation, progression, and resolution. The purpose of this review is to highlight published studies on early coccidioidomycosis, identify gaps in our knowledge, and suggest new or former research areas that might be or remain fertile ground for insight into the early stages of this invasive fungal disease.

    REFERENCES

    1.
    Posadas A. 1892. Un nuevo caso de micosis fungoidea con psorospermias. An Circ Med Argent 15:585–597.
    2.
    Ophuls W, Moffitt HC. 1900. A new pathogenic mould. (Formerly described as a protozoon: Coccidioides immitis pyogenes.) Preliminary report. Philadelphia Med J 5:1471–1472.
    3.
    Ophuls W. 1905. Further observations on a pathogenic mold formerly described as a protozoan (Coccidioides immitis, Coccidioides pyogenes). J Exp Med 6:443–486.
    4.
    Teixeira MM, Barker BM. 2016. Use of population genetics to assess the ecology, evolution, and population structure of Coccidioides. Emerg Infect Dis 22:1022–1030.
    5.
    Teixeria MM, Barker B. 2017. Coccidioides and coccidioidomycosis, p 255–280. In Mora-Montes H, Lopes-Bezerra L (ed), Current progress in medical mycology. Springer, Cham, Switzerland.
    6.
    Dickson EC, Gifford MA. 1938. Coccidioides infection (coccidioidomycosis). II. The primary type of infection. Arch Intern Med 62:853–871.
    7.
    Smith CE, Beard RR. 1946. Effect of season and dust control on coccidioidomycosis. JAMA 132:833–838.
    8.
    Baker O, Braude AI. 1956. A study of stimuli leading to the prodution of spherules in coccidioidomycosis. J Lab Clin Med 47:169–181.
    9.
    Beaman L, Holmberg CA. 1980. In vitro response of alveolar macrophages to infection with Coccidioides immitis. Infect Immun 28:594–600.
    10.
    Cole GT, Sun SH. 1985. Arthroconidium-spherule-endospore transformation in Coccidioides immitis, p 281–333. In Szaniszlo PJ (ed), Fungal dimorphism. Plenum Publishing Corp., New York, NY.
    11.
    Lewis ER, Bowers JR, Barker BM. 2015. Dust devil: the life and times of the fungus that causes valley fever. PLoS Pathog 11:e1004762.
    12.
    Cole GT, Hung CY. 2001. The parasitic cell wall of Coccidioides immitis. Med Mycol 39:31–40.
    13.
    Ganesan S, Comstock AT, Sajjan US. 2013. Barrier function of airway tract epithelium. Tissue Barriers 1:e24997.
    14.
    Ampel NM, Hoover SE. 2015. Pathogenesis of coccidioidomycosis. Curr Fungal Infect Rep 9:253–258.
    15.
    Drutz DJ, Huppert M. 1983. Coccidioidomycosis: factors affecting the host-parasite interaction. J Infect Dis 147:372–390.
    16.
    Werner JL, Steele C. 2014. Innate receptors and cellular defense against pulmonary infections. J Immunol 193:3842–3850.
    17.
    Chen K, Kolls JK. 2013. T cell-mediated host immune defenses in the lung. Annu Rev Immunol 31:605–633.
    18.
    Smith CE, Beard RR, Whiting EG, Rosenberger HG. 1946. Varieties of coccidioidal infection in relation to the epidemiology and control of the disease. Am J Public Health Nations Health 36:1394–1402.
    19.
    Valdivia L, Nix D, Wright M, Lindberg E, Fagan T, Lieberman D, Stoffer T, Ampel NM, Galgiani JN. 2006. Coccidioidomycosis as a common cause of community-acquired pneumonia. Emerg Infect Dis 12:958–962.
    20.
    Ampel NM. 2015. The treatment of coccidioidomycosis. Rev Inst Med Trop Sao Paulo 57(Suppl 19):51–56.
    21.
    Galgiani JN, Thompson GR, III, Board of Valley Fever Alliance of Arizona Clinicians. 2016. Valley Fever (coccidioidomycosis) tutorial for primary care professionals. Valley Fever Center for Excellence, The University of Arizona, Tucson, AZ. http://www.vfce.arizona.edu/sites/vfce/files/tutorial_for_primary_care_professionals.pdf.
    22.
    Smith CE. 1940. Epidemiology of acute coccidioidomycosis with erythema nodosum. Am J Public Health Nations Health 30:600–611.
    23.
    Fiese MJ, Cheu S, Sorensen RH. 1955. Mycelial forms of Coccidioides immitis in sputum and tissues of the human host. Ann Intern Med 43:255–270.
    24.
    Drutz DJ, Catanzaro A. 1978. Coccidioidomycosis. Part II. Am Rev Respir Dis 117:727–771.
    25.
    Thompson GR, III, Bays D, Taylor SL, Cohen SH, Pappagianis D. 2013. Association between serum 25-hydroxyvitamin D level and type of coccidioidal infection. Med Mycol 51:319–323.
    26.
    Vinh DC, Masannat F, Dzioba RB, Galgiani JN, Holland SM. 2009. Refractory disseminated coccidioidomycosis and mycobacteriosis in interferon-gamma receptor 1 deficiency. Clin Infect Dis 49:e62–e65.
    27.
    Odio CD, Marciano BE, Galgiani JN, Holland SM. 2017. Risk factors for disseminated coccidioidomycosis, United States. Emerg Infect Dis 23:4.
    28.
    Huppert M, Sun SH, Harrison JL. 1982. Morphogenesis throughout saprobic and parasitic cycles of Coccidioides immitis. Mycopathologia 78:107–122.
    29.
    Mead HL, Teixeira MM, Galgiani JN, Barker BM. 2018. Characterizing in vitro spherule morphogenesis of multiple strains of both species of Coccidioides. Med Mycol 57:478–488.
    30.
    Hussell T, Bell TJ. 2014. Alveolar macrophages: plasticity in a tissue-specific context. Nat Rev Immunol 14:81–93.
    31.
    Converse JL. 1955. Growth of spherules of Coccidioides immitis in a chemically defined liquid medium (22144). Proc Soc Exp Biol Med 90:709–711.
    32.
    Converse JL. 1957. Effect of surface active agents on endosporulation of Coccidioides immitis in a chemically defined medium. J Bacteriol 74:106–107.
    33.
    Lones GW, Peacock CL. 1960. Studies of the growth and metabolism of Coccidioides immitis. Ann N Y Acad Sci 89:102–108.
    34.
    Lones GW, Peacock CL. 1960. Role of carbon dioxide in the dimorphism of Coccidioides immitis. J Bacteriol 79:308–309.
    35.
    Breslau AM, Kubota MY. 1964. Continuous in vitro cultivation of spherules of Coccidioides immitis. J Bacteriol 87:468–472.
    36.
    Wheat RW, Tritschler C, Conant NF, Lowe EP. 1977. Comparison of Coccidioides immitis arthrospore, mycelium, and spherule cell walls, and influence of growth medium on mycelial cell wall composition. Infect Immun 17:91–97.
    37.
    Cole GT, Kirkland TN, Sun SH. 1987. An immunoreactive, water-soluble conidial wall fraction of Coccidioides immitis. Infect Immun 55:657–667.
    38.
    Bayry J, Aimanianda V, Guijarro JI, Sunde M, Latge JP. 2012. Hydrophobins—unique fungal proteins. PLoS Pathog 8:e1002700.
    39.
    Ward ER, Jr, Cox RA, Schmitt JA, Jr, Huppert M, Sun SH. 1975. Delayed-type hypersensitivity responses to a cell wall fraction of the mycelial phase of Coccidioides immitis. Infect Immun 12:1093–1097.
    40.
    Cox RA, Huppert M, Starr P, Britt LA. 1984. Reactivity of alkali-soluble, water-soluble cell wall antigen of Coccidioides immitis with anti-Coccidioides immunoglobulin M precipitin antibody. Infect Immun 43:502–507.
    41.
    Kirkland TN, Zhu S, Kruse D, Hsu L, Seshan KR, Cole GT. 1991. Coccidioides immitis fractions which are antigenic for immune T lymphocytes. Infect Immun 59:3952–3961.
    42.
    Cox RA, Magee DM. 2004. Coccidioidomycosis: host response and vaccine development. Clin Microbiol Rev 17:804–839.
    43.
    Awasthi S, Vilekar P, Conkleton A, Rahman N. 2019. Dendritic cell-based immunization induces Coccidioides Ag2/PRA-specific immune response. Vaccine 37:1685–1691.
    44.
    Cole GT, Pshko EJ, Seshan KR. 1995. Possible roles of wall hydrolases in the morphogenesis of Coccidioides immitis. Can J Bot 73:132–S1141.
    45.
    Breslau AM, Hensley TJ, Erickson JO. 1961. Electron microscopy of cultured spherules of Coccidioides immitis. J Biophys Biochem Cytol 9:627–637.
    46.
    Li L, Schmelz M, Kellner EM, Galgiani JN, Orbach MJ. 2007. Nuclear labeling of Coccidioides posadasii with green fluorescent protein. Ann N Y Acad Sci 1111:198–207.
    47.
    Hector RF, Pappagianis D. 1982. Enzymatic degradation of the walls of spherules of Coccidioides immitis. Exp Mycol 6:136–152.
    48.
    Frey CL, Drutz DJ. 1986. Influence of fungal surface components on the interaction of Coccidioides immitis with polymorphonuclear neutrophils. J Infect Dis 153:933–943.
    49.
    Lee CY, Thompson GR, Hastey CJ, Hodge GC, Lunetta JM, Pappagianis D, Heinrich V. 2015. Coccidioides endospores and spherules draw strong chemotactic, adhesive, and phagocytic responses by individual human neutrophils. PLoS One 10:e0129522.
    50.
    Hung CY, Yu JJ, Seshan KR, Reichard U, Cole GT. 2002. A parasitic phase-specific adhesin of Coccidioides immitis contributes to the virulence of this respiratory fungal pathogen. Infect Immun 70:3443–3456.
    51.
    Hung CY, Seshan KR, Yu JJ, Schaller R, Xue J, Basrur V, Gardner MJ, Cole GT. 2005. A metalloproteinase of Coccidioides posadasii contributes to evasion of host detection. Infect Immun 73:6689–6703.
    52.
    Viriyakosol S, Fierer J, Brown GD, Kirkland TN. 2005. Innate immunity to the pathogenic fungus Coccidioides posadasii is dependent on Toll-like receptor 2 and Dectin-1. Infect Immun 73:1553–1560.
    53.
    Beaman L, Benjamini E, Pappagianis D. 1983. Activation of macrophages by lymphokines: enhancement of phagosome-lysosome fusion and killing of Coccidioides immitis. Infect Immun 39:1201–1207.
    54.
    Viriyakosol S, Jimenez MDP, Saijo S, Fierer J. 2014. Neither dectin-2 nor the mannose receptor is required for resistance to Coccidioides immitis in mice. Infect Immun 82:1147–1156.
    55.
    Garcia-Sherman MC, Lundberg T, Sobonya RE, Lipke PN, Klotz SA. 2015. A unique biofilm in human deep mycoses: fungal amyloid is bound by host serum amyloid P component. NPJ Biofilms Microbiomes 1:15009.
    56.
    Wiesner DL, Klein BS. 2017. Lung epithelium: barrier immunity to inhaled fungi and driver of fungal-associated allergic asthma. Curr Opin Microbiol 40:8–13.
    57.
    Whitsett JA, Alenghat T. 2015. Respiratory epithelial cells orchestrate pulmonary innate immunity. Nat Immunol 16:27–35.
    58.
    Awasthi S, Magee DM, Coalson JJ. 2004. Coccidioides posadasii infection alters the expression of pulmonary surfactant proteins (SP)-A and SP-D. Respir Res 5:28.
    59.
    Leiva-Juarez MM, Kolls JK, Evans SE. 2018. Lung epithelial cells: therapeutically inducible effectors of antimicrobial defense. Mucosal Immunol 11:21–34.
    60.
    Austwick PKC. 1980. The pathogenic aspects of the use of fungi: the need for risk analysis and registration of fungi. Ecol Bull 31:91–102.
    61.
    Deresinski SC, Levine HB, Stevens DA. 1978. Coccidioides immitis endospores: phagocytosis by human cells. Mycopathologia 64:179–181.
    62.
    Nesbit LA, Knox KS, Nguyen CT, Roesch J, Wheat LJ, Johnson SM, Pappagianis D, Chavez S, Ampel NM. 2013. Immunological characterization of bronchoalveolar lavage fluid in patients with acute pulmonary coccidioidomycosis. J Infect Dis 208:857–863.
    63.
    Levine HB, Miller RL, Smith CE. 1962. Influence of vaccination on respiratory coccidioidal disease in cynomolgus monkeys. J Immunol 89:242–251.
    64.
    Williams PL, Sobel RA, Sorensen KN, Clemons KV, Shuer LM, Royaltey SS, Yao Y, Pappagianis D, Lutz JE, Reed C, River ME, Lee BC, Bhatti SU, Stevens DA. 1998. A model of coccidioidal meningoencephalitis and cerebrospinal vasculitis in the rabbit. J Infect Dis 178:1217–1221.
    65.
    Clemons KV, Capilla J, Stevens DA. 2007. Experimental animal models of coccidioidomycosis. Ann N Y Acad Sci 1111:208–224.
    66.
    Werner SB, Pappagianis D, Heindl I, Mickel A. 1972. An epidemic of coccidioidomycosis among archeology students in northern California. N Engl J Med 286:507–512.
    67.
    Jamison HW, Carter RA. 1947. The roentgen findings in early coccidioidomycosis. Radiology 48:323–332.
    68.
    Jude CM, Nayak NB, Patel MK, Deshmukh M, Batra P. 2014. Pulmonary coccidioidomycosis: pictorial review of chest radiographic and CT findings. Radiographics 34:912–925.
    69.
    Crum NF, Lederman ER, Stafford CM, Parrish JS, Wallace MR. 2004. Coccidioidomycosis: a descriptive survey of a reemerging disease. Clinical characteristics and current controversies. Medicine 83:149–175.
    70.
    Shubitz LF, Dial SM, Perrill R, Casement R, Galgiani JN. 2008. Vaccine-induced cellular immune responses differ from innate responses in susceptible and resistant strains of mice infected with Coccidioides posadasii. Infect Immun 76:5553–5564.
    71.
    Shubitz LP, Lewis ML, Dial SM, Galgiani J. 2011. Early post-infection detection of Coccidioides in intranasally infected mice, p 40. In Proceedings of the 55th Annual Coccidioidomycosis Study Group Meeting.
    72.
    Sun SH, Cole GT, Drutz DJ, Harrison JL. 1986. Electron-microscopic observations of the Coccidioides immitis parasitic cycle in vivo. J Med Vet Mycol 24:183–192.
    73.
    Shubitz LF, Powell DA, Trinh HT, Lewis ML, Orbach MJ, Frelinger JA, Galgiani JN. 2018. Viable spores of Coccidioides posadasii Deltacps1 are required for vaccination and provide long lasting immunity. Vaccine 36:3375–3380.
    74.
    Gonzalez A. 2013. Innate immune response to the dimorphic fungal pathogen Coccidioides: molecular and cellular mechanisms. J Clin Cell Immunol S13:1–6.
    75.
    Erwig LP, Gow NA. 2016. Interactions of fungal pathogens with phagocytes. Nat Rev Microbiol 14:163–176.
    76.
    Lengeler KB, Davidson RC, D'Souza C, Harashima T, Shen W-C, Wang P, Pan X, Waugh M, Heitman J. 2000. Signal transduction cascades regulating fungal development and virulence. Microbiol Mol Biol Rev 64:746–785.
    77.
    Runyanga TJ, Chen Y, Sun F. 2017. Cell communication and fungal virulence: a review. Res Rev Res J Biol 5:8–16.
    78.
    Gauthier G, Klein BS. 2008. Insights into fungal morphogenesis and immune evasion: fungal conidia, when situated in mammalian lungs, may switch from mold to pathogenic yeasts or spore-forming spherules. Microbe Wash DC 3:416–423.
    79.
    Pishko EJ, Kirkland TN, Cole GT. 1995. Isolation and characterization of two chitinase-encoding genes (cts1, cts2) from the fungus Coccidioides immitis. Gene 167:173–177.
    80.
    Abuodeh RO, Orbach MJ, Mandel MA, Das A, Galgiani JN. 2000. Genetic transformation of Coccidioides immitis facilitated by Agrobacterium tumefaciens. J Infect Dis 181:2106–2110.
    81.
    Mandel MA, Galgiani JN, Kroken S, Orbach MJ. 2006. Coccidioides posadasii contains single chitin synthase genes corresponding to classes I to VII. Fungal Genet Biol 43:775–788.
    82.
    Kellner EM, Orsborn KI, Siegel EM, Mandel MA, Orbach MJ, Galgiani JN. 2005. Coccidioides posadasii contains a single 1,3-{beta}-glucan synthase gene that appears to be essential for growth. Eukaryot Cell 4:111–120.
    83.
    Johannesson H, Kasuga T, Schaller RA, Good B, Gardner MJ, Townsend JP, Cole GT, Taylor JW. 2006. Phase-specific gene expression underlying morphological adaptations of the dimorphic human pathogenic fungus, Coccidioides posadasii. Fungal Genet Biol 43:545–559.
    84.
    Delgado N, Hung CY, Tarcha E, Gardner MJ, Cole GT. 2004. Profiling gene expression in Coccidioides posadasii. Med Mycol 42:59–71.
    85.
    Rappleye CA, Goldman WE. 2006. Defining virulence genes in the dimorphic fungi. Annu Rev Microbiol 60:281–303.
    86.
    Whiston E, Zhang Wise H, Sharpton TJ, Jui G, Cole GT, Taylor JW. 2012. Comparative transcriptomics of the saprobic and parasitic growth phases in Coccidioides spp. PLoS One 7:e41034.
    87.
    Viriyakosol S, Singhania A, Fierer J, Goldberg J, Kirkland TN, Woelk CH. 2013. Gene expression in human fungal pathogen Coccidioides immitis changes as arthroconidia differentiate into spherules and mature. BMC Microbiol 13:121.
    88.
    Narra HP, Shubitz LF, Mandel MA, Trinh HT, Griffin K, Buntzman AS, Frelinger JA, Galgiani JN, Orbach MJ. 2016. A Coccidioides posadasii CPS1 deletion mutant is avirulent and protects mice from lethal infection. Infect Immun 84:3007–3016.
    89.
    Grys TE, Kaushal S, Chowdhury Y, Dasari S, Mitchell NM, Magee DM, Blair JE, Colby TV, Lake DF. 2016. Total and lectin-binding proteome of spherulin from Coccidioides posadasii. J Proteome Res 15:3463–3472.
    90.
    Galgiani JN, Payne CM, Jones JF. 1984. Human polymorphonuclear-leukocyte inhibition of incorporation of chitin precursors into mycelia of Coccidioides immitis. J Infect Dis 149:404–412.
    91.
    Galgiani JN. 1986. Inhibition of different phases of Coccidioides immitis by human neutrophils or hydrogen peroxide. J Infect Dis 153:217–222.
    92.
    Ampel NM, Galgiani JN. 1991. Interaction of human peripheral blood mononuclear cells with Coccidioides immitis arthroconidia. Cell Immunol 133:253–262.
    93.
    Rutherford JC. 2014. The emerging role of urease as a general microbial virulence factor. PLoS Pathog 10:e1004062.
    94.
    Li K, Yu JJ, Hung CY, Lehmann PF, Cole GT. 2001. Recombinant urease and urease DNA of Coccidioides immitis elicit an immunoprotective response against coccidioidomycosis in mice. Infect Immun 69:2878–2887.
    95.
    Mirbod-Donovan F, Schaller R, Hung CY, Xue J, Reichard U, Cole GT. 2006. Urease produced by Coccidioides posadasii contributes to the virulence of this respiratory pathogen. Infect Immun 74:504–515.
    96.
    Wise HZ, Hung CY, Whiston E, Taylor JW, Cole GT. 2013. Extracellular ammonia at sites of pulmonary infection with Coccidioides posadasii contributes to severity of the respiratory disease. Microb Pathog 59-60:19–28.
    97.
    Schenten D, Medzhitov R. 2011. The control of adaptive immune responses by the innate immune system. Adv Immunol 109:87–124.
    98.
    Plato A, Hardison SE, Brown GD. 2015. Pattern recognition receptors in antifungal immunity. Semin Immunopathol 37:97–106.
    99.
    Hung C-Y, Jiménez-Alzate MDP, Gonzalez A, Wüthrich M, Klein BS, Cole GT. 2014. Interleukin-1 receptor but not Toll-like receptor 2 is essential for MyD88-dependent Th17 immunity to Coccidioides infection. Infect Immun 82:2106–2114.
    100.
    Wang H, LeBert V, Hung CY, Galles K, Saijo S, Lin X, Cole GT, Klein BS, Wuthrich M. 2014. C-type lectin receptors differentially induce th17 cells and vaccine immunity to the endemic mycosis of North America. J Immunol 192:1107–1119.
    101.
    del Pilar Jimenez AM, Viriyakosol S, Walls L, Datta SK, Kirkland T, Heinsbroek SE, Brown G, Fierer J. 2008. Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a). Genes Immun 9:338–348.
    102.
    Awasthi S, Magee DM. 2004. Differences in expression of cell surface co-stimulatory molecules, Toll-like receptor genes and secretion of IL-12 by bone marrow-derived dendritic cells from susceptible and resistant mouse strains in response to Coccidioides posadasii. Cell Immunol 231:49–55.
    103.
    Awasthi S. 2010. Susceptibility of TLR4-defective C3H/HeJ mice to Coccidioides posadasii infection. Med Mycol 48:470–475.
    104.
    Viriyakosol S, Jimenez MDP, Gurney MA, Ashbaugh ME, Fierer J. 2013. Dectin-1 is required for resistance to coccidioidomycosis in mice. mBio 4:e00597.
    105.
    Kerscher B, Willment JA, Brown GD. 2013. The Dectin-2 family of C-type lectin-like receptors: an update. Int Immunol 25:271–277.
    106.
    Murdock BJ, Falkowski NR, Shreiner AB, Sadighi Akha AA, McDonald RA, White ES, Toews GB, Huffnagle GB. 2012. Interleukin-17 drives pulmonary eosinophilia following repeated exposure to Aspergillus fumigatus conidia. Infect Immun 80:1424–1436.
    107.
    Malacco N, Rachid MA, Gurgel I, Moura TR, Sucupira PHF, de Sousa LP, de Souza DDG, Russo RC, Teixeira MM, Soriani FM. 2018. Eosinophil-associated innate IL-17 response promotes Aspergillus fumigatus lung pathology. Front Cell Infect Microbiol 8:453.
    108.
    Castro-Lopez N, Hung CY. 2017. Immune response to coccidioidomycosis and the development of a vaccine. Microorganisms 5:13.
    109.
    Geijtenbeek TB, Gringhuis SI. 2009. Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol 9:465–479.
    110.
    Hung CY, Castro-Lopez N, Cole GT. 2016. Card9- and MyD88-mediated gamma interferon and nitric oxide production is essential for resistance to subcutaneous Coccidioides posadasii infection. Infect Immun 84:1166–1175.
    111.
    Sampaio EP, Hsu AP, Pechacek J, Bax HI, Dias DL, Paulson ML, Chandrasekaran P, Rosen LB, Carvalho DS, Ding L, Vinh DC, Browne SK, Datta S, Milner JD, Kuhns DB, Long Priel DA, Sadat MA, Shiloh M, De Marco B, Alvares M, Gillman JW, Ramarathnam V, de la Morena M, Bezrodnik L, Moreira I, Uzel G, Johnson D, Spalding C, Zerbe CS, Wiley H, Greenberg DE, Hoover SE, Rosenzweig SD, Galgiani JN, Holland SM. 2013. Signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations and disseminated coccidioidomycosis and histoplasmosis. J Allergy Clin Immunol 131:1624–1634.
    112.
    Fierer J, Walls L, Wright F, Kirkland TN. 1999. Genes influencing resistance to Coccidioides immitis and the interleukin-10 response map to chromosomes 4 and 6 in mice. Infect Immun 67:2916–2919.
    113.
    Nathan C, Shiloh MU. 2000. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc Natl Acad Sci U S A 97:8841–8848.
    114.
    Bogdan C. 2001. Nitric oxide and the immune response. Nat Immunol 2:907–916.
    115.
    Margolis DA, Viriyakosol S, Fierer J, Kirkland TN. 2011. The role of reactive oxygen intermediates in experimental coccidioidomycois in mice. BMC Microbiol 11:71.
    116.
    Gonzalez A, Hung CY, Cole GT. 2011. Coccidioides releases a soluble factor that suppresses nitric oxide production by murine primary macrophages. Microb Pathog 50:100–108.
    117.
    Gonzalez A, Hung CY, Cole GT. 2011. Nitric oxide synthase activity has limited influence on the control of Coccidioides infection in mice. Microb Pathog 51:161–168.
    118.
    Lewis ER, David VR, Doyle AL, Rajabi K, Kiefer JA, Pirrotte P, Barker BM. 2015. Differences in host innate responses among Coccidioides isolates in a murine model of pulmonary coccidioidomycosis. Eukaryot Cell 14:1043–1053.
    119.
    Van Dyken SJ, Liang HE, Naikawadi RP, Woodruff PG, Wolters PJ, Erle DJ, Locksley RM. 2017. Spontaneous chitin accumulation in airways and age-related fibrotic lung disease. Cell 169:497–509.e13.
    120.
    Slagle DC, Cox RA, Kuruganti U. 1989. Induction of tumor necrosis factor alpha by spherules of Coccidioides immitis. Infect Immun 57:1916–1921.
    121.
    Magee DM, Cox RA. 1995. Roles of gamma interferon and interleukin-4 in genetically determined resistance to Coccidioides immitis. Infect Immun 63:3514–3519.
    122.
    Ampel NM, Nesbit LA, Nguyen CT, Chavez S, Knox KS, Johnson SM, Pappagianis D. 2015. Cytokine profiles from antigen-stimulated whole-blood samples among patients with pulmonary or nonmeningeal disseminated coccidioidomycosis. Clin Vaccine Immunol 22:917–922.
    123.
    Muñoz-Hernández B, Palma-Cortés G, Manjarrez ME. 2012. Innovation of the parasitic cycle of Coccidioides spp.,p 29–52. In Shah MM (ed), Parasitology. IntechOpen, London, United Kingdom. http://www.intechopen.com/books/parasitology/innovation-of-the-parasitic-cycle-of-coccidioides-spp-.
    124.
    Galgiani JN, Isenberg RA, Stevens DA. 1978. Chemotaxigenic activity of extracts from the mycelial and spherule phases of Coccidioides immitis for human polymorphonuclear leukocytes. Infect Immun 21:862–865.
    125.
    Galgiani JN. 1995. Differences in oxidant release by human polymorphonuclear leukocytes produced by stimulation with different phases of Coccidioides immitis. J Infect Dis 172:199–203.
    126.
    Rubin-Bejerano I, Abeijon C, Magnelli P, Grisafi P, Fink GR. 2007. Phagocytosis by human neutrophils is stimulated by a unique fungal cell wall component. Cell Host Microbe 2:55–67.
    127.
    Ampel NM, Bejarano GC, Galgiani JN. 1992. Killing of Coccidioides immitis by human peripheral blood mononuclear cells. Infect Immun 60:4200–4204.
    128.
    Beaman L, Benjamini E, Pappagianis D. 1981. Role of lymphocytes in macrophage-induced killing of Coccidioides immitis in vitro. Infect Immun 34:347–353.
    129.
    Roy RM, Klein BS. 2012. Dendritic cells in antifungal immunity and vaccine design. Cell Host Microbe 11:436–446.
    130.
    Dionne SO, Podany AB, Ruiz YW, Ampel NM, Galgiani JN, Lake DF. 2006. Spherules derived from Coccidioides posadasii promote human dendritic cell maturation and activation. Infect Immun 74:2415–2422.
    131.
    Awasthi S. 2007. Dendritic cell-based vaccine against coccidioides infection. Ann N Y Acad Sci 1111:269–274.
    132.
    Ampel NM. 2007. The complex immunology of human coccidioidomycosis. Ann N Y Acad Sci 1111:245–258.
    133.
    Echols RM, Palmer DL, Long GW. 1982. Tissue eosinophilia in human coccidioidomycosis. Rev Infect Dis 4:656–664.
    134.
    Simons CM, Stratton CW, Kim AS. 2011. Peripheral blood eosinophilia as a clue to the diagnosis of an occult Coccidioides infection. Hum Pathol 42:449–453.
    135.
    Schmidt S, Zimmermann SY, Tramsen L, Koehl U, Lehrnbecher T. 2013. Natural killer cells and antifungal host response. Clin Vaccine Immunol 20:452–458.
    136.
    Schmidt S, Tramsen L, Lehrnbecher T. 2017. Natural killer cells in antifungal immunity. Front Immunol 8:1623.
    137.
    Petkus AF, Baum LL. 1987. Natural killer cell inhibition of young spherules and endospores of Coccidioides immitis. J Immunol 139:3107–3111.
    138.
    Magee DM, Cox RA. 1996. Interleukin-12 regulation of host defenses against Coccidioides immitis. Infect Immun 64:3609–3613.
    139.
    Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie AN, Mebius RE, Powrie F, Vivier E. 2013. Innate lymphoid cells—a proposal for uniform nomenclature. Nat Rev Immunol 13:145–149.
    140.
    Vivier E, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie ANJ, Mebius RE, Powrie F, Spits H. 2018. Innate lymphoid cells: 10 years on. Cell 174:1054–1066.
    141.
    Mindt BC, Fritz JH, Duerr CU. 2018. Group 2 innate lymphoid cells in pulmonary immunity and tissue homeostasis. Front Immunol 9:840.
    142.
    Galgiani JN, Yam P, Petz LD, Williams PL, Stevens DA. 1980. Complement activation by Coccidioides immitis: in vitro and clinical studies. Infect Immun 28:944–949.
    143.
    De Lucca AJ, Walsh TJ. 1999. Antifungal peptides: novel therapeutic compounds against emerging pathogens. Antimicrob Agents Chemother 43:1–11.
    144.
    Ordonez SR, Veldhuizen EJA, van Eijk M, Haagsman HP. 2017. Role of soluble innate effector molecules in pulmonary defense against fungal pathogens. Front Microbiol 8:2098.
    145.
    Nayak A, Dodagatta-Marri E, Tsolaki AG, Kishore U. 2012. An insight into the diverse roles of surfactant proteins, SP-A and SP-D in innate and adaptive immunity. Front Immunol 3:131.
    146.
    Ampel NM, Dionne SO, Giblin A, Podany AB, Galgiani J. 2009. Mannose-binding lectin serum levels are low in persons with clinically active coccidioidomycosis. Mycopathologia 167:173–180.
    147.
    Segal GP, Lehrer RI, Selsted ME. 1985. In vitro effect of phagocyte cationic peptides on Coccidioides immitis. J Infect Dis 151:890–894.
    148.
    Collins MS, Pappagianis D. 1974. Inhibition by lysozyme of growth of the spherule phase of Coccidioides immitis in vitro. Infect Immun 10:616–623.
    149.
    Cox RA, Baker BS, Stevens DA. 1982. Specificity of immunoglobulin E in coccidioidomycosis and correlation with disease involvement. Infect Immun 37:609–616.
    150.
    Smith CE, Whiting EG, Baker EE, Rosenberger HG, Beard RR, Saito MT. 1948. The use of coccidioidin. Am Rev Tuberc 57:330–360.
    151.
    Drutz DJ, Catanzaro A. 1978. Coccidioidomycosis. Part I. Am Rev Respir Dis 117:559–585.
    152.
    Wack EE, Ampel NM, Sunenshine RH, Galgiani JN. 2015. The return of delayed-type hypersensitivity skin testing for coccidioidomycosis. Clin Infect Dis 61:787–791.
    153.
    Zweiman BD, Pappagianis D, Maibach H, Hildreth E. 1969. Coccidioidin delayed hypersensitivity: skin test and in vitro lymphocyte reactivities. J Immunol 102:1284–1289.
    154.
    Stevens DA. 1995. Current concepts: coccidioidomycosis. N Engl J Med 332:1077–1082.
    155.
    Catanzaro A, Spitler LE, Moser KM. 1975. Cellular immune response in coccidioidomycosis. Cell Immunol 15:360–371.
    156.
    Vinh DC, Schwartz B, Hsu AP, Miranda DJ, Valdez PA, Fink D, Lau KP, Long-Priel D, Kuhns DB, Uzel G, Pittaluga S, Hoover S, Galgiani JN, Holland SM. 2011. Interleukin-12 receptor beta1 deficiency predisposing to disseminated coccidioidomycosis. Clin Infect Dis 52:e99–e102.
    157.
    Beaman L, Pappagianis D, Benjamini E. 1977. Significance of T cells in resistance to experimental murine coccidioidomycosis. Infect Immun 17:580–585.
    158.
    Beaman L, Pappagianis D, Benjamini E. 1979. Mechanisms of resistance to infection with Coccidioides immitis in mice. Infect Immun 23:681–685.
    159.
    Casadevall A. 1995. Antibody immunity and invasive fungal infections. Infect Immun 63:4211–4218.
    160.
    Kong Y-C, Savage DC, Levine HB. 1966. Enhancement of immune responses in mice by a booster injection of Coccidioides spherules. J Immunol 95:1048–1056.
    161.
    Ibrahim AB, Pappagianis D. 1973. Experimental induction of anergy to coccidioidin by antigens of Coccidioides immites. Infect Immun 7:786–794.
    162.
    Magee DM, Friedberg RL, Woitaske MD, Johnston SA, Cox RA. 2005. Role of B cells in vaccine-induced immunity against coccidioidomycosis. Infect Immun 73:7011–7013.
    163.
    Hung CY, Gonzalez A, Wuthrich M, Klein BS, Cole GT. 2011. Vaccine immunity to coccidioidomycosis occurs by early activation of three signal pathways of T helper cell response (Th1, Th2, and Th17). Infect Immun 79:4511–4522.
    164.
    Yoshinoya S, Cox RA, Pope RM. 1980. Circulating immune complexes in coccidioidomycosis. Detection and characterization. J Clin Invest 66:655–663.
    165.
    Cox RA, Pope RM. 1987. Serum-mediated suppression of lymphocyte transformation responses in coccidioidomycosis. Infect Immun 55:1058–1062.
    166.
    Brown J, Benedict K, Park BJ, Thompson GR, III. 2013. Coccidioidomycosis: epidemiology. Clin Epidemiol 5:185–197.
    167.
    Stockamp NW, Thompson GR, III. 2016. Coccidioidomycosis. Infect Dis Clin North Am 30:229–246.
    168.
    Willett FM, Weiss A. 1945. Coccidioidomycosis in southern California: report of a new endemic area with a review of 100 cases. Ann Intern Med 23:349–375.
    169.
    Wieden MA, Lundergan LL, Blum J, Delgado KL, Coolbaugh R, Howard R, Peng T, Pugh E, Reis N, Theis J, Galgiani JN. 1996. Detection of coccidioidal antibodies by 33-kDa spherule antigen, Coccidioides EIA, and standard serologic tests in sera from patients evaluated for coccidioidomycosis. J Infect Dis 173:1273–1277.
    170.
    Blair JE, Chang YH, Cheng MR, Vaszar LT, Vikram HR, Orenstein R, Kusne S, Ho S, Seville MT, Parish JM. 2014. Characteristics of patients with mild to moderate primary pulmonary coccidioidomycosis. Emerg Infect Dis 20:983–990.
    171.
    Pappagianis D. 2001. Serologic studies in coccidioidomycosis. Semin Respir Infect 16:242–250.
    172.
    Blair JE, Coakley B, Santelli AC, Hentz JG, Wengenack NL. 2006. Serologic testing for symptomatic coccidioidomycosis in immunocompetent and immunosuppressed hosts. Mycopathologia 162:317–324.
    173.
    Mafi NG, Blair J. 2019. A retrospective evaluation of coccidioidomycosis skin testing in patients with pulmonary coccidioidomycosi in an endemic region, poster 14. In Proceedings of the 63rd Annual Coccidioidomycosis Study Group Meeting.
    174.
    Johnson R, Kernerman SM, Sawtelle BG, Rastogi SC, Nielsen HS, Ampel NM. 2012. A reformulated spherule-derived coccidioidin (Spherusol) to detect delayed-type hypersensitivity in coccidioidomycosis. Mycopathologia 174:353–358.
    175.
    Wheeler C, Lucas KD, Derado G, McCotter O, Tharratt RS, Chiller T, Mohle-Boetani JC. 2018. Risk stratification with coccidioidal skin test to prevent valley fever among inmates, California, 2015. J Correct Health Care 24:342–351.
    176.
    Pappagianis D, Zimmer BL. 1990. Serology of coccidioidomycosis. Clin Microbiol Rev 3:247–268.
    177.
    Maddox SE. 2017. Rapid detection of anti-Coccidioides antibodies using the sonaTM Coccidioides Ab lateral flow assay, p 36. In Proceedings of the Sixty-First Annual Meeting of the Coccidioidomycosis Study Group. Coccidioidomycosis Study Group, Stanford, CA.
    178.
    Donovan FM, Wightman P, Zong Y, Gabe L, Majeed A, Ynosencio T, Bedrick EJ, Galgiani JN. 2019. Delays in coccidioidomycosis diagnosis and associated healthcare utilization in Tucson, Arizona. Emerg Infect Dis 25:1745.
    179.
    Ginn RMR, Bollmann K, Goodsell J, Mendez G, Bradley B, Galgiani JN. 2019. Delays in the diagnosis of coccidioidomycosis and their relationship to healthcare utilization. Emerg Infect Dis.
    180.
    Pu J, Donovan F, Galgiani JN. 2019. Informatic profile of primary care practioners’ testing and managing patients with coccidioidomycosis (cm), p 33. In Proceedings of the 63rd Annual Cocci Study Group meeting, April 5–6, Sacramento, California.
    181.
    Mitchell M, Dizon D, Libke R, Peterson M, Slater D, Dhillon A. 2015. Development of a real-time PCR assay for identification of Coccidioides immitis by use of the BD Max system. J Clin Microbiol 53:926–929.
    182.
    Saubolle MA, Wojack BR, Wertheimer AM, Fuayagem AZ, Young S, Koeneman BA. 2018. Multicenter clinical validation of a cartridge-based real-time PCR system for detection of Coccidioides spp. in lower respiratory specimens. J Clin Microbiol 56:e01277-17.
    183.
    Thompson GR, III, Sharma S, Bays DJ, Pruitt R, Engelthaler DM, Bowers J, Driebe EM, Davis M, Libke R, Cohen SH, Pappagianis D. 2013. Coccidioidomycosis: adenosine deaminase levels, serologic parameters, culture results, and polymerase chain reaction testing in pleural fluid. Chest 143:776–781.
    184.
    Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Geertsma F, Hoover SE, Johnson RH, Kusne S, Lisse J, MacDonald JD, Meyerson SL, Raksin PB, Siever J, Stevens DA, Sunenshine R, Theodore N. 2016. 2016 Infectious Diseases Society of America (IDSA) clinical practice guideline for the treatment of coccidioidomycosis. Clin Infect Dis 63:e112-46.
    185.
    Donovan FM, Zangeneh TT, Malo J, Galgiani JN. 2017. Top questions in the diagnosis and treatment of coccidioidomycosis. Open Forum Infect Dis 4:ofx197.
    186.
    Thompson GR, III, Barker BM, Wiederhold NP. 2017. Large-scale evaluation of in vitro amphotericin B, triazole, and echinocandin activity against Coccidioides species from U.S. institutions. Antimicrob Agents Chemother 61:e02634-16.
    187.
    Ostrosky-Zeichner L, Casadevall A, Galgiani JN, Odds FC, Rex JH. 2010. An insight into the antifungal pipeline: selected new molecules and beyond. Nat Rev Drug Discov 9:719–727.
    188.
    Viriyakosol S, Kapoor M, Okamoto S, Covel J, Soltow QA, Trzoss M, Shaw KJ, Fierer J. 2019. APX001 and other Gwt1 inhibitor prodrugs are effective in experimental Coccidioides immitis pneumonia. Antimicrob Agents Chemother 63:e01715-18.
    189.
    Wiederhold NP, Najvar LK, Jaramillo R, Olivo M, Birch M, Law D, Rex JH, Catano G, Patterson TF. 2018. The orotomide olorofim is efficacious in an experimental model of central nervous system coccidioidomycosis. Antimicrob Agents Chemother 62:e00999-18.
    190.
    Shubitz LF, Roy ME, Trinh HT, Hoekstra WJ, Schotzinger RJ, Garvey EP. 2017. Efficacy of the investigational antifungal VT-1161 in treating naturally occurring coccidioidomycosis in dogs. Antimicrob Agents Chemother 61:e00111-17.

    Author Bios

    Fariba M. Donovan
    Valley Fever Center for Excellence, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    Department of Medicine, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    Fariba M. Donovan, M.D., Ph.D., as both a practicing physician and a research scientist, has long cultivated a particular interest in medical mycology. Her research focuses on the identification of virulence factors and the interaction of several fungi with the human host. She has conducted studies in Coccidioides with the goal of helping in the earlier diagnosis of valley fever to improve patient outcomes, lower costs, and heighten antibiotic stewardship. Additionally, she is developing strategies to study the host innate immune response to Coccidioides with a focus on the early events in coccidioidomycosis.
    Lisa Shubitz
    Valley Fever Center for Excellence, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    Lisa Shubitz, D.V.M., is a research scientist at the Valley Fever Center for Excellence. Her research focus includes developing a vaccine for valley fever and studying the epidemiology of the disease in canines, the ecological distribution of the fungus in southern Arizona, and interactions between the host (both animal and human) and the fungus that causes valley fever, using animal models.
    Daniel Powell
    Valley Fever Center for Excellence, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    Daniel Powell, Ph.D., received his Ph.D. from the University of Baltimore, Baltimore, MD, in 2011 working on immune responses to lipopolysaccharide mutants. Since then, he has conducted research at the University of Arizona. He is a cellular immunologist with interests in vaccine development, as well as early host responses in lung infections.
    Marc Orbach
    Valley Fever Center for Excellence, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    School of Plant Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, Arizona, USA
    Marc Orbach, Ph.D., is a professor of plant pathology in the College of Agriculture and Life Sciences. His focus is based on studying the ecological niche of the fungus that causes valley fever and the analysis of global gene expression in Coccidioides posadasii during both saprobic and parasitic growth. In his analysis, he has been working with the Serial Analysis of Gene Expression (SAGE). His research interests also include the molecular genetics of fungal pathogenicity in animals and plants.
    Jeffrey Frelinger
    Valley Fever Center for Excellence, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    Department of Immunobiology, University of Arizona, Tucson, Arizona, USA
    Jeffrey Frelinger, Ph.D., and the members of his laboratory have been interested for some years in immune responses to the lung pathogens influenza virus and Francisella tularensis. They have begun collaborations on the role of T cell responses in Coccidioides infections and the development of an effective vaccine.
    John N. Galgiani
    Valley Fever Center for Excellence, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    Department of Medicine, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    John N. Galgiani, M.D., has been working with valley fever (coccidioidomycosis) for the last four decades. As director of the Valley Fever Center for Excellence, his passion is research in the treatment of valley fever. This involves studies to improve the detection of the fungus in the environment, to increase the sensitivity of diagnostic tests for patients, and to develop a vaccine to prevent the disease in both humans and animals.

    Information & Contributors

    Information

    Published In

    Clinical Microbiology Reviews
    Volume 33Number 118 December 2019
    eLocator: e00112-19

    History

    Published online: 16 October 2019

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    KEYWORDS

    1. early coccidioidomycosis
    2. early events in valley fever
    3. Coccidioides research
    4. coccidioidomycosis

    Contributors

    Authors

    Fariba M. Donovan
    Valley Fever Center for Excellence, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    Department of Medicine, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    Lisa Shubitz
    Valley Fever Center for Excellence, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    Daniel Powell
    Valley Fever Center for Excellence, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    Marc Orbach
    Valley Fever Center for Excellence, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    School of Plant Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, Arizona, USA
    Jeffrey Frelinger
    Valley Fever Center for Excellence, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    Department of Immunobiology, University of Arizona, Tucson, Arizona, USA
    John N. Galgiani
    Valley Fever Center for Excellence, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA
    Department of Medicine, University of Arizona College of Medicine—Tucson, Tucson, Arizona, USA

    Notes

    Address correspondence to Fariba M. Donovan, [email protected].

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  • Clinical Microbiology ReviewsArticle
    Leprosy in the 21st Century

    SUMMARY

    Despite significant improvements in leprosy (Hansen's disease) treatment and outlook for patients since the introduction of multidrug therapy (MDT) 3 decades ago, the global incidence remains high, and patients often have long-term complications associated with the disease. In this article, we discuss recent findings related to genetics, susceptibility, and disease reservoirs and the implications of these findings for Hansen's disease control and health outcomes for patients. We describe the continued difficulties associated with treatment of inflammatory episodes known as “leprosy reactions,” which cause much of the disability associated with the disease and can affect people for many years after MDT is complete. We also discuss some of the contemporary challenges for physicians and patients, including international and internal migration of people affected by the disease. We suggest some important areas of focus for future Hansen's disease research.

    REFERENCES

    1.
    Walker SL, Lockwood DNJ. 2007. Leprosy. Clin Dermatol 25:165–172.
    2.
    Graham A, Furlong S, Margoles LM, Owusu K, Franco-Paredes C. 2010. Clinical management of leprosy reactions. Infect Dis Clin Pract 18:235–238.
    3.
    Polycarpou A, Walker SL, Lockwood DNJ. 2013. New findings in the pathogenesis of leprosy and implications for the management of leprosy. Curr Opin Infect Dis 26:413–419.
    4.
    Cogen AL, Walker SL, Roberts CH, Hagge DA, Neupane KD, Khadge S, Lockwood DN. 2012. Human beta-defensin 3 is up-regulated in cutaneous leprosy type 1 reactions. PLoS Negl Trop Dis 6:e1869.
    5.
    Degang Y, Akama T, Hara T, Tanigawa K, Ishido Y, Gidoh M, Makino M, Ishii N, Suzuki K. 2012. Clofazimine modulates the expression of lipid metabolism proteins in Mycobacterium leprae-infected macrophages. PLoS Negl Trop Dis 6:e1936.
    6.
    Rambukkana A. 2001. Molecular basis for the peripheral nerve predilection of Mycobacterium leprae. Curr Opin Microbiol 4:21–27.
    7.
    Rambukkana A. 2010. Usage of signaling in neurodegeneration and regeneration of peripheral nerves by leprosy bacteria. Prog Neurobiol 91:102–107.
    8.
    Masaki T, Qu J, Cholewa-Waclaw J, Burr K, Raaum R, Rambukkana A. 2013. Reprogramming adult Schwann cells to stem cell-like cells by leprosy bacilli promotes dissemination of infection. Cell 152:51–67.
    9.
    Britton WJ, Lockwood DNJ. 2004. Leprosy. Lancet 363:1209–1219.
    10.
    Scollard DM. 2008. The biology of nerve injury in leprosy. Lepr Rev 79:242–253.
    11.
    Lockwood DN, Saunderson PR. 2012. Nerve damage in leprosy: a continuing challenge to scientists, clinicians, and service providers. Int Health 4:77–85.
    12.
    Scollard D, Adams LB, Gillis TP, Krahenbuhl JL, Truman RW, Williams DL. 2006. The continuing challenges of leprosy. Clin Microbiol Rev 19:338–381.
    13.
    World Health Organization. 2003. The final push strategy to eliminate leprosy as a public health problem. Questions and answers, 2nd ed. World Health Organization, Geneva, Switzerland.
    14.
    World Health Organization. 2012. Global leprosy situation 2012. Wkly Epidemiol Rec 87:317–328.
    15.
    Robbins G, Tripathy VM, Misra VN, Mohanty RK, Shinde VS, Schug MD. 2009. Ancient skeletal evidence for leprosy in India (2000 B.C.) PLoS One 4:e5669.
    16.
    Schuenemann VJ, Singh P, Mendum TA, Krause-Kyora B, Jäger G, Bos KI, Herbig A, Economou C, Benjak A, Busso P, Nebel A, Boldsen JL, Kjellström A, Wu H, Stewart GR, Taylor GM, Bauer P, Lee OY, Wu HH, Minnikin DE, Besra GS, Tucker K, Roffey S, Sow SO, Cole ST, Nieselt K, Krause J. 2013. Genome-wide comparison of medieval and modern Mycobacterium leprae. Science 341:179–183.
    17.
    Gelber R, Grosset J. 2012. The chemotherapy of leprosy: an interpretive history. Lepr Rev 83:221–240.
    18.
    Sato H, Narita M. 2003. Politics of leprosy segregation in Japan: the emergence, transformation and abolition of the patient segregation policy. Soc Sci Med 56:2529–2539.
    19.
    Han XY, Seo YH, Sizer KC, Schoberle T, May GS, Spencer JS, Li W, Nair RG. 2008. A new Mycobacterium species causing diffuse lepromatous leprosy. Am J Clin Pathol 130:856–864.
    20.
    Vargas-Ocampo F. 2007. Diffuse leprosy of Lucio and Latapí: a histologic study. Lepr Rev 78:248–260.
    21.
    Gillis TP, Scollard DM, Lockwood DNJ. 2011. What is the evidence that the putative Mycobacterium lepromatosis species causes diffuse lepromatous leprosy? Lepr Rev 82:205–209.
    22.
    Woodall P, Scollard D, Rajan L. 2011. Hansen's disease among Micronesian and Marshallese persons living in the United States. Emerg Infect Dis 17:1202.
    23.
    Ridley DS, Jopling WH. 1966. Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis 34:255–273.
    24.
    Ridley DS. 1974. Histological classification and the immunological spectrum of leprosy. Bull World Health Organ 51:451–465.
    25.
    Gupta R, Kar HK, Bharadwaj M. 2012. Revalidation of various clinical criteria for the classification of leprosy—a clinic-pathological study. Lepr Rev 83:354–362.
    26.
    Prasad PVS, Kaviarasan PK. 2010. Leprosy therapy, past and present: can we hope to eliminate it? Indian J Dermatol 55:316–324.
    27.
    Boggild AK, Keystone JS, Kain K. 2004. Leprosy: a primer for Canadian physicians. CMAJ 170:71–78.
    28.
    Brubaker ML, Meyers WM, Bourland J. 1985. Leprosy in children one year of age and under. Int J Lepr Other Mycobact Dis 53:517–523.
    29.
    World Health Organization. 2012. Leprosy: fact sheet no. 101. World Health Organization, Geneva, Switzerland. http://www.who.int/mediacentre/factsheets/fs101/en/.
    30.
    White C. 2002. Sociocultural considerations in the treatment of leprosy in Rio de Janeiro, Brazil 2002. Lepr Rev 73:356–365.
    31.
    Lockwood D, Reid AJC. 2001. The diagnosis of leprosy is delayed in the United Kingdom. QJM 94:207–212.
    32.
    Franco-Paredes C, Jacob JT, Stryjewska B, Yoder L. 2009. Two patients with leprosy and the sudden appearance of inflammation in the skin and new sensory loss. PLoS Negl Trop Dis 3:e425.
    33.
    Moschella S. 2004. An update on the diagnosis and treatment of leprosy. J Am Acad Dermatol 51:417–426.
    34.
    Pocaterra L, Jain S, Reddy R, Muzaffarullah S, Torres O, Suneetha S, Lockwood DN. 2006. Clinical course of erythema nodosum leprosum: an 11-year cohort study in Hyderabad, India. Am J Trop Med Hyg 74:868–879.
    35.
    Rodrigues LC, Lockwood DNJ. 2011. Leprosy now: epidemiology, progress, challenges, and research gaps. Lancet Infect Dis 11:464–470.
    36.
    Lockwood DNJ, Lucas SB, Desikan KV, Ebenezer G, Suneetha S, Nicholls P. 2008. The histological diagnosis of leprosy type 1 reactions: identification of key variables and an analysis of the process of histological diagnosis. J Clin Pathol 61:595–600.
    37.
    Kumar BS, Dogra S, Kaur I. 2004. Epidemiological characteristics of leprosy reactions: 15 years experience from north India. Int J Lepr Other Mycobact Dis 72:125–133.
    38.
    Walker SL, Lockwood DNJ. 2008. Leprosy type 1 (reversal) reactions and their management. Lepr Rev 79:372–386.
    39.
    van Brakel WH, Nicholls PG, Das L, Barkataki P, Suneetha SK, Jadhav RS, Madali P, Lockwood DN, Wilder-Smith E, Desikan KV. 2005. The INFIR cohort study: investigating prediction, detection, and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in North India. Lepr Rev 76:14–34.
    40.
    Kahawita IP, Lockwood DNJ. 2008. Towards understanding the pathology of erythema nodosum leprosum. Trans R Soc Trop Med Hyg 102:329–337.
    41.
    Shinde V, Marcinek P, Rani DS, Sunder SR, Sunder A, Jain S, Arun S, Jain S, Nath I, Kumarasamy T, Velavan TP, Valluri V. 2013. Genetic evidence of TAP1 gene variant as a susceptibility factor in Indian leprosy patients. Hum Immunol 74:803–807.
    42.
    Rajalingam R, Singal DP, Mehra NK. 1997. Transporter associated with antigen-processing (TAP) genes and susceptibility to tuberculoid leprosy and pulmonary tuberculosis. Tissue Antigens 49:168–172.
    43.
    Shaw MA, Donalson IA, Collins A, Peacock CS, Lins-Laison Z, Shaw J, Ramos F, Silveira F, Blackwell JM. 2001. Association and linkage of leprosy phenotypes with HLA class II and tumour necrosis factor genes. Genes Immun 2:196–204.
    44.
    Misch EA, Macdonald M, Ranjit C, Sapkota BR, Wells RD, Siddiqui MR, Kaplan G, Hawn TR. 2008. Human TLR1 deficiency is associated with impaired mycobacterial signaling and protection from leprosy reversal reaction. PLoS Negl Trop Dis 2:e231.
    45.
    Zhang FR, Huang W, Chen SM, Sun LD, Liu H, Li Y, Cui Y, Yan XX, Yang HT, Yang RD, Chu TS, Zhang C, Zhang L, Han JW, Yu GQ, Quan C, Yu YX, Zhang Z, Shi BQ, Zhang LH, Chen H, Wang CY, Lin Y, Zheng HF, Fu XA, Zuo XB, Wang Q, Long H, Sun YP, Cheng YL, Tian HQ, Zhou FS, Liu HX, Lu WS, He SM, Du WL, Shen M, Jin QY, Wang Y, Low HQ, Erwin T, Yang NH, Li JY, Zhao X, Jiao YL, Mao LJ, Yin G, Jiang ZX, Wang XD, Yu YP, Hu ZH, Gong CH, Liu YQ, Liu RY, Wang DM, Wei D, Liu JX, Cao WK, Cao HC, Li YP, Yan WG, Wei SY, Wang KJ, Hibberd ML, Yang S, Zhang XJ, Liu JJ. 2009. Genomewide association study of leprosy. N Engl J Med 361:2609–2618.
    46.
    Berrington WR, Macdonald M, Khadge S, Sapkota BR, Janer M, Hagge DA, Kaplan G, Hawn TR. 2010. Common polymorphisms in the NOD2 gene region are associated with leprosy and its reactive states. J Infect Dis 201:1422–1435.
    47.
    Orlova M, Cobat A, Houng NT, Ba NN, Van Thuc N, Spencer J, Nedelec Y, Barreiro L, Thai VH, Abel L, Alcais A, Schurr E. 2013. Gene set signature of reversal reaction type 1 in leprosy patients. PLoS Genet 9:e1003624.
    48.
    Truman RW, Singh P, Sharma R, Busso P, Rougemont J, Paniz-Mondolfi A, Kapopoulou A, Brisse S, Scollard DM, Gillis TP, Cole ST. 2011. Probable zoonotic leprosy in the southern United States. N Engl J Med 364:1626–1633.
    49.
    Lumpkin LR, III, Cox GF, Wolf JE, Jr. 1983. Leprosy in five armadillo handlers. J Am Acad Dermatol 9:899–903.
    50.
    Abide JM, Webb RM, Jones HL, Young L. 2008. Three indigenous cases of leprosy in the Mississippi delta. South Med J 101:635–638.
    51.
    Deps PD, Alves BL, Gripp CG, Aragao RL, Guedes B, Filho JB, Andreatta MK, Marcari RS, Prates I, Rodrigues LC. 2008. Contact with armadillos increases the risk of leprosy in Brazil: a case control study. Indian J Dermatol Venereol Leprol 74:338–342.
    52.
    Schmitt JV, Dechandt IT, Dopke G, Ribas ML, Cerci FB, Viesi JMZ, Marchioro HZ, Zunino MMB, Miot HA. 2010. Armadillo meat intake was not associated with leprosy in a case control study, Curitiba (Brazil). Mem Inst Oswaldo Cruz 105:857–862.
    53.
    World Health Organization. 2013. WHO multidrug therapy (MDT). World Health Organization, Geneva, Switzerland. http://www.who.int/lep/mdt/en/.
    54.
    White C. 2009. An uncertain cure: living with leprosy in Brazil. Rutgers University Press, New Brunswick, NJ.
    55.
    Nations MK, Lira GV, Catrib AMF. 2009. Stigma, deforming metaphors, and patients' moral experience of multibacillary leprosy in Sobral state, Ceará, Brazil. Cad Saúde Publica 25:1215–1224.
    56.
    Lockwood DN. 2002. Leprosy elimination—a virtual phenomenon or a reality? BMJ 324:1516–1518.
    57.
    Rao PN, Lakshmi TSS. 2005. “Final push of leprosy” in India: what is being pushed? Lepr Rev 71:226–229.
    58.
    Walker SL, Waters MF, Lockwood DN. 2007. The role of thalidomide in the management of erythema nodosum leprosum. Lepr Rev 78:197–215.
    59.
    Ramien ML, Wong A, Keystone JS. 2011. Severe refractory erythema nodosum leprosum successfully treated with the tumor necrosis factor inhibitor etanercept. Clin Infect Dis 52:e133–e135.
    60.
    Faber WR, Jensema AJ, Goldschmidt WFM. 2006. Treatment of recurrent erythema nodosum leprosum with infliximab. N Engl J Med 355:739.
    61.
    Kai M, Nguyen Phuc NH, Nguyen HA, Pham TH, Nguyen KH, Miyamoto Y, Maeda Y, Fukutomi Y, Nakata N, Matsuoka M, Makino M, Nguyen TT. 2011. Analysis of drug-resistant strains of Mycobacterium leprae in an endemic area of Vietnam. Clin Infect Dis 52:e127–e132.
    62.
    Williams DL, Gillis TP. 2004. Molecular detection of drug resistance in Mycobacterium leprae. Lepr Rev 75:118–130.
    63.
    Maeda S, Matsuoka M, Nakata N, Kai M, Maeda Y, Hashimoto K, Kimura H, Kobayashi K, Kashiwabara Y. 2001. Multidrug resistant Mycobacterium leprae from patients with leprosy. Antimicrob Agents Chemother 45:3635–3639.
    64.
    Prober C. 2005. Sixth disease and the ubiquity of human herpesviruses. N Engl J Med 352:753–755.
    65.
    Dreyfus DH. 2013. Herpes viruses and the microbiome. J Allergy Clin Immunol 132:1278–1286.
    66.
    Choi AMK, Ryter SF, Levine B. 2013. Autophagy in human health and disease. N Engl J Med 368:651–661.
    67.
    Levine B, Mizushima N, Virgin HW. 2011. Autophagy in immunity and inflammation. Nature 469:323–333.
    68.
    Willis MS, Patterson C. 2013. Proteotoxicity and cardiac dysfunction—Alzheimer's disease of the heart? N Engl J Med 368:455–464.
    69.
    Cacoub P, Musette P, Descamps B, Meyer O, Speirs C, Finzi L, Rourjeau JC. 2011. The DRESS syndrome: a literature review. Am J Med 124:588–597.
    70.
    Unanue ER. 2007. Viral infections and non-specific protection—good or bad? N Engl J Med 357:1345–1346.
    71.
    World Health Organization. 2012. Social determinants of health: report by the Secretariat. World Health Organization, Geneva, Switzerland. http://www.who.int/social_determinants/B_132_14-en.pdf?ua=1.
    72.
    Barreto JG, De Souza Guimarães L, Leão MRN, Ferreira DVG, Lima RA, Salgado CG. 2011. Anti-PGL-I seroepidemiology in leprosy cases: household contacts and school children from a hyperendemic municipality of the Brazilian Amazon. Lepr Rev 82:358.
    73.
    Rao PS, John AS. 2012. Nutritional status of leprosy patients in India. Indian J Lepr 84:17–22.
    74.
    Bakker M, Hatta M, Kwenang A, Van Mosseveld P, Faber WR, Klatser PR, Oskam L. 2006. Risk factors for developing leprosy—a population-based cohort study in Indonesia. Lepr Rev 77:48–61.
    75.
    Kerr-Pontes LRS, Montenegro ACD, Barreto ML, Werneck GL, Feldmeier H. 2004. Inequality and leprosy in Northeast Brazil: an ecological study. Int J Epidemiol 33:262–269.
    76.
    Kerr-Pontes LRS, Barreto ML, Evangelista CM, Rodrigues LC, Heukelbach J, Feldmeier H. 2006. Socioeconomic, environmental, and behavioural risk factors for leprosy in North-East Brazil: results of a case-control study. Int J Epidemiol 35:994–1000.
    77.
    Murto C, Chammartin F, Schwarz K, da Costa LMM, Kaplan C, Heukelbach J. 2013. Patterns of migration and risks associated with leprosy among migrants in Maranhão, Brazil. PLoS Negl Trop Dis 7:e2422.
    78.
    Penna MLF, Wand-Del-Rey-de-Oliveira ML, Penna G. 2009. Spatial distribution of leprosy in the Amazon region of Brazil. Emerg Infect Dis 15:650–652.
    79.
    Kuhns K. 2012. What's to know? Navigating knowledge gaps of Hansen's disease in the U.S. M.A. thesis. Department of Anthropology, Georgia State University, Atlanta, GA. http://scholarworks.gsu.edu/anthro_theses/66/.
    80.
    Massone C, Nunzi E, Cerroni L. 2010. Histopathologic diagnosis of leprosy in a nonendemic area. Am J Dermatopathol 32:417–419.
    81.
    Rongioletti F, Gallo R, Cozzani E, Parodi A. 2009. Leprosy: a diagnostic trap for dermatopathologists in nonendemic area. Am J Dermatopathol 31:607–610.
    82.
    Jacob JT, Kozarsky P, Dismukes R, Bynoe V, Margoles L, Leonard M, Tellez I, Franco-Paredes C. 2008. Five-year experience with type 1 and type 2 reactions in Hansen disease at a US travel clinic. Am J Trop Med Hyg 79:452–454.
    83.
    De Groot R, Van Brakel WH, De Vries HJ. 2011. Social implications of leprosy in the Netherlands—stigma among ex-leprosy patients in a non-endemic setting. Lepr Rev 82:168–177.
    84.
    White C. 2003. Carville and Curupaiti: experiences of confinement and community. Hist Cien Saude Manguinhos 10:123–141.
    85.
    Staples J. 2007. Peculiar people, amazing lives: leprosy, social exclusion, and community making in South India. Orient Longman Pvt Ltd, New Delhi, India.
    86.
    Barrett R. 2005. Self-mortification and the stigma of leprosy in northern India. Med Anthropol Q 19:216–230.
    87.
    MORHAN. 2005. Consolidated report on the first national seminar on former Hansen's disease colonies. AIFO, Bologna, Italy. http://www.morhan.org.br/views/upload/relatorio_colonias_pdf.pdf.
    88.
    Ebenso B, Fashona A, Ayuba M, Idah M, Adeyemi G, Fada S. 2007. Impact of socio-economic rehabilitation on leprosy stigma in Northern Nigeria: findings of a retrospective study. Asia Pac Disabil Rehabil J 18:98–119.
    89.
    Rocha P. 14 September 2012. Os filhos do preconceito. ISTOÉ Independente 2012(2236). http://www.istoe.com.br/reportagens/237935_OS+FILHOS+DO+PRECONCEITO.
    90.
    Scollard D. 2012. Chemotherapy has changed (almost) everything. Lepr Rev 83:245–246.
    91.
    Moura MLN, Dupnik KM, Sampaio GAA, Nóbrega PFC, Jeronimo AK, do Nascimento-Filho JM, Dantas RLM, Queiroz JW, Barbosa JD, Dias G, Jeronimo SMB. 2013. Active surveillance of Hansen's disease (leprosy): importance for case finding among extra-domiciliary contacts. 2013. PLoS Negl Trop Dis 7:e2093.
    92.
    Reece ST, Ireton G, Mohamath R, Guderian J, Goto W, Gelber R, Groathouse N, Spencer J, Brennan P, Reed S. 2006. ML0405 and ML2331 are antigens of Mycobacterium leprae with potential for diagnosis of leprosy. Clin Vaccine Immunol 13:333–340.
    93.
    Duthie MS, Hay MN, Morales CZ, Carter L, Mohamath R, Ito L, Oyafuso K, Manini MI, Balagon MV, Tan EV, Saunderson PR, Reed SG, Carter D. 2010. Rational design and evaluation of a multiepitope chimeric fusion protein with the potential for leprosy diagnosis. Clin Vaccine Immunol 17:298–303.
    94.
    Duthie MS, Hay MN, Rada EM, Convit J, Ito L, Oyafuso LK, Manini MI, Goulart IM, Lobato J, Goulart LR, Carter D, Reed SG. 2011. Specific IgG antibody responses may be used to monitor leprosy treatment and efficacy and as recurrence prognostic markers. Eur J Clin Microbiol Infect Dis 30:1257–1265.
    95.
    Spencer JS, Duthie MS, Geluk A, Balagon MF, Kim HJ, Wheat WH, Chatterjee D, Jackson M, Li W, Kurihara JN, Maghanoy I, Mallari P, Saunderson P, Brennan PJ, Dockrell HM. 2012. Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy. Mem Inst Oswaldo Cruz 107(Suppl 1):79–89.
    96.
    Infectious Disease Research Institute. 2013. Leprosy 2013: the problem and the solutions. http://www.idri.org/documents/IDRILeprosyGallery.pdf. IDRI, Seattle, WA.
    97.
    Franco-Paredes C, Rouphael N, Del Rio C, Santos-Preciado JI. 2006. Vaccination strategies to prevent tuberculosis in the new millennium: from BCG to new vaccine candidates. Int J Infect Dis 10:93–102.
    98.
    Smith CS, Noordeen SK, Richardus JH, Sansarricq H, Cole ST, Soares RS, Savioli L, Aertsh A, Baruaf S. 2014. A strategy to halt leprosy transmission. Lancet Infect Dis 14:96–97.
    99.
    Lockwood DNJ, Shetty V, Oliveira Penna G. 2014. Hazards of setting targets to eliminate disease: lessons from the leprosy elimination campaign. BMJ 348:g1136.
    100.
    Scollard DM, Joyce MP, Gillis TP. 2006. Development of leprosy and type 1 leprosy reactions after treatment with infliximab: a report of two cases. Clin. Infect. Dis. 43:e19–e22.

    Author Bios

    Cassandra White [email protected]
    Department of Anthropology, Georgia State University, Atlanta, Georgia, USA
    Cassandra White received her B.A. (1991) and M.A. (1993) from the University of Florida and her Ph.D. in Anthropology from Tulane University in 2001. She is an Associate Professor in the Department of Anthropology at Georgia State University in Atlanta, GA, where she has taught for 10 years. She is the author of An Uncertain Cure: Living with Leprosy in Brazil (Rutgers University Press, 2009) and several peer-reviewed articles about Hansen's disease in the United States and Brazil. Her current research focus is on the experience of Hansen's disease and treatment seeking for first-generation Brazilian immigrants to the United States.
    Carlos Franco-Paredes
    Hospital Infantil de México, Federico Gómez, México City, México
    Carlos Franco-Paredes received his M.D. from the La Salle University School of Medicine in México City, México, in 1995. He did his internship and residency in Internal Medicine at Emory University in Atlanta, GA, and received his M.P.H. in International Health from Emory in 2002. He is currently a staff member in the Phoebe Physician Group in southwest Georgia, where he provides consultations in infectious disease and travel medicine. He is also affiliated with the Unidad de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, México, and the Hospital Infantil de México, Federico Gómez, México City, México. He is an Associate Editor of Public Library of Sciences (PLoS) journals (PLoS Neglected Tropical Diseases), and he has 130 publications in peer-reviewed journals. Dr. Franco-Paredes' current research focuses on vaccine-preventable diseases, travel-related vaccines, social determinants of infectious diseases, and neglected tropical diseases.

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    Clinical Microbiology Reviews
    Volume 28Number 1January 2015
    Pages: 80 - 94

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    Cassandra White [email protected]
    Department of Anthropology, Georgia State University, Atlanta, Georgia, USA
    Carlos Franco-Paredes
    Hospital Infantil de México, Federico Gómez, México City, México
    Present address: Carlos Franco-Paredes, Travel Clinic and Infectious Diseases, Phoebe Putney Memorial Hospital, Albany, Georgia, USA.

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    C.W. and C.F.-P. contributed equally to this work.

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  • Clinical Microbiology ReviewsArticle
    Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

    Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

    Abstract

    SUMMARY

    Mucormycosis is a life-threatening fungal infection that occurs in immunocompromised patients. These infections are becoming increasingly common, yet survival remains very poor. A greater understanding of the pathogenesis of the disease may lead to future therapies. For example, it is now clear that iron metabolism plays a central role in regulating mucormycosis infections and that deferoxamine predisposes patients to mucormycosis by inappropriately supplying the fungus with iron. These findings raise the possibility that iron chelator therapy may be useful to treat the infection as long as the chelator does not inappropriately supply the fungus with iron. Recent data support the concept that high-dose liposomal amphotericin is the preferred monotherapy for mucormycosis. However, several novel therapeutic strategies are available. These options include combination therapy using lipid-based amphotericin with an echinocandin or with an azole (largely itraconazole or posaconazole) or with all three. The underlying principles of therapy for this disease remain rapid diagnosis, reversal of underlying predisposition, and urgent surgical debridement.

    REFERENCES

    1.
    Abe, F., H. Inaba, T. Katoh, and M. Hotchi.1990. Effects of iron and desferrioxamine on Rhizopus infection. Mycopathologia110:87-91.
    2.
    Abedi, E., A. Sismanis, K. Choi, and P. Pastore.1984. Twenty-five years' experience treating cerebro-rhino-orbital mucormycosis. Laryngoscope94:1060-1062.
    3.
    Abzug, M. J., and T. J. Walsh.2004. Interferon-gamma and colony-stimulating factors as adjuvant therapy for refractory fungal infections in children. Pediatr. Infect. Dis. J.23:769-773.
    4.
    Adam, R. D., G. Hunter, J. DiTomasso, and G. Comerci, Jr.1994. Mucormycosis: emerging prominence of cutaneous infections. Clin. Infect. Dis.19:67-76.
    5.
    Alsuwaida, K.2002. Primary cutaneous mucormycosis complicating the use of adhesive tape to secure the endotracheal tube. Can. J. Anaesth.49:880-882.
    6.
    Amin, S. B., R. M. Ryan, L. A. Metlay, and W. J. Watson.1998. Absidia corymbifera infections in neonates. Clin. Infect. Dis.26:990-992.
    7.
    Anaissie, E. J., and A. H. Shikhani.1985. Rhinocerebral mucormycosis with internal carotid occlusion: report of two cases and review of the literature. Laryngoscope95:1107-1113.
    8.
    Andrews, D. R., A. Allan, and R. I. Larbalestier.1997. Tracheal mucormycosis. Ann. Thorac. Surg.63:230-232.
    9.
    Artis, W. M., J. A. Fountain, H. K. Delcher, and H. E. Jones.1982. A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability. Diabetes31:1109-1114.
    10.
    Asai, K., K. Suzuki, T. Takahashi, Y. Ito, T. Kazui, and Y. Kita.2003. Pulmonary resection with chest wall removal and reconstruction for invasive pulmonary mucormycosis during antileukemia chemotherapy. Jpn. J. Thorac. Cardiovasc. Surg.51:163-166.
    11.
    Baraia, J., P. Muñoz, J. C. Bernaldo deq Uirós, and E. Bouza.1995. Cutaneous mucormycosis in a heart transplant patient associated with a peripheral catheter. Eur. J. Clin. Microbiol. and Infect. Dis.14:813-815.
    12.
    Bearer, E. A., P. R. Nelson, M. Y. Chowers, and C. E. Davis.1994. Cutaneous zygomycosis caused by Saksenaea vasiformis in a diabetic patient. J. Clin. Microbiol.32:1823-1824.
    13.
    Blin, N., N. Morineau, F. Gaillard, O. Morin, N. Milpied, J. L. Harousseau, and P. Moreau.2004. Disseminated mucormycosis associated with invasive pulmonary aspergillosis in a patient treated for post-transplant high-grade non-Hodgkin's lymphoma. Leukemia Lymphoma45:2161-2163.
    14.
    Blitzer, A., and W. Lawson.1993. Fungal infections of the nose and paranasal sinuses. Part I. Otolaryngol. Clin. North Am.26:1007-1035.
    15.
    Boelaert, J. R., M. de Locht, J. Van Cutsem, V. Kerrels, B. Cantinieaux, A. Verdonck, H. W. Van Landuyt, and Y. J. Schneider.1993. Mucormycosis during deferoxamine therapy is a siderophore-mediated infection. In vitro and in vivo animal studies. J. Clin. Investig.91:1979-1986.
    16.
    Boelaert, J. R., J. Van Cutsem, M. de Locht, Y. J. Schneider, and R. R. Crichton.1994. Deferoxamine augments growth and pathogenicity of Rhizopus, while hydroxypyridinone chelators have no effect. Kidney Int.45:667-671.
    17.
    Bouchara, J. P., N. A. Oumeziane, J. C. Lissitzky, G. Larcher, G. Tronchin, and D. Chabasse.1996. Attachment of spores of the human pathogenic fungus Rhizopus oryzae to extracellular matrix components. Eur. J. Cell Biol.70:76-83.
    18.
    Boyd, A. S., B. Wiser, H. H. Sams, and L. E. King.2003. Gangrenous cutaneous mucormycosis in a child with a solid organ transplant: a case report and review of the literature. Pediatr. Dermatol.20:411-415.
    19.
    Brullet, E., X. Andreu, J. Elias, J. Roig, and M. Cervantes.1993. Gastric mucormycosis in a patient with acquired immunodeficiency syndrome [letter]. Gastrointestinal Endosc.39:106-107.
    20.
    Bullock, J. D., L. M. Jampol, and A. J. Fezza.1974. Two cases of orbital phycomycosis with recovery. Am. J. Ophthalmol.78:811-815.
    21.
    Cagatay, A. A., S. S. Oncu, S. S. Calangu, T. T. Yildirmak, H. H. Ozsut, and H. H. Eraksoy.2001. Rhinocerebral mucormycosis treated with 32 gram liposomal amphotericin B and incomplete surgery: a case report. BMC Infect. Dis.1:22.
    22.
    Chassaing, N., L. Valton, M. Kany, E. Bonnet, E. Uro-Coste, M. B. Delisle, P. Bousquet, and G. Geraud.2003. [Rhino-cerebral fungal infection successfully treated with supplementary hyperbaric oxygen therapy]. Rev. Neurol. (Paris)159:1178-1180.
    23.
    Chinn, R. Y., and R. D. Diamond.1982. Generation of chemotactic factors by Rhizopus oryzae in the presence and absence of serum: relationship to hyphal damage mediated by human neutrophils and effects of hyperglycemia and ketoacidosis. Infect. Immun.38:1123-1129.
    24.
    Cohen-Abbo, A., P. M. Bozeman, and C. C. Patrick.1993. Cunninghamella infections: review and report of two cases of Cunninghamella pneumonia in immunocompromised children. Clin. Infect. Dis.17:173-177.
    25.
    Connor, B. A., R. J. Anderson, and J. W. Smith.1979. Mucor mediastinitis. Chest75:524-526.
    26.
    Couch, L., F. Theilen, and J. T. Mader.1988. Rhinocerebral mucormycosis with cerebral extension successfully treated with adjunctive hyperbaric oxygen therapy. Arch. Otolaryngol. Head Neck Surg.114:791-794.
    27.
    Craig, N. M., F. L. Lueder, J. M. Pensler, B. S. Bean, M. L. Petrick, R. B. Thompson, and L. R. Eramo.1994. Disseminated Rhizopus infection in a premature infant. Pediatr. Dermatol.11:346-350.
    28.
    Dannaoui, E., J. F. Meis, D. Loebenberg, and P. E. Verweij.2003. Activity of posaconazole in treatment of experimental disseminated zygomycosis. Antimicrob. Agents Chemother.47:3647-3650.
    29.
    Dannaoui, E., J. Meletiadis, J. W. Mouton, J. F. Meis, and P. E. Verweij.2003. In vitro susceptibilities of zygomycetes to conventional and new antifungals. J. Antimicrob. Chemother.51:45-52.
    30.
    de Locht, M., J. R. Boelaert, and Y. J. Schneider.1994. Iron uptake from ferrioxamine and from ferrirhizoferrin by germinating spores of Rhizopus microsporus. Biochem. Pharmacol.47:1843-1850.
    31.
    Del Poeta, M., W. A. Schell, and J. R. Perfect.1997. In vitro antifungal activity of pneumocandin L-743,872 against a variety of clinically important molds. Antimicrob. Agents Chemother.41:1835-1836.
    32.
    Dhiwakar, M., A. Thakar, and S. Bahadur.2003. Improving outcomes in rhinocerebral mucormycosis-early diagnostic pointers and prognostic factors. J. Laryngol Otol.117:861-865.
    33.
    Diamond, R. D., C. C. Haudenschild, and N. F. Erickson 3rd.1982. Monocyte-mediated damage to Rhizopus oryzae hyphae in vitro. Infect. Immun.38:292-297.
    34.
    Diekema, D. J., S. A. Messer, R. J. Hollis, R. N. Jones, and M. A. Pfaller.2003. Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J. Clin. Microbiol.41:3623-3626.
    35.
    Diven, S. C., C. A. Angel, H. K. Hawkins, J. L. Rowen, and K. E. Shattuck.2004. Intestinal zygomycosis due to Absidia corymbifera mimicking necrotizing enterocolitis in a preterm neonate. J. Perinatol.24:794-796.
    36.
    Eisen, D. P., and J. Robson.2004. Complete resolution of pulmonary Rhizopus oryzae infection with itraconazole treatment: more evidence of the utility of azoles for zygomycosis. Mycoses47:159-162.
    37.
    Eiser, A. R., R. F. Slifkin, and M. S. Neff.1987. Intestinal mucormycosis in hemodialysis patients following deferoxamine. Am. J. Kidney Dis.10:71-73.
    38.
    Ericsson, M., M. Anniko, H. Gustafsson, C. A. Hjalt, R. Stenling, and A. Tärnvik.1993. A case of chronic progressive rhinocerebral mucormycosis treated with liposomal amphotericin B and surgery [letter]. Clin. Infect. Dis.16:585-586.
    39.
    Espinel-Ingroff, A.1998. Comparison of In vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts. J. Clin. Microbiol.36:2950-2956.
    40.
    Fatterpekar, G., S. Mukherji, A. Arbealez, S. Maheshwari, and M. Castillo.1999. Fungal diseases of the paranasal sinuses. Semin. Ultrasound CT MR20:391-401.
    41.
    Fujii, T., N. Takata, S. Katsutani, and A. Kimura.2003. Disseminated mucormycosis in an acquired immunodeficiency syndrome (AIDS) patient. Intern. Med.42:129-130.
    42.
    Garcia-Covarrubias, L., D. M. Barratt, R. Bartlett, and K. Van Meter.2004. [Treatment of mucormycosis with adjunctive hyperbaric oxygen: five cases treated at the same institution and review of the literature]. Rev. Investig. Clin.56:51-55.
    43.
    Gartenberg, G., E. J. Bottone, G. T. Keusch, and I. Weitzman.1978. Hospital-acquired mucormycosis (Rhizopus rhizopodiformis) of skin and subcutaneous tissue: epidemiology, mycology and treatment. N. Engl. J. Med.299:1115-1118.
    44.
    Gil-Lamaignere, C., M. Simitsopoulou, E. Roilides, A. Maloukou, R. M. Winn, and T. J. Walsh.2005. Interferon-gamma and granulocyte-macrophage colony-stimulating factor augment the activity of polymorphonuclear leukocytes against medically important zygomycetes. J Infect. Dis.191:1180-1187.
    45.
    Gleissner, B., A. Schilling, I. Anagnostopolous, I. Siehl, and E. Thiel.2004. Improved outcome of zygomycosis in patients with hematological diseases? Leukemia Lymphoma45:1351-1360.
    46.
    Goodill, J. J., and J. G. Abuelo.1987. Mucormycosis-a new risk of deferoxamine therapy in dialysis patients with aluminum or iron overload? [letter]. N. Engl. J. Med.317:54.
    47.
    Groll, A. H., N. Giri, V. Petraitis, R. Petraitiene, M. Candelario, J. S. Bacher, S. C. Piscitelli, and T. J. Walsh.2000. Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system. J. Infect. Dis.182:274-282.
    48.
    Guevara, N., D. Roy, C. Dutruc-Rosset, J. Santini, P. Hofman, and L. Castillo.2004. Mucormycosis-early diagnosis and treatment. Rev. Laryngol. Otol. Rhinol. (Bord)125:127-131.
    49.
    Harada, M., T. Manabe, K. Yamashita, and N. Okamoto.1992. Pulmonary mucormycosis with fatal massive hemoptysis. Acta Pathol. Jpn.42:49-55.
    50.
    Harper, J. J., C. Coulter, G. R. Lye, and G. R. Nimmo.1996. Rhizopus and tongue depressors [letter; comment]. Lancet348:1250.
    51.
    Helenglass, G., J. A. Elliott, and N. P. Lucie.1981. An unusual presentation of opportunistic mucormycosis. Br. Med. J. (Clin. Res. ed.)282:108-109.
    52.
    Herbrecht, R., D. W. Denning, T. F. Patterson, J. E. Bennett, R. E. Greene, J. W. Oestmann, W. V. Kern, K. A. Marr, P. Ribaud, O. Lortholary, R. Sylvester, R. H. Rubin, J. R. Wingard, P. Stark, C. Durand, D. Caillot, E. Thiel, P. H. Chandrasekar, M. R. Hodges, H. T. Schlamm, P. F. Troke, and B. de Pauw.2002. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N. Engl. J. Med.347:408-415.
    53.
    Hofman, V., L. Castillo, F. Betis, N. Guevara, M. Gari-Toussaint, and P. Hofman.2003. Usefulness of frozen section in rhinocerebral mucormycosis diagnosis and management. Pathology35:212-216.
    54.
    Holzel, H., S. Macqueen, A. MacDonald, S. Alexander, C. K. Campbell, E. M. Johnson, and D. W. Warnock.1998. Rhizopus microsporus in wooden tongue depressors: a major threat or minor inconvenience? J. Hosp. Infect.38:113-118.
    55.
    Hosseini, M., and J. Lee.1998. Gastrointestinal mucormycosis mimicking ischemic colitis in a patient with systemic lupus erythematosus. Am. J. Gastroenterol.93:1360-1362.
    56.
    Hotchi, M., M. Okada, and T. Nasu.1980. Present state of fungal infections in autopsy cases in Japan. Am. J. Clin. Pathol.74:410-416.
    57.
    Husain, S., B. D. Alexander, P. Munoz, R. K. Avery, S. Houston, T. Pruett, R. Jacobs, E. A. Dominguez, J. G. Tollemar, K. Baumgarten, C. M. Yu, M. M. Wagener, P. Linden, S. Kusne, and N. Singh.2003. Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi. Clin. Infect. Dis.37:221-229.
    58.
    Hussain, S., N. Salahuddin, I. Ahmad, I. Salahuddin, and R. Jooma.1995. Rhinocerebral invasive mycosis: occurrence in immunocompetent individuals. Eur. J. Radiol.20:151-155.
    59.
    Ibrahim, A. S., V. Avanessian, B. Spellberg, and J. E. Edwards, Jr.2003. Liposomal amphotericin B, and not amphotericin B deoxycholate, improves survival of diabetic mice infected with Rhizopus oryzae. Antimicrob. Agents Chemother.47:3343-3344.
    60.
    Ibrahim, A. S., J. C. Bowman, V. Avanessian, K. Brown, B. Spellberg, J. J. Edwards, and C. M. Douglas.2005. Caspofungin inhibits Rhizopus oryzae 1,3-d-glucan synthase, lowers quantitative PCR-measured brain burden, and improves survival at a low but not a high dose during murine disseminated zygomycosis. Antimicrob. Agents Chemother. 49:721-727.
    61.
    Ibrahim, A. S., J. E. J. Edwards, and S. G. Filler.2003. Zygomycosis, p. 241-251. In W. E. Dismukes, P. G. Pappas, and J. D. Sobel (ed.), Clinical mycology. Oxford University Press, New York, N.Y.
    62.
    Ibrahim, A. S., S. Klein, H. Lee, Y. Fu, H. Waskin, and J. Edwards, Jr.2000. Presented at the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, Canada.
    63.
    Ibrahim, A. S., B. Spellberg, V. Avanessian, Y. Fu, and J. E. Edwards.2005. Rhizopus oryzae adheres to, is phagocytosed by, and damages endothelial cells in vitro. Infect. Immun. 73:778-783.
    64.
    Ibrahim, A. S., B. Spellberg, V. Avanessian, Y. Fu, and J. E. Edwards, Jr.2005. Rhizopus oryzae adheres to, is phagocytosed by, and damages endothelial cells in vitro. Infect Immun73:778-783.
    65.
    Ide, L., I. Buysschaert, H. Demuynck, R. De Man, A. Verlinde, E. De Laere, and I. Surmont.2004. Zygomycosis in neutropenic patients with past Aspergillus infection: a role for posaconazole? Clin. Microbiol. Infect.10:862-863.
    66.
    Imhof, A., S. A. Balajee, D. N. Fredricks, J. A. Englund, and K. A. Marr.2004. Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole. Clin. Infect. Dis.39:743-746.
    67.
    Jacobs, P., L. Wood, A. Du Toit, and K. Esterhuizen.2003. Eradication of invasive mucormycosis-effectiveness of the Echinocandin FK463. Hematology8:119-123.
    68.
    Kamalam, A., and A. S. Thambiah.1980. Cutaneous infection by Syncephalastrum. Sabouraudia18:19-20.
    69.
    Kauffman, C. A.2004. Zygomycosis: reemergence of an old pathogen. Clin. Infect. Dis.39:588-590.
    70.
    Kawakami, K., Y. Watanabe, and S. Kadowaki.2004. [Early onset invasive pulmonary zygomycosis following allogeneic peripheral blood stem cell transplantation in a patient with therapy-related myelodysplastic syndrome]. Rinsho Ketsueki45:319-321.
    71.
    Kecskes, S., G. Reynolds, and G. Bennett.1997. Survival after gastrointestinal mucormycosis in a neonate. J. Paediatr. Child Health33:356-359.
    72.
    Kemna, M. E., R. C. Neri, R. Ali, and I. F. Salkin.1994. Cokeromyces recurvatus, a mucoraceous zygomycete rarely isolated in clinical laboratories. J. Clin. Microbiol.32:843-845.
    73.
    Kerr, O. A., C. Bong, C. Wallis, and M. J. Tidman.2004. Primary cutaneous mucormycosis masquerading as pyoderma gangrenosum. Br. J. Dermatol.150:1212-1213.
    74.
    Khardori, N., S. Hayat, K. Rolston, and G. P. Bodey.1989. Cutaneous Rhizopus and Aspergillus infections in five patients with cancer. Arch. Dermatol.125:952-956.
    75.
    Khor, B. S., M. H. Lee, H. S. Leu, and J. W. Liu.2003. Rhinocerebral mucormycosis in Taiwan. J. Microbiol. Immunol. Infect.36:266-269.
    76.
    Kline, M. W.1985. Mucormycosis in children: review of the literature and report of cases. Pediatr. Infect. Dis.4:672-676.
    77.
    Knoop, C., M. Antoine, J. L. Vachiéry, G. Depré, C. Alonso-Vega, M. Struelens, J. L. Van Laethem, P. Lingier, N. Nagy, F. Jacobs, M. R. Kramer, and M. Estenne.1998. Gastric perforation due to mucormycosis after heart-lung and heart transplantation. Transplant.66:932-935.
    78.
    Kontoyianis, D. P., S. Vartivarian, E. J. Anaissie, G. Samonis, G. P. Bodey, and M. Rinaldi.1994. Infections due to Cunninghamella bertholletiae in patients with cancer: report of three cases and review. Clin. Infect. Dis.18:925-928.
    79.
    Kontoyiannis, D. P., V. C. Wessel, G. P. Bodey, and K. V. Rolston.2000. Zygomycosis in the 1990s in a tertiary-care cancer center. Clin. Infect. Dis.30:851-856.
    80.
    Kordy, F. N., I. Z. Al-Mohsen, F. Hashem, E. Almodovar, S. Al Hajjar, and T. J. Walsh.2004. Successful treatment of a child with posttraumatic necrotizing fasciitis caused by Apophysomyces elegans: case report and review of literature. Pediatr. Infect. Dis. J.23:877-879.
    81.
    Kwon-Chung, K. J., and J. E. Bennett.1992. Medical mycology, p. 524-559. Lea & Febiger, Philadelphia, Pa.
    82.
    Kwon-Chung, K. J., R. C. Young, and M. Orlando.1975. Pulmonary mucormycosis caused by Cunninghamella elegans in a patient with chronic myelogenous leukemia. Am. J. Clin. Pathol.64:544-548.
    83.
    Larsen, K., C. von Buchwald, B. Ellefsen, and D. Francis.2003. Unexpected expansive paranasal sinus mucormycosis. ORL J. Otorhinolaryngol. Relat. Spec.65:57-60.
    84.
    LeCompte, P. M., and W. A. Miessner.1947. Mucormycosis of the central nervous system associated with hemochromatosis. Am. J. Pathol.23:673-676.
    85.
    Lee, F. Y., S. B. Mossad, and K. A. Adal.1999. Pulmonary mucormycosis: the last 30 years. Arch. Intern. Med.159:1301-1309.
    86.
    Leong, A. S. Y.1978. Granulomatous mediastinitis due to Rhizopus species. Am. J. Clin. Pathol.70:103-107.
    87.
    Leong, K. W., B. Crowley, B. White, G. M. Crotty, D. S. O'Briain, C. Keane, and S. R. McCann.1997. Cutaneous mucormycosis due to Absidia corymbifera occurring after bone marrow transplantation. Bone Marrow Transplant.19:513-515.
    88.
    Lowe, J. T., Jr., and W. R. Hudson.1975. Rhincerebral phycomycosis and internal carotid artery thrombosis. Arch. Otolaryngol.101:100-103.
    89.
    Lye, G. R., G. Wood, and G. Nimmo.1996. Subcutaneous zygomycosis due to Saksenaea vasiformis: rapid isolate identification using a modified sporulation technique. Pathology28:364-365.
    90.
    Maertens, J., H. Demuynck, E. K. Verbeken, P. Zachée, G. E. Verhoef, P. Vandenberghe, and M. A. Boogaerts.1999. Mucormycosis in allogeneic bone marrow transplant recipients: report of five cases and review of the role of iron overload in the pathogenesis. Bone Marrow Transplant.24:307-312.
    91.
    Maliwan, N., C. V. Reyes, and J. W. Rippon.1984. Osteomyelitis secondary to cutaneous mucormycosis. Report of a case and a review of the literature. Am. J. Dermatopathol.6:479-481.
    92.
    Maravi-Poma, E., J. L. Rodriguez-Tudela, J. G. de Jalon, A. Manrique-Larralde, L. Torroba, J. Urtasun, B. Salvador, M. Montes, E. Mellado, F. Rodriguez-Albarran, and A. Pueyo-Royo.2004. Outbreak of gastric mucormycosis associated with the use of wooden tongue depressors in critically ill patients. Intensive Care Med.30:724-728.
    93.
    Marchevsky, A. M., E. J. Bottone, S. A. Geller, and D. K. Giger.1980. The changing spectrum of disease, etiology, and diagnosis of mucormycosis. Hum. Pathol.11:457-464.
    94.
    Marr, K. A., R. A. Carter, F. Crippa, A. Wald, and L. Corey.2002. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin. Infect. Dis.34:909-917.
    95.
    Martinez, E. J., M. R. Cancio, J. T. t. Sinnott, A. L. Vincent, and S. G. Brantley.1997. Nonfatal gastric mucormycosis in a renal transplant recipient. South. Medical J.90:341-344.
    96.
    Marty, F. M., L. A. Cosimi, and L. R. Baden.2004. Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N. Engl. J. Med.350:950-952.
    97.
    Mazza, D., J. Gugenheim, E. Baldini, and J. Mouiel.1999. Gastrointestinal mucormycosis and liver transplantation; a case report and review of the literature [letter]. Transplant. Int.12:297-298.
    98.
    McAdams, H. P., M. Rosado de Christenson, D. C. Strollo, and E. F. Patz, Jr.1997. Pulmonary mucormycosis: radiologic findings in 32 cases. AJR Am. J. Roentgenol.168:1541-1548.
    99.
    McNulty, J. S.1982. Rhinocerebral mucormycosis: predisposing factors. Laryngoscope92:1140-1143.
    100.
    Mead, J. H., G. P. Lupton, C. L. Dillavou, and R. B. Odom.1979. Cutaneous Rhizopus infection. Occurrence as a postoperative complication associated with an elasticized adhesive dressing. JAMA242:272-274.
    101.
    Mori, T., M. Egashira, N. Kawamata, K. Oshimi, K. Nakamura, T. Oguri, H. Aida, A. Hiruma, and M. Ichinohe.2003. Zygomycosis: two case reports and review of reported cases in the literature in Japan. Nippon Ishinkin Gakkai Zasshi44:163-179.
    102.
    Morrison, V. A., and P. B. McGlave.1993. Mucormycosis in the BMT population. Bone Marrow Transplant.11:383-388.
    103.
    Murray, H. W.1975. Pulmonary mucormycosis with massive fatal hemoptysis. Chest68:65-68.
    104.
    Mutsukura, K., Y. Tsuboi, A. Imamura, F. Fujiki, and T. Yamada.2004. [Garcin syndrome in a patient with rhinocerebral mucormycosis]. No To Shinkei56:231-235.
    105.
    Nagy-Agren, S. E., P. Chu, G. J. Smith, H. A. Waskin, and F. L. Altice.1995. Zygomycosis (mucormycosis) and HIV infection: report of three cases and review. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol.10:441-449.
    106.
    Nissen, M. D., A. K. Jana, M. J. Cole, J. M. Grierson, and G. L. Gilbert.1999. Neonatal gastrointestinal mucormycosis mimicking necrotizing enterocolitis. Acta Paediatr.88:1290-1293.
    107.
    Nithyanandam, S., M. S. Jacob, R. R. Battu, R. K. Thomas, M. A. Correa, and O. D'Souza.2003. Rhino-orbito-cerebral mucormycosis. A retrospective analysis of clinical features and treatment outcomes. Indian J. Ophthalmol.51:231-236.
    108.
    Nussbaum, E. S., and W. A. Hall.1994. Rhinocerebral mucormycosis: changing patterns of disease. Surg. Neurol.41:152-156.
    109.
    O'Brien, T. J., and P. McKelvie.1994. Rhinocerebral mucormycosis presenting as periorbital cellulitis with blindness: report of 2 cases. Clin. Exp. Neurol.31:68-78.
    110.
    Ogunlana, E. O.1975. Fungal air spora at Ibadan, Nigeria. Appl. Microbiol.29:458-463.
    111.
    Oliver, M. R., W. C. Van Voorhis, M. Boeckh, D. Mattson, and R. A. Bowden.1996. Hepatic mucormycosis in a bone marrow transplant recipient who ingested naturopathic medicine. Clin. Infect. Dis.22:521-524.
    112.
    Oren, I.2005. Breakthrough zygomycosis during empirical voriconazole therapy in febrile patients with neutropenia. Clin. Infect. Dis.40:770-771.
    113.
    Pagano, L., P. Ricci, A. Nosari, A. Tonso, M. Buelli, M. Montillo, L. Cudillo, A. Cenacchi, C. Savignana, and L. Melillo.1995. Fatal haemoptysis in pulmonary filamentous mycosis: an underevaluated cause of death in patients with acute leukaemia in haematological complete remission. A retrospective study and review of the literature. Gimema Infection Program (Gruppo Italiano Malattie Ematologiche dell'Adulto). Br. J. Haematol.89:500-505.
    114.
    Parfrey, N. A.1986. Improved diagnosis and prognosis of mucormycosis. A clinicopathologic study of 33 cases. Medicine65:113-123.
    115.
    Patiño, J. F., and D. Castro.1991. Necrotizing lesions of soft tissues: a review. World J. Surg.15:235-239.
    116.
    Pavie, J., M. Lafaurie, C. Lacroix, A. Marie Zagdanski, D. Debrosse, G. Socie, F. Derouin, E. Gluckman, and J. Michel Molina.2004. Successful treatment of pulmonary mucormycosis in an allogenic bone-marrow transplant recipient with combined medical and surgical therapy. Scand. J. Infect. Dis.36:767-769.
    117.
    Perfect, J. R., K. A. Marr, T. J. Walsh, R. N. Greenberg, B. DuPont, J. de la Torre-Cisneros, G. Just-Nubling, H. T. Schlamm, I. Lutsar, A. Espinel-Ingroff, and E. Johnson.2003. Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin. Infect. Dis.36:1122-1131.
    118.
    Peterson, K. L., M. Wang, R. F. Canalis, and E. Abemayor.1997. Rhinocerebral mucormycosis: evolution of the disease and treatment options. Laryngoscope107:855-862.
    119.
    Petrikkos, G., A. Skiada, H. Sambatakou, A. Toskas, G. Vaiopoulos, M. Giannopoulou, and N. Katsilambros.2003. Mucormycosis: ten-year experience at a tertiary-care center in Greece. Eur. J. Clin. Microbiol. Infect. Dis.22:753-756.
    120.
    Pfaller, M. A., S. A. Messer, R. J. Hollis, and R. N. Jones.2002. Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Program, 2000. Antimicrob. Agents Chemother.46:1032-1037.
    121.
    Pierce, P. F., M. B. Wood, G. D. Roberts, R. H. Fitzgerald, Jr., C. Robertson, and R. S. Edson.1987. Saksenaea vasiformis osteomyelitis. J. Clin. Microbiol.25:933-935.
    122.
    Pillsbury, H. C., and N. D. Fischer.1977. Rhinocerebral mucormycosis. Arch. Otolaryngol.103:600-604.
    123.
    Ponz, E., J. M. Campistol, T. Ribalta, J. Montoliú, J. Ramírez, J. Almirall, and L. Revert.1991. [Disseminated mucormycosis in a hemodialyzed female patient treated with deferoxamine]. Rev. Clin. Espanol.188:85-87.
    124.
    Prasad, R. M., S. M. Bose, K. Vaiphei, and G. R. Verma.2003. Post operative abdominal wall mucormycosis mimicking as bacterial necrotising fasciitis. J. Postgrad. Med.49:187-188.
    125.
    Quinio, D., A. Karam, J. P. Leroy, M. C. Moal, B. Bourbigot, O. Masure, B. Sassolas, and A. M. Le Flohic.2004. Zygomycosis caused by Cunninghamella bertholletiae in a kidney transplant recipient. Med. Mycol.42:177-180.
    126.
    Rees, J. R., R. W. Pinner, R. A. Hajjeh, M. E. Brandt, and A. L. Reingold.1998. The epidemiological features of invasive mycotic infections in the San Francisco Bay area, 1992-1993: results of population-based laboratory active surveillance. Clin. Infect. Dis.27:1138-1147.
    127.
    Reid, V. J., D. L. Solnik, T. Daskalakis, and K. P. Sheka.2004. Management of bronchovascular mucormycosis in a diabetic: a surgical success. Ann. Thorac. Surg.78:1449-1451.
    128.
    Reimund, E., and A. Ramos.1994. Disseminated neonatal gastrointestinal mucormycosis: a case report and review of the literature. Pediatr. Pathol.14:385-389.
    129.
    Ribes, J. A., C. L. Vanover-Sams, and D. J. Baker.2000. Zygomycetes in human disease. Clin. Microbiol. Rev.13:236-301.
    130.
    Rickerts, V., A. Bohme, and G. Just-Nubling.2002. Risk factor for invasive zygomycosis in patients with hematologic malignancies. Mycoses45(Suppl. 1):27-30.
    131.
    Robb, S. M.1966. Reactions of fungi to exposure to 10 atmospheres pressure of oxygen. J. Gen. Microbiol.45:17-29.
    132.
    Rothstein, R. D., and G. L. Simon.1986. Subacute pulmonary mucormycosis. J. Med. Vet. Mycol.24:391-394.
    133.
    Safdar, A., S. O'Brien, and I. F. Kouri.2004. Efficacy and feasibility of aerosolized amphotericin B lipid complex therapy in caspofungin breakthrough pulmonary zygomycosis. Bone Marrow Transplant.34:467-468.
    134.
    Santos, J., P. Espigado, C. Romero, J. Andreu, A. Rivero, and J. A. Pineda.1994. Isolated renal mucormycosis in two AIDS patients. Eur. J. Clin. Microbiol. Infect. Dis.13:430-432.
    135.
    Sehgal, A., M. Raghavendran, D. Kumar, A. Srivastava, D. Dubey, and A. Kumar.2004. Rhinocerebral mucormycosis causing basilar artery aneurysm with concomitant fungal colonic perforation in renal allograft recipient: a case report. Transplantation78:949-950.
    136.
    Serna, J. H., A. Wanger, and A. K. Dosekun.2003. Successful treatment of mucormycosis peritonitis with liposomal amphotericin B in a patient on long-term peritoneal dialysis. Am. J. Kidney Dis.42:E14-17.
    137.
    Sharma, M. C., S. S. Gill, S. Kashyap, R. Kataria, D. K. Gupta, P. Sahni, and S. K. Acharya.1998. Gastrointestinal mucormycosis-an uncommon isolated mucormycosis. Indian J. Gastroenterol.17:131-133.
    138.
    Singh, N., T. Gayowski, J. Singh, and V. L. Yu.1995. Invasive gastrointestinal zygomycosis in a liver transplant recipient: case report and review of zygomycosis in solid-organ transplant recipients. Clin. Infect. Dis.20:617-620.
    139.
    Siu, K. L., and W. H. Lee.2004. A rare cause of intestinal perforation in an extreme low birth weight infant-gastrointestinal mucormycosis: a case report. J. Perinatol.24:319-321.
    140.
    Siwek, G. T., K. J. Dodgson, M. de Magalhaes-Silverman, L. A. Bartelt, S. B. Kilborn, P. L. Hoth, D. J. Diekema, and M. A. Pfaller.2004. Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis. Clin. Infect. Dis.39:584-587.
    141.
    Spellberg, B., Y. Fu, J. Edwards Jr., and A. S. Ibrahim.2005. Combination therapy with amphotericin B lipid complex and caspofungin acetate of disseminated zygomycosis in diabetic ketoacidotic mice. Antimicrob. Agents Chemother.49:830-832.
    142.
    Spellberg, B., M. D. Witt, and C. K. Beck.2004. Amphotericin B: is a lipid-formulation gold standard feasible? Clin. Infect. Dis.38:304-307.
    143.
    Sponsler, T. A., J. W. Sassani, L. N. Johnson, and J. Towfighi.1992. Ocular invasion in mucormycosis. Survey Ophthalmol.36:345-350.
    144.
    Straatsma, B. R., L. E. Zimmerman, and J. D. M. Gass.1962. Phycomycosis: a clinicopathologic study of fifty-one cases. Lab. Investig.11:963-985.
    145.
    Sugar, A. M.2005. Agents of mucormycosis and related species, p. 2979. In G. L. Mandell, J. E. Bennett, and R. Dolin (ed.), Principles and practice of infectious disease, 6th ed. Elsevier, Philadelphia, Pa.
    146.
    Suh, I. W., C. S. Park, M. S. Lee, J. H. Lee, M. S. Chang, J. H. Woo, I. C. Lee, and J. S. Ryu.2000. Hepatic and small bowel mucormycosis after chemotherapy in a patient with acute lymphocytic leukemia. J. Korean Med. Sci.15:351-354.
    147.
    Sun, Q. N., A. W. Fothergill, D. I. McCarthy, M. G. Rinaldi, and J. R. Graybill.2002. In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes. Antimicrob. Agents Chemother.46:1581-1582.
    148.
    Sun, Q. N., L. K. Najvar, R. Bocanegra, D. Loebenberg, and J. R. Graybill.2002. In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse model. Antimicrob. Agents Chemother.46:2310-2312.
    149.
    Talmi, Y. P., A. Goldschmied-Reouven, M. Bakon, I. Barshack, M. Wolf, Z. Horowitz, M. Berkowicz, N. Keller, and J. Kronenberg.2002. Rhino-orbital and rhino-orbito-cerebral mucormycosis. Otolaryngol. Head Neck Surg.127:22-31.
    150.
    Tedder, M., J. A. Spratt, M. P. Anstadt, S. S. Hegde, S. D. Tedder, and J. E. Lowe.1994. Pulmonary mucormycosis: results of medical and surgical therapy. Ann. Thorac. Surg.57:1044-1050.
    151.
    Teggi, A., A. Fedele, R. Bagnato, F. Traditi, C. M. Lanzalone, and F. De Rosa.1989. [A case of disseminated mucormycosis]. Recenti Prog. Med.80:308-313.
    152.
    ter Borg, F., E. J. Kuijper, and H. van der Lelie.1990. Fatal mucormycosis presenting as an appendiceal mass with metastatic spread to the liver during chemotherapy-induced granulocytopenia. Scand. J. Infect. Dis.22:499-501.
    153.
    Thajeb, P., T. Thajeb, and D. Dai.2004. Fatal strokes in patients with rhino-orbito-cerebral mucormycosis and associated vasculopathy. Scand. J. Infect. Dis.36:643-648.
    154.
    Tietz, H. J., D. Brehmer, W. Jänisch, and H. Martin.1998. Incidence of endomycoses in the autopsy material of the Berlin Charité Hospital. Mycoses41(Suppl. 2):81-85.
    155.
    Tobon, A. M., M. Arango, D. Fernandez, and A. Restrepo.2003. Mucormycosis (zygomycosis) in a heart-kidney transplant recipient: recovery after posaconazole therapy. Clin. Infect. Dis.36:1488-1491.
    156.
    Tuder, R. M.1985. Myocardial infarct in disseminated mucormycosis: case report with special emphasis on the pathogenic mechanisms. Mycopathologia89:81-88.
    157.
    Vadeboncoeur, C., J. M. Walton, J. Raisen, P. Soucy, H. Lau, and S. Rubin.1994. Gastrointestinal mucormycosis causing an acute abdomen in the immunocompromised pediatric patient-three cases. J. Pediatr. Surg.29:1248-1249.
    158.
    Van Cutsem, J., and J. R. Boelaert.1989. Effects of deferoxamine, feroxamine and iron on experimental mucormycosis (zygomycosis). Kidney Int.36:1061-1068.
    159.
    Van Cutsem, J., F. Van Gerven, J. Fransen, and P. A. Janssen.1989. Treatment of experimental zygomycosis in guinea pigs with azoles and with amphotericin B. Chemotherapy35:267-272.
    160.
    Veis, J. H., R. Contiguglia, M. Klein, J. Mishell, A. C. Alfrey, and J. I. Shapiro.1987. Mucormycosis in deferoxamine-treated patients on dialysis [letter]. Ann. Intern. Med.107:258.
    161.
    Ventura, G. J., H. M. Kantarjian, E. Anaissie, R. L. Hopfer, and V. Fainstein.1986. Pneumonia with Cunninghamella species in patients with hematologic malignancies. A case report and review of the literature. Cancer58:1534-1536.
    162.
    Vesa, J., O. Bielsa, O. Arango, C. Lladó, and A. Gelabert.1992. Massive renal infarction due to mucormycosis in an AIDS patient. Infection20:234-236.
    163.
    Vigouroux, S., O. Morin, P. Moreau, F. Mechinaud, N. Morineau, B. Mahe, P. Chevallier, T. Guillaume, V. Dubruille, J. L. Harousseau, and N. Milpied.2005. Zygomycosis after prolonged use of voriconazole in immunocompromised patients with hematologic disease: attention required. Clin. Infect. Dis.40:e35-37.
    164.
    Virmani, R., D. H. Connor, and H. A. McAllister.1982. Cardiac mucormycosis. A report of five patients and review of 14 previously reported cases. Am. J. Clin. Pathol.78:42-47.
    165.
    Voitl, P., C. Scheibenpflug, T. Weber, O. Janata, and A. M. Rokitansky.2002. Combined antifungal treatment of visceral mucormycosis with caspofungin and liposomal amphotericin B. Eur. J. Clin. Microbiol. Infect. Dis.21:632-634.
    166.
    Waldorf, A. R.1989. Pulmonary defense mechanisms against opportunistic fungal pathogens. Immunol. Ser.47:243-271.
    167.
    Waldorf, A. R., and R. D. Diamond.1984. Cerebral mucormycosis in diabetic mice after intrasinus challenge. Infect. Immun.44:194-195.
    168.
    Waldorf, A. R., C. Halde, and N. A. Vedros.1982. Murine model of pulmonary mucormycosis in cortisone-treated mice. Sabouraudia20:217-224.
    169.
    Waldorf, A. R., N. Ruderman, and R. D. Diamond.1984. Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus. J. Clin. Investig.74:150-160.
    170.
    Walsh, T. J., J. W. Hiemenz, N. L. Seibel, J. R. Perfect, G. Horwith, L. Lee, J. L. Silber, M. J. DiNubile, A. Reboli, E. Bow, J. Lister, and E. J. Anaissie.1998. Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases. Clin. Infect. Dis.26:1383-1396.
    171.
    Watts, W. J.1983. Bronchopleural fistula followed by massive fatal hemoptysis in a patient with pulmonary mucormycosis. A case report. Arch. Intern. Med.143:1029-1030.
    172.
    Welk, B., A. A. House, E. Ralph, E. Tweedy, and P. P. Luke.2004. Successful treatment of primary bilateral renal mucormycosis with bilateral nephrectomy. Urology64:590.
    173.
    Weng, D. E., W. H. Wilson, R. Little, and T. J. Walsh.1998. Successful medical management of isolated renal zygomycosis: case report and review. Clin. Infect. Dis.26:601-605.
    174.
    White, C. B., P. J. Barcia, and J. W. Bass.1986. Neonatal zygomycotic necrotizing cellulitis. Pediatrics78:100-102.
    175.
    Wolf, O., Z. Gil, L. Leider-Trejo, A. Khafif, P. Biderman, and D. M. Fliss.2004. Tracheal mucormycosis presented as an intraluminal soft tissue mass. Head Neck26:541-543.
    176.
    Woods, K. F., and B. J. Hanna.1986. Brain stem mucormycosis in a narcotic addict with eventual recovery. Am. J. Med.80:126-128.
    177.
    Woodward, A., C. McTigue, G. Hogg, A. Watkins, and H. Tan.1992. Mucormycosis of the neonatal gut: a “new” disease or a variant of necrotizing enterocolitis? J. Pediatr. Surg.27:737-740.
    178.
    Yamazaki, T., H. Kume, S. Murase, E. Yamashita, and M. Arisawa.1999. Epidemiology of visceral mycoses: analysis of data in annual of the pathological autopsy cases in Japan. J. Clin. Microbiol.37:1732-1738.
    179.
    Yanagisawa, E., S. Friedman, R. S. Kundargi, and H. W. Smith.1977. Rhinocerebral phycomycosis. Laryngoscope87:1319-1335.

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    Clinical Microbiology Reviews
    Volume 18Number 3July 2005
    Pages: 556 - 569

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    Brad Spellberg [email protected]
    Department of Medicine, Los Angeles Biomedical Institute at Harbor-UCLA Medical Center, Torrance, California
    David Geffen School of Medicine at UCLA, Los Angeles, California
    John Edwards Jr.
    Department of Medicine, Los Angeles Biomedical Institute at Harbor-UCLA Medical Center, Torrance, California
    David Geffen School of Medicine at UCLA, Los Angeles, California
    Ashraf Ibrahim
    Department of Medicine, Los Angeles Biomedical Institute at Harbor-UCLA Medical Center, Torrance, California
    David Geffen School of Medicine at UCLA, Los Angeles, California

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  • Clinical Microbiology ReviewsArticle
    Clinical Microbiology Informatics

    SUMMARY

    The clinical microbiology laboratory has responsibilities ranging from characterizing the causative agent in a patient's infection to helping detect global disease outbreaks. All of these processes are increasingly becoming partnered more intimately with informatics. Effective application of informatics tools can increase the accuracy, timeliness, and completeness of microbiology testing while decreasing the laboratory workload, which can lead to optimized laboratory workflow and decreased costs. Informatics is poised to be increasingly relevant in clinical microbiology, with the advent of total laboratory automation, complex instrument interfaces, electronic health records, clinical decision support tools, and the clinical implementation of microbial genome sequencing. This review discusses the diverse informatics aspects that are relevant to the clinical microbiology laboratory, including the following: the microbiology laboratory information system, decision support tools, expert systems, instrument interfaces, total laboratory automation, telemicrobiology, automated image analysis, nucleic acid sequence databases, electronic reporting of infectious agents to public health agencies, and disease outbreak surveillance. The breadth and utility of informatics tools used in clinical microbiology have made them indispensable to contemporary clinical and laboratory practice. Continued advances in technology and development of these informatics tools will further improve patient and public health care in the future.

    REFERENCES

    1.
    Campos JM. 2003. Clinical microbiology informatics—its time has come. Rev. Med. Microbiol. 14:105–108.
    2.
    El-Kareh R, Roy C, Williams DH, and Poon EG. 2012. Impact of automated alerts on follow-up of post-discharge microbiology results: a cluster randomized controlled trial. J. Gen. Intern. Med. 27:1243–1250.
    3.
    Scheid P, Lam DM, Thommes A, and Zoller L. 2007. Telemicrobiology: a novel telemedicine capability for mission support in the field of infectious medicine. Telemed. J. E Health 13:108–117.
    4.
    Shaw R, Coia JE, and Michie J. 1999. Use of bar code readers and programmable keypads to improve the speed and accuracy of manual data entry in the clinical microbiology laboratory: experience of two laboratories. J. Clin. Pathol. 52:54–60.
    5.
    Yu VL, Fagan LM, Wraith SM, Clancey WJ, Scott AC, Hannigan J, Blum RL, Buchanan BG, and Cohen SN. 1979. Antimicrobial selection by a computer. A blinded evaluation by infectious diseases experts. JAMA 242:1279–1282.
    6.
    Lau AF, Drake SK, Calhoun LB, Henderson CM, and Zelazny AM. 2013. Development of a clinically comprehensive database and a simple procedure for identification of molds from solid media by matrix-assisted laser desorption ionization–time of flight mass spectrometry. J. Clin. Microbiol. 51:828–834.
    7.
    Effler P, Ching-Lee M, Bogard A, Ieong MC, Nekomoto T, and Jernigan D. 1999. Statewide system of electronic notifiable disease reporting from clinical laboratories: comparing automated reporting with conventional methods. JAMA 282:1845–1850.
    8.
    Thomson RB Jr, Wilson ML, and Weinstein MP. 2010. The clinical microbiology laboratory director in the United States hospital setting. J. Clin. Microbiol. 48:3465–3469.
    9.
    Bergqvist F and Bengtsson S. 1975. The BACTLAB system—a data system for bacteriological routine. Comput. Programs Biomed. 4:144–157.
    10.
    Forsum U and Kronvall G. 2007. Clinical microbiology informatics—developments in Sweden. 1939. APMIS 115:415–421.
    11.
    Pantanowitz L, Tuthill JM, and Balis UGJ. 2012. Pathology informatics: theory and practice, p 162–164. ASCP, Chicago, IL.
    12.
    Snyder SR, Favoretto AM, Derzon JH, Christenson RH, Kahn SE, Shaw CS, Baetz RA, Mass D, Fantz CR, Raab SS, Tanasijevic MJ, and Liebow EB. 2012. Effectiveness of barcoding for reducing patient specimen and laboratory testing identification errors: a laboratory medicine best practices systematic review and meta-analysis. Clin. Biochem. 45:988.
    13.
    Pantanowitz L, Tuthill JM, and Balis UGJ. 2012. Pathology informatics: theory and practice, p 286–296. ASCP, Chicago, IL.
    14.
    Paxton A. 2012. Finally, microbiology labs getting a lift from IT. CAP Today 26:32–40.
    15.
    Ackerman VP, Pritchard RC, Groot Obbink DJ, Bradbury R, and Lee A. 1980. Reporting practices of microbiology laboratories. J. Clin. Pathol. 33:830–835.
    16.
    Willard KE, Connelly DP, and Johnson JR. 1996. Radical improvements in the display of clinical microbiology results: a Web-based clinical information system. Am. J. Med. 101:541–549.
    17.
    Brossette SE and Hymel PA Jr. 2008. Data mining and infection control. Clin. Lab. Med. 28:119–126.
    18.
    Aller RD and Friedman W. 1996. Rapid accurate entry of microbiology results. Arch. Pathol. Lab. Med. 120:57–61.
    19.
    Willard KE and Shanholtzer CJ. 1995. User interface reengineering. Innovative applications of bar coding in a clinical microbiology laboratory. Arch. Pathol. Lab. Med. 119:706–712.
    20.
    College of American Pathologists. 2014. Laboratory general checklist. College of American Pathologists, Northfield, IL.
    21.
    Evans RS, Pestotnik SL, Classen DC, Clemmer TP, Weaver LK, Orme JF Jr, Lloyd JF, and Burke JP. 1998. A computer-assisted management program for antibiotics and other antiinfective agents. N. Engl. J. Med. 338:232–238.
    22.
    Schreckenberger PC and Binnicker MJ. 2011. Optimizing antimicrobial susceptibility test reporting. J. Clin. Microbiol. 49:S15–S19.
    23.
    Evans RS, Pestotnik SL, Classen DC, and Burke JP. 1993. Development of an automated antibiotic consultant. M.D. Comput. 10:17–22.
    24.
    Perez KK, Olsen RJ, Musick WL, Cernoch PL, Davis JR, Land GA, Peterson LE, and Musser JM. 2013. Integrating rapid pathogen identification and antimicrobial stewardship significantly decreases hospital costs. Arch. Pathol. Lab. Med. 137:1247–1254.
    25.
    Bruins MJ, Ruijs GJ, Wolfhagen MJ, Bloembergen P, and Aarts JE. 2011. Does electronic clinical microbiology results reporting influence medical decision making: a pre- and post-interview study of medical specialists. BMC Med. Inform. Decis. Mak. 11:19.
    26.
    Leuthner KD and Doern GV. 2013. Antimicrobial stewardship programs. J. Clin. Microbiol. 51:3916–3920.
    27.
    Pogue JM, Mynatt RP, Marchaim D, Zhao JJ, Barr VO, Moshos J, Sunkara B, Chopra T, Chidurala S, and Kaye KS. 2014. Automated alerts coupled with antimicrobial stewardship intervention lead to decreases in length of stay in patients with gram-negative bacteremia. Infect. Control Hosp. Epidemiol. 35:132–138.
    28.
    Hindler JF and Stelling J. 2007. Analysis and presentation of cumulative antibiograms: a new consensus guideline from the Clinical and Laboratory Standards Institute. Clin. Infect. Dis. 44:867–873.
    29.
    Peterson LR and Brossette SE. 2002. Hunting health care-associated infections from the clinical microbiology laboratory: passive, active, and virtual surveillance. J. Clin. Microbiol. 40:1–4.
    30.
    Trevino S. 2000. Antibiotic resistance monitoring: a laboratory perspective. Mil. Med. 165:40–42.
    31.
    CLSI. 2014. M29-A4. Analysis and presentation of cumulative antimicrobial susceptibility test data; approved guideline, 4th ed. Clinical and Laboratory Standards Institute, Wayne, PA.
    32.
    Shortliffe EH, Davis R, Axline SG, Buchanan BG, Green CC, and Cohen SN. 1975. Computer-based consultations in clinical therapeutics: explanation and rule acquisition capabilities of the MYCIN system. Comput. Biomed. Res. 8:303–320.
    33.
    Wilson G, Badarudeen S, and Godwin A. 2010. Real-time validation and presentation of the cumulative antibiogram and implications of presenting a standard format using a novel in-house software: ABSOFT. Am. J. Infect. Control 38:e25–e30.
    34.
    Evans RS, Classen DC, Pestotnik SL, Lundsgaarde HP, and Burke JP. 1994. Improving empiric antibiotic selection using computer decision support. Arch. Intern. Med. 154:878–884.
    35.
    Trick WE, Zagorski BM, Tokars JI, Vernon MO, Welbel SF, Wisniewski MF, Richards C, and Weinstein RA. 2004. Computer algorithms to detect bloodstream infections. Emerg. Infect. Dis. 10:1612–1620.
    36.
    Polis MA. 2013. ACP Journal Club: a clinical decision-support system with interactive alerts improved CD4 cell count in HIV. Ann. Intern. Med. 158:JC11.
    37.
    Schurink CA, Lucas PJ, Hoepelman IM, and Bonten MJ. 2005. Computer-assisted decision support for the diagnosis and treatment of infectious diseases in intensive care units. Lancet Infect. Dis. 5:305–312.
    38.
    Winstanley T and Courvalin P. 2011. Expert systems in clinical microbiology. Clin. Microbiol. Rev. 24:515–556.
    39.
    El-Kareh R, Roy C, Brodsky G, Perencevich M, and Poon EG. 2011. Incidence and predictors of microbiology results returning postdischarge and requiring follow-up. J. Hosp. Med. 6:291–296.
    40.
    Wilson JW, Marshall WF, and Estes LL. 2011. Detecting delayed microbiology results after hospital discharge: improving patient safety through an automated medical informatics tool. Mayo Clin. Proc. 86:1181–1185.
    41.
    Leis JA, Rebick GW, Daneman N, Gold WL, Poutanen SM, Lo P, Larocque M, Shojania KG, and McGeer A. 2014. Reducing antimicrobial therapy for asymptomatic bacteriuria among noncatheterized inpatients: a proof-of-concept study. Clin. Infect. Dis. 58:980–983.
    42.
    College of American Pathologists. 2012. Microbiology checklist. College of American Pathologists, Northfield, IL.
    43.
    Ebbert MT, Mallory MA, Wilson AR, Dooley SK, and Hillyard DR. 2013. Application of a new informatics tool for contamination screening in the HIV sequencing laboratory. J. Clin. Virol. 57:249–253.
    44.
    Paterson DL and Bonomo RA. 2005. Extended-spectrum beta-lactamases: a clinical update. Clin. Microbiol. Rev. 18:657–686.
    45.
    Sanders CC, Peyret M, Moland ES, Shubert C, Thomson KS, Boeufgras JM, and Sanders WE Jr. 2000. Ability of the VITEK 2 advanced expert system to identify beta-lactam phenotypes in isolates of Enterobacteriaceae and Pseudomonas aeruginosa. J. Clin. Microbiol. 38:570–574.
    46.
    Becton, Dickinson, and Company. 2008. LIS vendor interface document. Becton, Dickinson, and Company, Sparks, MD.
    47.
    Astion ML, Shojania KG, Hamill TR, Kim S, and Ng VL. 2003. Classifying laboratory incident reports to identify problems that jeopardize patient safety. Am. J. Clin. Pathol. 120:18–26.
    48.
    Morris AJ, Haremza E, and Walker DA. 2011. The frequency and potential clinical impact of non-analytical errors in the RCPA Microbiology QAP 1987–2008. Pathology 43:346–349.
    49.
    Blank GE and Virji MA. 2011. Development and implementation of an electronic interface for complex clinical laboratory instruments without a vendor-provided data transfer interface. J. Pathol. Inform. 2:14.
    50.
    French D and Terrazas E. 2013. The successful implementation of a licensed data management interface between a Sunquest(R) laboratory information system and an AB SCIEX mass spectrometer. J. Pathol. Inform. 4:1.
    51.
    Huang SS, Yokoe DS, Stelling J, Placzek H, Kulldorff M, Kleinman K, O'Brien TF, Calderwood MS, Vostok J, Dunn J, and Platt R. 2010. Automated detection of infectious disease outbreaks in hospitals: a retrospective cohort study. PLoS Med. 7:e1000238.
    52.
    bioMérieux. 2006. Bidirectional computer interface specification for VITEK systems. bioMérieux, Inc., Durham, NC.
    53.
    Siemens. 2010. Siemens LabPro interface implementation guide 9020-7424, rev A. Siemens, West Sacramento, CA.
    54.
    Espy MJ, Uhl JR, Sloan LM, Buckwalter SP, Jones MF, Vetter EA, Yao JD, Wengenack NL, Rosenblatt JE, Cockerill FR 3rd, and Smith TF. 2006. Real-time PCR in clinical microbiology: applications for routine laboratory testing. Clin. Microbiol. Rev. 19:165–256.
    55.
    Rhoads DD, Cox SB, Rees EJ, Sun Y, and Wolcott RD. 2012. Clinical identification of bacteria in human chronic wound infections: culturing vs. 16S ribosomal DNA sequencing. BMC Infect. Dis. 12:321.
    56.
    Salipante SJ, Sengupta DJ, Rosenthal C, Costa G, Spangler J, Sims EH, Jacobs MA, Miller SI, Hoogestraat DR, Cookson BT, McCoy C, Matsen FA, Shendure J, Lee CC, Harkins TT, and Hoffman NG. 2013. Rapid 16S rRNA next-generation sequencing of polymicrobial clinical samples for diagnosis of complex bacterial infections. PLoS One 8:e65226.
    57.
    Gen-Probe. 2011. Tigris DTS system LIS1-A & LIS2-A2 interface guide for LIS programmers, 902621, rev C. Gen-Probe, San Diego, CA.
    58.
    Williams RE and Trotman RE. 1969. Automation in diagnostic bacteriology. J. Clin. Pathol. Suppl. Coll. Pathol. 3:8–13.
    59.
    Bourbeau PP and Ledeboer NA. 2013. Automation in clinical microbiology. J. Clin. Microbiol. 51:1658–1665.
    60.
    Novak SM and Marlowe EM. 2013. Automation in the clinical microbiology laboratory. Clin. Lab. Med. 33:567–588.
    61.
    Greub G and Prod'hom G. 2011. Automation in clinical bacteriology: what system to choose? Clin. Microbiol. Infect. 17:655–660.
    62.
    Mutters NT, Hodiamont CJ, de Jong MD, Overmeijer HP, van den Boogaard M, and Visser CE. 2014. Performance of Kiestra total laboratory automation combined with MS in clinical microbiology practice. Ann. Lab. Med. 34:111–117.
    63.
    Paxton A. 2014. Labs weighing pros, cons of micro TLA. CAP Today 28:1, 26–29.
    64.
    Matthews S and Deutekom J. 2011. The future of diagnostic bacteriology. Clin. Microbiol. Infect. 17:651–654.
    65.
    Froment P, Marchandin H, Vande Perre P, and Lamy B. 2014. Automated versus manual sample inoculations in routine clinical microbiology: a performance evaluation of the fully automated InoqulA instrument. J. Clin. Microbiol. 52:796–802.
    66.
    Burnham CA, Dunne WM Jr, Greub G, Novak SM, and Patel R. 2013. Automation in the clinical microbiology laboratory. Clin. Chem. 59:1696–1702.
    67.
    Pantanowitz L, Sinard JH, Henricks WH, Fatheree LA, Carter AB, Contis L, Beckwith BA, Evans AJ, Otis CN, Lal A, and Parwani AV. 2013. Validating whole slide imaging for diagnostic purposes in pathology: guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch. Pathol. Lab. Med. 137:1710–1722.
    68.
    Pantanowitz L, Wiley CA, Demetris A, Lesniak A, Ahmed I, Cable W, Contis L, and Parwani AV. 2012. Experience with multimodality telepathology at the University of Pittsburgh Medical Center. J. Pathol. Inform. 3:45.
    69.
    Lee LH, Mansoor A, Wood B, Nelson H, Higa D, and Naugler C. 2013. Performance of CellaVision DM96 in leukocyte classification. J. Pathol. Inform. 4:14.
    70.
    Levi AW, Chhieng DC, Schofield K, Kowalski D, and Harigopal M. 2012. Implementation of FocalPoint GS location-guided imaging system: experience in a clinical setting. Cancer Cytopathol. 120:126–133.
    71.
    Suhanic W, Crandall I, and Pennefather P. 2009. An informatics model for guiding assembly of telemicrobiology workstations for malaria collaborative diagnostics using commodity products and open-source software. Malar. J. 8:164.
    72.
    McLaughlin WJ, Schifman RB, Ryan KJ, Manriquez GM, Bhattacharyya AK, Dunn BE, and Weinstein RS. 1998. Telemicrobiology: feasibility study. Telemed. J. 4:11–17.
    73.
    Campbell WS, Lele SM, West WW, Lazenby AJ, Smith LM, and Hinrichs SH. 2012. Concordance between whole-slide imaging and light microscopy for routine surgical pathology. Hum. Pathol. 43:1739–1744.
    74.
    Sadaphal P, Rao J, Comstock GW, and Beg MF. 2008. Image processing techniques for identifying Mycobacterium tuberculosis in Ziehl-Neelsen stains. Int. J. Tuberc. Lung Dis. 12:579–582.
    75.
    Pandolfi D and Pons MN. 2004. Gram-staining characterisation of activated sludge filamentous bacteria by automated colour analysis. Biotechnol. Lett. 26:1841–1846.
    76.
    Ingels N and Daughters G. 1968. New design for an automated bacterial colony counter. Rev. Sci. Instrum. 39:115–120.
    77.
    Marotz J, Lubbert C, and Eisenbeiss W. 2001. Effective object recognition for automated counting of colonies in Petri dishes (automated colony counting). Comput. Methods Programs Biomed. 66:183–198.
    78.
    Brugger SD, Baumberger C, Jost M, Jenni W, Brugger U, and Muhlemann K. 2012. Automated counting of bacterial colony forming units on agar plates. PLoS One 7:e33695.
    79.
    Geissmann Q. 2013. OpenCFU, a new free and open-source software to count cell colonies and other circular objects. PLoS One 8:e54072.
    80.
    Wilson BK and Vigil GD. 2013. Automated bacterial identification by angle resolved dark-field imaging. Biomed. Optics Express 4:1692–1701.
    81.
    Lewis JJ, Chihota VN, van der Meulen M, Fourie PB, Fielding KL, Grant AD, Dorman SE, and Churchyard GJ. 2012. “Proof-of-concept” evaluation of an automated sputum smear microscopy system for tuberculosis diagnosis. PLoS One 7:e50173.
    82.
    Patel B and Douglas TS. 2012. Creating a virtual slide map from sputum smear images for region-of-interest localisation in automated microscopy. Comput. Methods Programs Biomed. 108:38–52.
    83.
    Khutlang R, Krishnan S, Dendere R, Whitelaw A, Veropoulos K, Learmonth G, and Douglas TS. 2010. Classification of Mycobacterium tuberculosis in images of ZN-stained sputum smears. IEEE Trans. Inf. Technol. Biomed. 14:949–957.
    84.
    Di Ruberto C, Dempster A, Khan S, and Jarra B. 2002. Analysis of infected blood cell images using morphological operators. Image Vision Comput. 20:133–146.
    85.
    Kaewkamnerd S, Uthaipibull C, Intarapanich A, Pannarut M, Chaotheing S, and Tongsima S. 2012. An automatic device for detection and classification of malaria parasite species in thick blood film. BMC Bioinform. 13(Suppl 17):S18.
    86.
    Le MT, Bretschneider TR, Kuss C, and Preiser PR. 2008. A novel semi-automatic image processing approach to determine Plasmodium falciparum parasitemia in Giemsa-stained thin blood smears. BMC Cell Biol. 9:15.
    87.
    Murray CK, Mody RM, Dooley DP, Hospenthal DR, Horvath LL, Moran KA, and Muntz RW. 2006. The remote diagnosis of malaria using telemedicine or e-mailed images. Mil. Med. 171:1167–1171.
    88.
    Prasad K, Winter J, Bhat UM, Acharya RV, and Prabhu GK. 2012. Image analysis approach for development of a decision support system for detection of malaria parasites in thin blood smear images. J. Digit. Imaging 25:542–549.
    89.
    Purwar Y, Shah SL, Clarke G, Almugairi A, and Muehlenbachs A. 2011. Automated and unsupervised detection of malarial parasites in microscopic images. Malar. J. 10:364.
    90.
    Ross NE, Pritchard CJ, Rubin DM, and Duse AG. 2006. Automated image processing method for the diagnosis and classification of malaria on thin blood smears. Med. Biol. Eng. Comput. 44:427–436.
    91.
    Comina G, Mendoza D, Velazco A, Coronel J, Sheen P, Gilman RH, Moore DA, and Zimic M. 2011. Development of an automated MODS plate reader to detect early growth of Mycobacterium tuberculosis. J. Microsc. 242:325–330.
    92.
    Jeong J, Kim SR, Lee SH, Lim JH, Choi JI, Park JS, Chang CL, Choi JY, Richman DD, and Smith DM. 2011. The use of high performance liquid chromatography to speciate and characterize the epidemiology of mycobacteria. Lab. Med. 42:612–617.
    93.
    Butler WR and Guthertz LS. 2001. Mycolic acid analysis by high-performance liquid chromatography for identification of Mycobacterium species. Clin. Microbiol. Rev. 14:704–726.
    94.
    Kellogg JA, Bankert DA, Withers GS, Sweimler W, Kiehn TE, and Pfyffer GE. 2001. Application of the Sherlock Mycobacteria identification system using high-performance liquid chromatography in a clinical laboratory. J. Clin. Microbiol. 39:964–970.
    95.
    Bhadra B, Roy P, and Chakraborty R. 2005. Serratia ureilytica sp. nov., a novel urea-utilizing species. Int. J. Syst. Evol. Microbiol. 55:2155–2158.
    96.
    Rychert J, Burnham CA, Bythrow M, Garner OB, Ginocchio CC, Jennemann R, Lewinski MA, Manji R, Mochon AB, Procop GW, Richter SS, Sercia L, Westblade LF, Ferraro MJ, and Branda JA. 2013. Multicenter evaluation of the Vitek MS matrix-assisted laser desorption ionization–time of flight mass spectrometry system for identification of Gram-positive aerobic bacteria. J. Clin. Microbiol. 51:2225–2231.
    97.
    Clark AE, Kaleta EJ, Arora A, and Wolk DM. 2013. Matrix-assisted laser desorption ionization–time of flight mass spectrometry: a fundamental shift in the routine practice of clinical microbiology. Clin. Microbiol. Rev. 26:547–603.
    98.
    Patel R. 2013. Matrix-assisted laser desorption ionization–time of flight mass spectrometry in clinical microbiology. Clin. Infect. Dis. 57:564–572.
    99.
    Bohme K, Fernandez-No IC, Barros-Velazquez J, Gallardo JM, Canas B, and Calo-Mata P. 2012. SpectraBank: an open access tool for rapid microbial identification by MALDI-TOF MS fingerprinting. Electrophoresis 33:2138–2142.
    100.
    CLSI. 2008. MM18-A. Interpretive criteria for identification of bacteria and fungi by DNA target sequencing; approved guideline. Clinical and Laboratory Standards Institute, Wayne, PA.
    101.
    Long SW, Williams D, Valson C, Cantu CC, Cernoch P, Musser JM, and Olsen RJ. 2013. A genomic day in the life of a clinical microbiology laboratory. J. Clin. Microbiol. 51:1272–1277.
    102.
    O'Farrell B, Haase JK, Velayudhan V, Murphy RA, and Achtman M. 2012. Transforming microbial genotyping: a robotic pipeline for genotyping bacterial strains. PLoS One 7:e48022.
    103.
    Fricke WF and Rasko DA. 2014. Bacterial genome sequencing in the clinic: bioinformatic challenges and solutions. Nat. Rev. Genet. 15:49–55.
    104.
    Hasman H, Saputra D, Sicheritz-Ponten T, Lund O, Svendsen CA, Frimodt-Moller N, and Aarestrup FM. 2014. Rapid whole-genome sequencing for detection and characterization of microorganisms directly from clinical samples. J. Clin. Microbiol. 52:139–146.
    105.
    Reuter S, Ellington MJ, Cartwright EJ, Koser CU, Torok ME, Gouliouris T, Harris SR, Brown NM, Holden MT, Quail M, Parkhill J, Smith GP, Bentley SD, and Peacock SJ. 2013. Rapid bacterial whole-genome sequencing to enhance diagnostic and public health microbiology. JAMA Intern. Med. 173:1397–1404.
    106.
    Dunne WM Jr, Westblade LF, and Ford B. 2012. Next-generation and whole-genome sequencing in the diagnostic clinical microbiology laboratory. Eur. J. Clin. Microbiol. Infect. Dis. 31:1719–1726.
    107.
    Janda JM and Abbott SL. 2007. 16S rRNA gene sequencing for bacterial identification in the diagnostic laboratory: pluses, perils, and pitfalls. J. Clin. Microbiol. 45:2761–2764.
    108.
    Boudewijns M, Bakkers JM, Sturm PD, and Melchers WJ. 2006. 16S rRNA gene sequencing and the routine clinical microbiology laboratory: a perfect marriage? J. Clin. Microbiol. 44:3469–3470.
    109.
    Conville PS, Murray PR, and Zelazny AM. 2010. Evaluation of the integrated database network system (IDNS) SmartGene software for analysis of 16S rRNA gene sequences for identification of Nocardia species. J. Clin. Microbiol. 48:2995–2998.
    110.
    Clarridge JE 3rd. 2004. Impact of 16S rRNA gene sequence analysis for identification of bacteria on clinical microbiology and infectious diseases. Clin. Microbiol. Rev. 17:840–862.
    111.
    Tortoli E. 2010. Standard operating procedure for optimal identification of mycobacteria using 16S rRNA gene sequences. Stand. Genomic Sci. 3:145–152.
    112.
    Hall BG. 2013. Building phylogenetic trees from molecular data with MEGA. Mol. Biol. Evol. 30:1229–1235.
    113.
    Woo PC, Teng JL, Yeung JM, Tse H, Lau SK, and Yuen KY. 2011. Automated identification of medically important bacteria by 16S rRNA gene sequencing using a novel comprehensive database, 16SpathDB. J. Clin. Microbiol. 49:1799–1809.
    114.
    Mohamed AM, Kuyper DJ, Iwen PC, Ali HH, Bastola DR, and Hinrichs SH. 2005. Computational approach involving use of the internal transcribed spacer 1 region for identification of Mycobacterium species. J. Clin. Microbiol. 43:3811–3817.
    115.
    Hartman AL, Riddle S, McPhillips T, Ludascher B, and Eisen JA. 2010. Introducing W.A.T.E.R.S.: a workflow for the alignment, taxonomy, and ecology of ribosomal sequences. BMC Bioinform. 11:317.
    116.
    Woo PC, Lau SK, Teng JL, Tse H, and Yuen KY. 2008. Then and now: use of 16S rDNA gene sequencing for bacterial identification and discovery of novel bacteria in clinical microbiology laboratories. Clin. Microbiol. Infect. 14:908–934.
    117.
    Didelot X, Bowden R, Wilson DJ, Peto TE, and Crook DW. 2012. Transforming clinical microbiology with bacterial genome sequencing. Nat. Rev. Genet. 13:601–612.
    118.
    Koser CU, Ellington MJ, Cartwright EJ, Gillespie SH, Brown NM, Farrington M, Holden MT, Dougan G, Bentley SD, Parkhill J, and Peacock SJ. 2012. Routine use of microbial whole genome sequencing in diagnostic and public health microbiology. PLoS Pathog. 8:e1002824.
    119.
    Koser CU, Holden MT, Ellington MJ, Cartwright EJ, Brown NM, Ogilvy-Stuart AL, Hsu LY, Chewapreecha C, Croucher NJ, Harris SR, Sanders M, Enright MC, Dougan G, Bentley SD, Parkhill J, Fraser LJ, Betley JR, Schulz-Trieglaff OB, Smith GP, and Peacock SJ. 2012. Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. N. Engl. J. Med. 366:2267–2275.
    120.
    Loman NJ, Constantinidou C, Christner M, Rohde H, Chan JZ, Quick J, Weir JC, Quince C, Smith GP, Betley JR, Aepfelbacher M, and Pallen MJ. 2013. A culture-independent sequence-based metagenomics approach to the investigation of an outbreak of Shiga-toxigenic Escherichia coli O104:H4. JAMA 309:1502–1510.
    121.
    Fournier PE, Drancourt M, Colson P, Rolain JM, Scola BL, and Raoult D. 2013. Modern clinical microbiology: new challenges and solutions. Nat. Rev. Microbiol. 11:574–585.
    122.
    Bertelli C and Greub G. 2013. Rapid bacterial genome sequencing: methods and applications in clinical microbiology. Clin. Microbiol. Infect. 19:803–813.
    123.
    Ehrlich GD, Hu FZ, Shen K, Stoodley P, and Post JC. 2005. Bacterial plurality as a general mechanism driving persistence in chronic infections. Clin. Orthop. Relat. Res. 2005:20–24.
    124.
    Shen K, Sayeed S, Antalis P, Gladitz J, Ahmed A, Dice B, Janto B, Dopico R, Keefe R, Hayes J, Johnson S, Yu S, Ehrlich N, Jocz J, Kropp L, Wong R, Wadowsky RM, Slifkin M, Preston RA, Erdos G, Post JC, Ehrlich GD, and Hu FZ. 2006. Extensive genomic plasticity in Pseudomonas aeruginosa revealed by identification and distribution studies of novel genes among clinical isolates. Infect. Immun. 74:5272–5283.
    125.
    Costello EK, Stagaman K, Dethlefsen L, Bohannan BJ, and Relman DA. 2012. The application of ecological theory toward an understanding of the human microbiome. Science 336:1255–1262.
    126.
    Dowd SE, Wolcott RD, Sun Y, McKeehan T, Smith E, and Rhoads D. 2008. Polymicrobial nature of chronic diabetic foot ulcer biofilm infections determined using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP). PLoS One 3:e3326.
    127.
    Jiao D, Ye Y, and Tang H. 2013. Probabilistic inference of biochemical reactions in microbial communities from metagenomic sequences. PLoS Comput. Biol. 9:e1002981.
    128.
    Gilmour MW, Graham M, Reimer A, and Van Domselaar G. 2013. Public health genomics and the new molecular epidemiology of bacterial pathogens. Public Health Genomics 16:25–30.
    129.
    Gardy JL, Johnston JC, Ho Sui SJ, Cook VJ, Shah L, Brodkin E, Rempel S, Moore R, Zhao Y, Holt R, Varhol R, Birol I, Lem M, Sharma MK, Elwood K, Jones SJ, Brinkman FS, Brunham RC, and Tang P. 2011. Whole-genome sequencing and social-network analysis of a tuberculosis outbreak. N. Engl. J. Med. 364:730–739.
    130.
    Underwood AP, Dallman T, Thomson NR, Williams M, Harker K, Perry N, Adak B, Willshaw G, Cheasty T, Green J, Dougan G, Parkhill J, and Wain J. 2013. Public health value of next-generation DNA sequencing of enterohemorrhagic Escherichia coli isolates from an outbreak. J. Clin. Microbiol. 51:232–237.
    131.
    Rhoads DD, Wolcott RD, Sun Y, and Dowd SE. 2012. Comparison of culture and molecular identification of bacteria in chronic wounds. Int. J. Mol. Sci. 13:2535–2550.
    132.
    Chumpitazi BP, Hollister EB, Oezguen N, Tsai CM, McMeans AR, Luna RA, Savidge TC, Versalovic J, and Shulman RJ. 2014. Gut microbiota influences low fermentable substrate diet efficacy in children with irritable bowel syndrome. Gut Microbes 5:165–175.
    133.
    Wilson MR, Naccache SN, Samayoa E, Biagtan M, Bashir H, Yu G, Salamat SM, Somasekar S, Federman S, Miller S, Sokolic R, Garabedian E, Candotti F, Buckley RH, Reed KD, Meyer TL, Seroogy CM, Galloway R, Henderson SL, Gern JE, DeRisi JL, and Chiu CY. 2014. Actionable diagnosis of neuroleptospirosis by next-generation sequencing. N. Engl. J. Med. 370:2408–2417.
    134.
    Schloss PD, Gevers D, and Westcott SL. 2011. Reducing the effects of PCR amplification and sequencing artifacts on 16S rRNA-based studies. PLoS One 6:e27310.
    135.
    Gaspar JM and Thomas WK. 2013. Assessing the consequences of denoising marker-based metagenomic data. PLoS One 8:e60458.
    136.
    Wright ES, Yilmaz LS, and Noguera DR. 2012. DECIPHER, a search-based approach to chimera identification for 16S rRNA sequences. Appl. Environ. Microbiol. 78:717–725.
    137.
    Hwang K, Oh J, Kim TK, Kim BK, Yu DS, Hou BK, Caetano-Anolles G, Hong SG, and Kim KM. 2013. CLUSTOM: a novel method for clustering 16S rRNA next generation sequences by overlap minimization. PLoS One 8:e62623.
    138.
    Zheng Z, Kramer S, and Schmidt B. 2012. DySC: software for greedy clustering of 16S rRNA reads. Bioinformatics 28:2182–2183.
    139.
    Kuczynski J, Lauber CL, Walters WA, Parfrey LW, Clemente JC, Gevers D, and Knight R. 2012. Experimental and analytical tools for studying the human microbiome. Nat. Rev. Genet. 13:47–58.
    140.
    Lee JH, Yi H, Jeon YS, Won S, and Chun J. 2012. TBC: a clustering algorithm based on prokaryotic taxonomy. J. Microbiol. 50:181–185.
    141.
    Harris SR, Torok ME, Cartwright EJ, Quail MA, Peacock SJ, and Parkhill J. 2013. Read and assembly metrics inconsequential for clinical utility of whole-genome sequencing in mapping outbreaks. Nat. Biotechnol. 31:592–594.
    142.
    Duncavage EJ, Abel HJ, Szankasi P, Kelley TW, and Pfeifer JD. 2012. Targeted next generation sequencing of clinically significant gene mutations and translocations in leukemia. Mod. Pathol. 25:795–804.
    143.
    Schmidt KK. 28 May 2013, posting date. As outbreak continues, confusion reigns over virus patents. ScienceMag.org. http://news.sciencemag.org/people-events/2013/05/outbreak-continues-confusion-reigns-over-virus-patents.
    144.
    Kesselheim AS, Cook-Deegan RM, Winickoff DE, and Mello MM. 2013. Gene patenting—the Supreme Court finally speaks. N. Engl. J. Med. 369:869–875.
    145.
    Schloissnig S, Arumugam M, Sunagawa S, Mitreva M, Tap J, Zhu A, Waller A, Mende DR, Kultima JR, Martin J, Kota K, Sunyaev SR, Weinstock GM, and Bork P. 2013. Genomic variation landscape of the human gut microbiome. Nature 493:45–50.
    146.
    Sweeney L, Abu A, and Winn J. 24 April 2013. Identifying participants in the personal genome project by name. White paper 1021-1. dataprivacylab.org.
    147.
    Benschop K, Thomas X, Serpenti C, Molenkamp R, and Wolthers K. 2008. High prevalence of human parechovirus (HPeV) genotypes in the Amsterdam region and identification of specific HPeV variants by direct genotyping of stool samples. J. Clin. Microbiol. 46:3965–3970.
    148.
    Rodriquez-R LM and Konstantinidis KT. 2014. Bypassing cultivation to identify bacterial species. Microbe 9:111–118. http://www.microbemagazine.org/index.php?option=com_content&view=category&layout=blog&id=1318&Itemid=1591.
    149.
    Gevers D, Cohan FM, Lawrence JG, Spratt BG, Coenye T, Feil EJ, Stackebrandt E, Van de Peer Y, Vandamme P, Thompson FL, and Swings J. 2005. Opinion: re-evaluating prokaryotic species. Nat. Rev. Microbiol. 3:733–739.
    150.
    Vayssier-Taussat M, Albina E, Citti C, Cosson JF, Jacques MA, Lebrun MH, Le Loir Y, Ogliastro M, Petit MA, Roumagnac P, and Candresse T. 2014. Shifting the paradigm from pathogens to pathobiome: new concepts in the light of meta-omics. Front. Cell. Infect. Microbiol. 4:29.
    151.
    Fux CA, Shirtliff M, Stoodley P, and Costerton JW. 2005. Can laboratory reference strains mirror “real-world” pathogenesis? Trends Microbiol. 13:58–63.
    152.
    Krebes J, Morgan RD, Bunk B, Sproer C, Luong K, Parusel R, Anton BP, Konig C, Josenhans C, Overmann J, Roberts RJ, Korlach J, and Suerbaum S. 2014. The complex methylome of the human gastric pathogen Helicobacter pylori. Nucleic Acids Res. 42:2415–2432.
    153.
    Murray IA, Clark TA, Morgan RD, Boitano M, Anton BP, Luong K, Fomenkov A, Turner SW, Korlach J, and Roberts RJ. 2012. The methylomes of six bacteria. Nucleic Acids Res. 40:11450–11462.
    154.
    Lee CH, Belanger JE, Kassam Z, Smieja M, Higgins D, Broukhanski G, and Kim PT. 2014. The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema. Eur. J. Clin. Microbiol. Infect. Dis. 33:1425–1428.
    155.
    Cammarota G, Ianiro G, and Gasbarrini A. 2014. Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review. J. Clin. Gastroenterol. 48:693–702.
    156.
    van der Gast CJ, Cuthbertson L, Rogers GB, Pope C, Marsh RL, Redding GJ, Bruce KD, Chang AB, and Hoffman LR. 5 March 2014. Three clinically distinct chronic pediatric airway infections share a common core microbiota. Ann. Am. Thorac. Soc.
    157.
    Taniuchi M, Sobuz SU, Begum S, Platts-Mills JA, Liu J, Yang Z, Wang XQ, Petri WA Jr, Haque R, and Houpt ER. 2013. Etiology of diarrhea in Bangladeshi infants in the first year of life analyzed using molecular methods. J. Infect. Dis. 208:1794–1802.
    158.
    Kho AN, Doebbeling BN, Cashy JP, Rosenman MB, Dexter PR, Shepherd DC, Lemmon L, Teal E, Khokar S, and Overhage JM. 2013. A regional informatics platform for coordinated antibiotic-resistant infection tracking, alerting, and prevention. Clin. Infect. Dis. 57:254–262.
    159.
    Panackal AA, M'Ikanatha NM, Tsui FC, McMahon J, Wagner MM, Dixon BW, Zubieta J, Phelan M, Mirza S, Morgan J, Jernigan D, Pasculle AW, Rankin JT Jr, Hajjeh RA, and Harrison LH. 2002. Automatic electronic laboratory-based reporting of notifiable infectious diseases at a large health system. Emerg. Infect. Dis. 8:685–691.
    160.
    Wurtz R and Cameron BJ. 2005. Electronic laboratory reporting for the infectious diseases physician and clinical microbiologist. Clin. Infect. Dis. 40:1638–1643.
    161.
    CDC. 10 December 2013, posting date. National notifiable diseases surveillance system (NNDSS). CDC, Atlanta, GA. http://wwwn.cdc.gov/nndss/script/nedss.aspx.
    162.
    The International Health Terminology Standards Development Organisation and The Regenstrief Institute. 2013. Cooperation agreement 4846-5531-6754v6. http://loinc.org/collaboration/ihtsdo/agreement.pdf.
    163.
    National Electronic Disease Surveillance System Working Group. 2001. National Electronic Disease Surveillance System (NEDSS): a standards-based approach to connect public health and clinical medicine. J. Public Health Manag. Pract. 7:43–50.
    164.
    O'Brien TF and Stelling J. 2011. Integrated multilevel surveillance of the world's infecting microbes and their resistance to antimicrobial agents. Clin. Microbiol. Rev. 24:281–295.
    165.
    Pinner RW, Rebmann CA, Schuchat A, and Hughes JM. 2003. Disease surveillance and the academic, clinical, and public health communities. Emerg. Infect. Dis. 9:781–787.
    166.
    Stelling J, Yih WK, Galas M, Kulldorff M, Pichel M, Terragno R, Tuduri E, Espetxe S, Binsztein N, O'Brien TF, and Platt R. 2010. Automated use of WHONET and SaTScan to detect outbreaks of Shigella spp. using antimicrobial resistance phenotypes. Epidemiol. Infect. 138:873–883.
    167.
    Sintchenko V and Gallego B. 2009. Laboratory-guided detection of disease outbreaks: three generations of surveillance systems. Arch. Pathol. Lab. Med. 133:916–925.
    168.
    Sahm DF, Marsilio MK, and Piazza G. 1999. Antimicrobial resistance in key bloodstream bacterial isolates: electronic surveillance with the Surveillance Network Database—USA. Clin. Infect. Dis. 29:259–263.
    169.
    Stelling JM and O'Brien TF. 1997. Surveillance of antimicrobial resistance: the WHONET program. Clin. Infect. Dis. 24(Suppl 1):S157–S168.
    170.
    O'Brien TF and Stelling JM. 1996. WHONET: removing obstacles to the full use of information about antimicrobial resistance. Diagn. Microbiol. Infect. Dis. 25:162–168.
    171.
    O'Brien TF and Stelling JM. 1995. WHONET: an information system for monitoring antimicrobial resistance. Emerg. Infect. Dis. 1:66.
    172.
    Cullen IM, Manecksha RP, McCullagh E, Ahmad S, O'Kelly F, Flynn RJ, McDermott T, Murphy P, Grainger R, Fennell JP, and Thornhill JA. 2012. The changing pattern of antimicrobial resistance within 42,033 Escherichia coli isolates from nosocomial, community and urology patient-specific urinary tract infections, Dublin, 1999–2009. BJU Int. 109:1198–1206.
    173.
    Polwichai P, Dejsirilert S, Panpetch S, Sawanpanyalert P, Aswapokee N, and Mootsikapun P. 2009. Antimicrobial resistance of Escherichia coli isolated from urine in Thailand from 2000 to 2005. J. Med. Assoc. Thai. 92(Suppl 4):S59–S67.
    174.
    Vinas MR, Tuduri E, Galar A, Yih K, Pichel M, Stelling J, Brengi SP, Della Gaspera A, van der Ploeg C, Bruno S, Roge A, Caffer MI, Kulldorff M, and Galas M. 2013. Laboratory-based prospective surveillance for community outbreaks of Shigella spp. in Argentina. PLoS Negl. Trop. Dis. 7:e2521.
    175.
    O'Brien TF and Stelling J. 2014. The world's microbiology laboratories can be a global microbial sensor network. Biomedica 34(Suppl 1):9–15.
    176.
    Sahm DF, Thornsberry C, and Karlowsky JA. 2003. The application of information technology to regional, national, and global surveillance of antimicrobial resistance. Curr. Pharm. Des. 9:969–974.
    177.
    Peterson LR, Hacek DM, Rolland D, and Brossette SE. 2003. Detection of a community infection outbreak with virtual surveillance. Lancet 362:1587–1588.
    178.
    Bouam S, Girou E, Brun-Buisson C, Karadimas H, and Lepage E. 2003. An intranet-based automated system for the surveillance of nosocomial infections: prospective validation compared with physicians' self-reports. Infect. Control Hosp. Epidemiol. 24:51–55.
    179.
    Voldstedlund M, Haarh M, and Molbak K. 2014. The Danish Microbiology Database (MiBa) 2010 to 2013. Euro Surveill. 19:20667. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20667.
    180.
    Buckeridge DL. 2007. Outbreak detection through automated surveillance: a review of the determinants of detection. J. Biomed. Inform. 40:370–379.
    181.
    Buehler JW, Berkelman RL, Hartley DM, and Peters CJ. 2003. Syndromic surveillance and bioterrorism-related epidemics. Emerg. Infect. Dis. 9:1197–1204.
    182.
    Carneiro HA and Mylonakis E. 2009. Google trends: a web-based tool for real-time surveillance of disease outbreaks. Clin. Infect. Dis. 49:1557–1564.
    183.
    Ortiz JR, Zhou H, Shay DK, Neuzil KM, Fowlkes AL, and Goss CH. 2011. Monitoring influenza activity in the United States: a comparison of traditional surveillance systems with Google Flu Trends. PLoS One 6:e18687.
    184.
    Tsui FC, Espino JU, Dato VM, Gesteland PH, Hutman J, and Wagner MM. 2003. Technical description of RODS: a real-time public health surveillance system. J. Am. Med. Inform. Assoc. 10:399–408.
    185.
    Milinovich GJ, Williams GM, Clements AC, and Hu W. 2014. Internet-based surveillance systems for monitoring emerging infectious diseases. Lancet Infect. Dis. 14:160–168.
    186.
    Harrison C, Jorder M, Stern H, Stavinsky F, Reddy V, Hanson H, Waechter H, Lowe L, Gravano L, and Balter S. 2014. Using online reviews by restaurant patrons to identify unreported cases of foodborne illness—New York City, 2012–2013. MMWR Morb. Mortal. Wkly. Rep. 63:441–445.
    187.
    Aarestrup FM, Brown EW, Detter C, Gerner-Smidt P, Gilmour MW, Harmsen D, Hendriksen RS, Hewson R, Heymann DL, Johansson K, Ijaz K, Keim PS, Koopmans M, Kroneman A, Lo Fo Wong D, Lund O, Palm D, Sawanpanyalert P, Sobel J, and Schlundt J. 2012. Integrating genome-based informatics to modernize global disease monitoring, information sharing, and response. Emerg. Infect. Dis. 18:e1.
    188.
    Shortliffe EH and Cimino JJ (ed). 2012. Biomedical informatics: computer applications in health care and biomedicine, 3rd ed. Springer, New York, NY.
    189.
    Ward-Cook KM, Lehmann CA, Schoeff LE, and Williams RH (ed). 2003. Clinical diagnostic technology. The total testing process, vol 1. AACC Press, Washington, DC.
    190.
    Ward-Cook KM, Lehmann CA, Schoeff LE, and Williams RH (ed). 2005. Clinical diagnostic technology. The total testing process, vol 2. AACC Press, Washington, DC.
    191.
    Ward-Cook KM, Lehmann CA, Schoeff LE, and Williams RH (ed). 2006. Clinical diagnostic technology. The total testing process, vol 3. AACC Press, Washington, DC.
    192.
    Sintchenko V (ed). 2010. Infectious disease informatics. Springer, New York, NY.
    193.
    Cowan D (ed). 2002. Informatics for the clinical laboratory: a practical guide for the pathologist. Springer, New York, NY.
    194.
    Campos JM. 2014. Chapter 24. The laboratory information system: making the most of it in the clinical microbiology laboratory, p 458–470. In Garcia LS (ed), Clinical laboratory management, 2nd ed. ASM Press, Washington, DC.
    195.
    Pantanowitz L, Tuthill JM, and Balis UGJ (ed). 2012. Pathology informatics: theory and practice. ASCP Press, Chicago, IL.
    196.
    Pantanowitz L and Parwani AV (ed). 2014. Practical informatics for cytopathology. Springer, New York, NY.
    197.
    Sinard JH. 2006. Practical pathology informatics: demystifying informatics for the practicing anatomic pathologist. Springer, New York, NY.
    198.
    Hoyt RE and Yoshihashi AK (ed). 2014. Health informatics. Practical guide for healthcare and information technology professionals, 6th ed. Lulu, Raleigh, NC.
    199.
    Magnuson JA and Fu PC Jr (ed). 2014. Public health informatics and information systems, 2nd ed. Springer, New York, NY.
    200.
    CLSI. 2005. AUTO02-A2. Laboratory automation: bar codes for specimen container identification. CLSI, Wayne, PA.
    201.
    CLSI. 2009. AUTO03-A2. Laboratory automation: communications with automated clinical laboratory systems, instruments, devices, and information systems. CLSI, Wayne, PA.
    202.
    CLSI. 2006. AUTO08-A. Managing and validating laboratory information systems. CLSI, Wayne, PA
    203.
    Centers for Medicare & Medicaid Services (CMS), HHS, Centers for Disease Control and Prevention (CDC), HHS, Office for Civil Rights (OCR), HHS. 6 February 2014. CLIA program and HIPAA privacy rule; patients' access to test reports. Final rule. Fed. Regist. 79:7289–7316.
    204.
    American Telemedicine Association. 2014. Clinical guidelines for telepathology. American Telemedicine Association, Washington, DC.
    205.
    College of American Pathologists. 2013. Digital pathology resource guide, version 4.0. College of American Pathologists, Northfield, IL.
    206.
    Federal Register. 24 August 1998. Publication of OIG compliance program guidance for clinical laboratories—HHS. Fed. Regist. 63:45076–45087.
    207.
    Harris D, Khan L, Paul R, and Thuraisingham B. 2007. Standards for secure data sharing across organizations. Comput. Stand. Interfaces 29:86–96.
    208.
    Lowe A, Chlipala E, Elin J, Kawano Y, Long RE, and Tillman D. 2011. Validation of digital pathology in a healthcare environment. Digital Pathology Association, Madison, WI.

    Author Bios

    Daniel D. Rhoads [email protected]
    Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    Daniel D. Rhoads is a Chief Resident who is training in clinical pathology at the University of Pittsburgh Medical Center. In 2004, he received a B.S. in biology from Millersville University of Pennsylvania and completed medical technology training at Lancaster General College of Nursing and Health Sciences. In 2006, Dan began working as a research scientist at the Southwest Regional Wound Care Center and the Research and Testing Laboratory in Lubbock, TX. While studying chronic wounds there, he acquired his interest in biofilm infections and his desire to unravel the complexity of microbial communities by using informatics tools. In 2012, Dan received his M.D. from Texas Tech University Health Sciences Center, and he has recently taken coursework in the Department of Biomedical Informatics at the University of Pittsburgh. Dan has accepted a Medical Microbiology Fellowship at the Cleveland Clinic for the 2015–2016 academic year.
    Vitali Sintchenko
    Marie Bashir Institute for Infectious Diseases and Biosecurity and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
    Centre for Infectious Diseases and Microbiology-Public Health, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, New South Wales, Australia
    Vitali Sintchenko is a tenured Associate Professor of the Sydney Medical School at the University of Sydney and Director of the Centre for Infectious Diseases and Microbiology-Public Health at Westmead Hospital in Sydney, Australia. He is a Fellow of the Royal College of Pathologists of Australasia and earned his Ph.D. in medical informatics from the University of New South Wales. He is a member of the Marie Bashir Institute for Infectious Diseases and Biosecurity. His research focuses on infectious disease informatics, bacterial genomics-guided public health laboratory surveillance, and disease control. He has authored two books and more than 150 scientific papers. He has been actively involved in disease outbreak investigations and the design of biosurveillance systems. He currently chairs the Public Health Laboratory Network of Australia.
    Carol A. Rauch
    Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Carol A. Rauch received her M.D. and Ph.D. at Johns Hopkins University and continued her education with residency training in pathology and laboratory medicine and fellowship training in medical microbiology at Yale New Haven Hospital. At Baystate Health, the Western Campus of Tufts University School of Medicine, her roles included Medical Director of Clinical Microbiology, Chief of Clinical Pathology, and Medical Director of Laboratory Information Systems. She is currently Medical Director of Clinical Pathology and Associate Professor of Pathology, Microbiology & Immunology at Vanderbilt University School of Medicine. She recently chaired Division C for ASM. Through 20 years in clinical laboratories and clinical microbiology, her interests have included patient safety, quality in laboratory testing, and bioterrorism preparedness. Her professional experience has led to an appreciation of the critical role of pathology informatics in healthcare, as well as the special needs of microbiology in information systems as drivers of quality medical and public health information.
    Liron Pantanowitz
    Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    Liron Pantanowitz is an Associate Professor in the Departments of Pathology and Biomedical Informatics at the University of Pittsburgh. Dr. Pantanowitz obtained his M.D. in South Africa and specialized in pathology at Harvard University in Boston, MA. He subsequently completed cytopathology and hematopathology fellowships. Dr. Pantanowitz is currently the Director of Cytopathology at the University of Pittsburgh Medical Center (UPMC) Shadyside. He is also the Director of the Pathology Informatics Fellowship and Associate Director of the Pathology Informatics Division at UPMC. He is the immediate Past President of the Association for Pathology Informatics (API), and he has also served on several key committees for other societies, such as the CAP, ASCP, USCAP, and ATA. He has published many peer-reviewed articles and book chapters, written several textbooks, and given talks around the world. Dr. Pantanowitz is current Editor-in-Chief of the Journal of Pathology Informatics.

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    Clinical Microbiology Reviews
    Volume 27Number 4October 2014
    Pages: 1025 - 1047

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    Daniel D. Rhoads [email protected]
    Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    Vitali Sintchenko
    Marie Bashir Institute for Infectious Diseases and Biosecurity and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
    Centre for Infectious Diseases and Microbiology-Public Health, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, New South Wales, Australia
    Carol A. Rauch
    Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Liron Pantanowitz
    Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

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  • Clinical Microbiology ReviewsArticle
    Leptospirosis

    Abstract

    SUMMARY

    Leptospirosis is a worldwide zoonotic infection with a much greater incidence in tropical regions and has now been identified as one of the emerging infectious diseases. The epidemiology of leptospirosis has been modified by changes in animal husbandry, climate, and human behavior. Resurgent interest in leptospirosis has resulted from large outbreaks that have received significant publicity. The development of simpler, rapid assays for diagnosis has been based largely on the recognition that early initiation of antibiotic therapy is important in acute disease but also on the need for assays which can be used more widely. In this review, the complex taxonomy of leptospires, previously based on serology and recently modified by a genotypic classification, is discussed, and the clinical and epidemiological value of molecular diagnosis and typing is also evaluated.

    REFERENCES

    1.
    Abdulkader R., Sabbaga E., Meireles L., and Radu A.Vascular injury in acute renal failure due to leptospirosis is not associated with antineutrophil cytoplasmic antibody.Nephron651993156
    2.
    Abdulkader R. C. R. M.Acute renal failure in leptospirosis.Renal Fail.191997191198
    3.
    Adachi Y. and Yanagawa R.Inhibition of leptospiral agglutination by the type-specific main antigens of leptospiras.Infect. Immun.171977466467
    4.
    Adler B., Chappel R. J., and Faine S.The sensitivities of different immunoassays for detecting leptospiral antigen.Zentbl. Bakteriol.2521982405413
    5.
    Adler B., Cousins D. V., Faine S., and Robertson G. M.Bovine IgM and IgG response to Leptospira interrogans serovar hardjo as measured by enzyme immunoassay.Vet. Microbiol.71982577585
    6.
    Adler B. and Faine S.The antibodies involved in the human immune response to leptospiral infection.J. Med. Microbiol.111978387400
    7.
    Adler B. and Faine S.Host immunological mechanisms in the resistance of mice to leptospiral infections.Infect. Immun.1719776772
    8.
    Adler B., Faine S., Christopher W. L., and Chappel R. J.Development of an improved selective medium for isolation of leptospires from clinical material.Vet. Microbiol.121986377381
    9.
    Adler B., Faine S., and Gordon L. M.The enzyme-linked immunosorbent assay (ELISA) as a serological test for detecting antibodies against Leptospira interrogans serovar hardjo in sheep.Aust. Vet. J.571981414417
    10.
    Adler B., Faine S., and Yanagawa R.Comparative studies on two antigens (F4 and TM) extracted from leptospires.J. Clin. Microbiol.12198079
    11.
    Adler B., Murphy A. M., Locarnini S. A., and Faine S.Detection of specific anti-leptospiral immunoglobulins M and G in human serum by solid-phase enzyme-linked immunosorbent assay.J. Clin. Microbiol.111980452457
    12.
    Adler B. A. and Faine S.A Pomona serogroup-specific, agglutinating antigen in Leptospira, identified by monoclonal antibodies.Pathology151983247250
    13.
    Adler B. A. and Faine S.Species- and genus-specific antigens in Leptospira, revealed by monoclonal antibodies and enzyme immunoassay.Zentbl. Bakteriol.2551983317322
    14.
    Agrawal P. K. and Srivastava D. K.Outbreak of Weil's disease in a food fad commune in India.BMJ293198616461647
    15.
    Alani F. S. S., Mahoney M. P., Ormerod L. P., Wright P. A., and Garrues M.Leptospirosis presenting as atypical pneumonia, respiratory failure and pyogenic meningitis.J. Infect.271993281283
    16.
    Alexander A., Baer A., Fair J. R., Gochenour W. S., King J. H., and Yager R. N.Leptospiral uveitis: report of a bacteriologically confirmed case.Arch. Ophthalmol.481952292297
    17.
    Alexander A. D.Serological diagnosis of leptospirosisManual of clinical laboratory immunology3rd ed.Rose N. R., Friedman H., and Fahey J. L.1986435439American Society for MicrobiologyWashington, D.C.
    18.
    Alexander A. D., Benenson A. S., Byrne R. J., Dı́az-Rivera R. S., Evans L. B., Gochenour W. S., Hall H. E., Hightower J. A., Jeffries H., de Jesús J., Martı́nez E., Paniagua M., Pons J. A., Ramos-Morales F., Rodrı́guez-Molina R., Swisher K. Y., Woodward T. E., and Yager R. H.Leptospirosis in Puerto Rico.Zoonoses Res.21963152227
    19.
    Alexander A. D., Evans L. B., Baker M. F., Baker H. J., Ellison D., and Marriapan M.Pathogenic leptospiras isolated from Malaysian surface waters.Appl. Microbiol.2919753033
    20.
    Alexander A. D., Lessel E. F., Evans L. B., Franck E., and Green S. S.Preservation of leptospiras by liquid-nitrogen refrigeration.Int. J. Syst. Bacteriol.221972165169
    21.
    Alexander A. D. and Rule P. L.Penicillins, cephalosporins, and tetracyclines in treatment of hamsters with fatal leptospirosis.Antimicrob. Agents Chemother.301986835839
    22.
    Allen P., Raftery S., and Phelan D.Massive pulmonary haemorrhage due to leptospirosis.Intensive Care Med.151989322324
    23.
    Alston J. M.Leptospiral jaundice among sewer-workers.Lanceti1935806809
    24.
    Alston J. M. and Broom J. C.Leptospirosis in man and animals. E. & S.1958LivingstoneEdinburgh, U.K
    25.
    Anderson B. S. and Minette H. P.Leptospirosis in Hawaii: shifting trends in exposure, 1907–1984.Int. J. Zoonoses1319867688
    26.
    Anderson D. C., Folland D. S., Fox M. D., Patton C. M., and Kaufmann A. F.Leptospirosis: a common-source outbreak due to leptospires of the grippotyphosa serogroup.Am. J. Epidemiol.1071978538544
    27.
    Anderson D. C., Geistfeld J. G., Maetz H. M., Patton C. M., and Kaufmann A. F.Leptospirosis in zoo workers associated with bears.Am. J. Trop. Med. Hyg.271978210211
    28.
    Andreescu N., Tacorian D., Duminica E., Filip M., and Sosin A.Investigarea serologica in complicatiile oculare ale leptospirozelor la om.Bacteriol. Virusol. Parazitol. Epidemiol.3319884146
    29.
    André-Fontaine G., Peslerbe X., and Ganiere J. P.Occupational hazard of unnoticed leptospirosis in water ways maintenance staff.Eur. J. Epidemiol.81992228232
    30.
    Andrew D. E. and Marrocco G. R.Leptospirosis in New England.JAMA238197720272028
    31.
    Annear D. I.Recovery of leptospires after dry storage for ten years.Int. J. Syst. Bacteriol.241974399401
    32.
    Antoniadis A., Alexiou-Daniel S., Fidani L., and Bautz E. F. K.Comparison of the clinical and serologic diagnosis of haemorrhagic fever with renal syndrome (HFRS) and leptospirosis.Eur. J. Epidemiol.1119959192
    33.
    Appassakij H., Silpapojakul K., Wansit R., and Woodtayakorn J.Evaluation of the immunofluorescent antibody test for the diagnosis of human leptospirosis.Am. J. Trop. Med. Hyg.521995340343
    34.
    Areán V. M.Leptospiral myocarditis.Lab. Investig.61957462471
    35.
    Areán V. M.The pathologic anatomy and pathogenesis of fatal human leptospirosis (Weil's disease).Am. J. Pathol.401962393423
    36.
    Areán V. M., Sarasin G., and Green J. H.The pathogenesis of leptospirosis: toxin production by Leptospira icterohaemorrhagiae.Am. J. Vet. Res.251964836843
    37.
    Arimitsu Y., Fukumura K., and Shintaki Y.Distribution of leptospirosis among stray dogs in the Okinawa Islands, Japan: comparison of the microcapsule and microscopic agglutination tests.Br. Vet. J.1451989473477
    38.
    Arimitsu Y., Kmety E., Ananyina Y., Baranton G., Ferguson I. R., Smythe L., and Terpstra W. J.Evaluation of the one-point microcapsule agglutination test for diagnosis of leptospirosis.Bull. WHO721994395399
    39.
    Arimitsu Y., Kobayashi S., Akama K., and Matuhasi T.Development of a simple serological method for diagnosing leptospirosis: a microcapsule agglutination test.J. Clin. Microbiol.151982835841
    40.
    Arimitsu Y., Matuhasi T., Kobayashi S., Sato T., and Cui J. J.Serodiagnosis of leptospirosis in China by the one-point MCA method.Epidemiol. Infect.991987393398
    41.
    Awad-Masalmeh A. and Willinger H.Evaluation of 2-mercapto-ethanol treatment in serodiagnosis of swine leptoispirosis.Microbiologica61983133143
    42.
    Baber M. D. and Stuart R. D.Leptospirosis canicola: a case treated with penicillin.Lancetii1946594596
    43.
    Babudieri B.Animal reservoirs of leptospirosis.Ann. N.Y. Acad. Sci.701958393413
    44.
    Baelen E. and Roustan J.Leptospirosis associated with acute acalculous cholecystitis.J. Clin. Gastroenterol.251997704706
    45.
    Bahaman A. R., Ibrahim A. L., Stallman N. D., and Tinniswood R. D.The bacteriological prevalence of leptospiral infection in cattle and buffaloes in West Malaysia.Epidemiol. Infect.1001988239246
    46.
    Bal A. E., Gravekamp C., Hartskeerl R. A., de Meza-Brewster J., Korver H., and Terpstra W. J.Detection of leptospires in urine by PCR for early diagnosis of leptospirosis.J. Clin. Microbiol.32199418941898
    47.
    Ballard S. A., Segers R. P. A. M., Bleumink-Pluym N., Fyfe J., Faine S., and Adler B.Molecular analysis of the hsp (groE) operon of Leptospira interrogans serovar copenhageni.Mol. Microbiol.81993739751
    48.
    Ballard S. A., Williamson M., Adler B., Vinh T., and Faine S.Interactions of virulent and avirulent leptospires with primary cultures of renal epithelial cells.J. Med. Microbiol.2119865967
    49.
    Banfi E., Cinco M., Bellini M., and Soranzo M. R.The role of antibodies and serum complement in the interaction between macrophages and leptospires.J. Gen. Microbiol.1281982813816
    50.
    Banfi E., Cinco M., Delia S., Castagnari L., Vullo V., Mastroianni C. M., and Contini C.New trends in the rapid serodiagnosis of leptospirosis.Zentbl. Bakteriol.2571984503507
    51.
    Baril C., Herrmann J. L., Richaud C., Margarita D., and Girons I. S.Scattering of the rRNA genes on the physical map of the circular chromosome of Leptospira interrogans serovar icterohaemorrhagiae.J. Bacteriol.174199275667571
    52.
    Baril C. and Saint Girons I.Sizing of the Leptospira genome by pulsed-field agarose gel electrophoresis.FEMS Microbiol. Lett.71199095100
    53.
    Barkay S. and Garzozi H.Leptospirosis and uveitis.Ann. Ophthalmol.161984164168
    54.
    Barkin R. M. and Glosser J. W.Leptospirosis—an epidemic in children.Am. J. Epidemiol.981973184191
    55.
    Barkin R. M., Guckian J. C., and Glosser J. W.Infection by Leptospira ballum: a laboratory-associated case.South. Med. J.671974155156
    56.
    Barnett J. K., Barnett D., Bolin C. A., Summers T. A., Wagar E. A., Cheville N. F., Hartskeerl R. A., and Haake D. A.Expression and distribution of leptospiral outer membrane components during renal infection of hamsters.Infect. Immun.671999853861
    57.
    Beeson P. B. and Hankey D. D.Leptospiral meningitis.Arch. Intern. Med.891952575583
    58.
    Bercovich Z., Taaijke R., and Bokhout B. A.Evaluation of an ELISA for the diagnosis of experimentally induced and naturally occurring Leptospira hardjo infections in cattle.Vet. Microbiol.211990255262
    59.
    Berendsen H. H., Rommes J. H., Hylkema B. S., Meinesz A. F., and Sluiter H. J.Adult respiratory failure with leptospirosis.Ann. Intern. Med.1011984402
    60.
    Berg H. C., Bromley D. B., and Charon N. W.Leptospiral motilityRelations between structure and function in the prokaryotic cell. 28th Symposium of the Society for General Microbiology.Stanier R. Y., Rogers H. J., and Ward J. B.1978285294Cambridge University PressCambridge, U.K
    61.
    Berman S. J., Tsai C. C., Holmes K. K., Fresh J. W., and Watten R. H.Sporadic anicteric leptospirosis in South Vietnam.Ann. Intern. Med.791973167173
    62.
    Bernheimer A. W. and Bey R. F.Copurification of Leptospira interrogans serovar pomona hemolysin and sphingomyelinase C.Infect. Immun.541986262264
    63.
    Bethlem N., Lemle A., and Pereira N. G.Leptospirosis.Semin. Respir. Med.1219915867
    64.
    Bey R. F. and Johnson R. C.Protein-free and low-protein media for the cultivation of Leptospira.Infect. Immun.191978562569
    65.
    Blackmore D. K., Bell L., and Schollum L.Leptospirosis in meat inspectors: preliminary results of a serological survey.N. Z. Med. J.901979415418
    66.
    Blackmore D. K. and Schollum L. M.Risks of contracting leptospirosis on the dairy farm.N. Z. Med. J.951982649652
    67.
    Blackmore D. K., Schollum L. M., and Moriarty K. M.The magnitude and duration of titres of leptospiral agglutinins in human sera.N. Z. Med. J.9719848386
    68.
    Blagoveshchenskaia N. M.On the epidemiology of anicteric leptospirosis.J. Microbiol. Epidemiol. Immunobiol.281957240244
    69.
    Bolin C.LeptospirosisEmerging diseases of animals.Brown C. and Bolin C.2000185200ASM PressWashington, D.C.
    70.
    Bolin C. A. and Koellner P.Human-to-human transmission of Leptospira interrogans by milk.J. Infect. Dis.1581988246247
    71.
    Bolin C. A. and Zuerner R. L.Correlation between DNA restriction fragment length polymorphisms in Leptospira interrogans serovar pomona type kennewicki and host animal source.J. Clin. Microbiol.341996424425
    72.
    Bolin C. A., Zuerner R. L., and Trueba G.Comparison of three techniques to detect Leptospira interrogans serovar hardjo type hardjo-bovis in bovine urine.Am. J. Vet. Res.50198910011003
    73.
    Boursaux-Eude C., Saint Girons I., and Zuerner R. L.IS1500, an IS3-like element from Leptospira interrogans.Microbiology141199521652173
    74.
    Boursaux-Eude C., Saint Girons I., and Zuerner R. L.Leptospira genomics.Electrophoresis191998589592
    75.
    Bowdoin C. D.A new disease identity (?).J. Med. Assoc. Ga.311942437442
    76.
    Bragger J. M. and Adler B.A card test for the serodiagnosis of human leptospirosis.J. Clin. Pathol.291976198202
    77.
    Brandão A. P., Camargo E. D., da Silva E. D., Silva M. V., and Abrão R. V.Macroscopic agglutination test for rapid diagnosis of human leptospirosis.J. Clin. Microbiol.36199831383142
    78.
    Brandling-Bennett A. D. and Pinheiro F.Infectious diseases in Latin America and the Caribbean: are they really emerging and increasing?Emerg. Infect. Dis.219965961
    79.
    Braun J. L.Epidemiology of leptospirosis in Iowa-a study of sporadic and epidemic cases.J. Am. Vet. Med. Assoc.1381961532536
    80.
    Brendle J. J., Rogul M., and Alexander A. D.Deoxyribonucleic acid hybridization among selected leptospiral serotypes.Int. J. Syst. Bacteriol.241974205214
    81.
    Brenner D. J., Kaufmann A. F., Sulzer K. R., Steigerwalt A. G., Rogers F. C., and Weyant R. S.Further determination of DNA relatedness between serogroups and serovars in the family Leptospiraceae with a proposal for Leptospira alexanderi sp. nov. and four new Leptospira genomospecies.Int. J. Syst. Bacteriol.491999839858
    82.
    Broughton E. S. and Scarnell J.Prevention of renal carriage of leptospirosis in dogs by vaccination.Vet. Rec.1171985307311
    83.
    Brown C. A., Roberts A. W., Miller M. A., David D. A., Brown S. A., Bolin C. A., Jarecki-Black J., Greene C. E., and Miller-Liebl D.Leptospira interrogans serovar grippotyphosa infection in dogs.J. Am. Vet. Med. Assoc.209199612651267
    84.
    Brown P. D., Gravekamp C., Carrington D. G., Van de Kemp H., Hartskeerl R. A., Edwards C. N., Everard C. O. R., Terpstra W. J., and Levett P. N.Evaluation of the polymerase chain reaction for early diagnosis of leptospirosis.J. Med. Microbiol.431995110114
    85.
    Brown P. D. and Levett P. N.Differentiation of Leptospira species and serovars by PCR-restriction endonuclease analysis, arbitrarily primed PCR and low-stringency PCR.J. Med. Microbiol.461997173181
    86.
    Buchanan G.Spirochaetal jaundice. Special Report Series, no. 113.1927Medical Research Council, London, U.K.
    87.
    Buckland F. E. and Stuart R. D.Mud fever (leptospirosis) in the British army in France.Lancetii1945331333
    88.
    Bulach D. M., Kalambaheti T., de La Peña-Moctezuma A., and Adler B.Functional analysis of genes in the rfb locus of Leptospira borgpetersenii serovar hardjo subtype hardjobovis.Infect. Immun.68200037933798
    89.
    Burke B. J., Searle J. F., and Mattingly D.Leptospirosis presenting with profuse haemoptysis.BMJ21976982
    90.
    Burth P., Younes-Ibrahim M., Gonçalez F. H. F. S., Costa E. R., and Castro Faria M. V.Purification and characterization of a Na+, K+ ATPase inhibitor found in an endotoxin of Leptospira interrogans.Infect. Immun.6519971571560
    91.
    Butler C. S. and Endara S. A.Leptospirosis complicated by severe aortic stenosis.Anaesth. Intensive Care282000434437
    92.
    Cacciapuoti B., Ciceroni L., Maffei C., Di Stanislao F., Strusi P., Calegari L., Lupido R., Scalise G., Cagnoni G., and Renga G.A waterborne outbreak of leptospirosis.Am. J. Epidemiol.1261987535545
    93.
    Caccione R. A., Cascelli E. S., Saravı́ M. A., and Martı́nez E. S.Brote de leptospirosis en niños de Longhamps, Pcia de Buenos Aires, Argentina: daignostico de laboratorio.Rev. Argent. Microbiol.91977126128
    94.
    Camargo E. D., Silva M. V., Vaz A. J., Batista L., Brandão A. P., Ferreira A. W., Romero E. C., and Barbosa P. R. S.ELISA-IgM applied to cerebrospinal fluid in human leptospirosis.Serodiagn. Immunother. Infect. Dis.719951922
    95.
    Campagnolo E. R., Warwick M. C., Marx H. L., Cowart R. P., Donnell H. D., Bajani M. D., Bragg S. L., Esteban J. E., Alt D. P., Tappero J. W., Bolin C. A., and Ashford D. A.Analysis of the 1998 outbreak of leptospirosis in Missouri in humans exposed to infected swine.J. Am. Vet. Med. Assoc.2162000676682
    96.
    Cargill W. H. and Beeson P. B.The value of spinal fluid examination as a diagnostic procedure in Weil's disease.Ann. Intern. Med.271947396400
    97.
    Centers for Disease Control and PreventionCase definitions for infectious conditions under public health surveillance.Morb. Mortal. Wkly. Rep.46RR-10199749
    98.
    Centers for Disease Control and PreventionOutbreak of acute febrile illness among athletes participating in triathlons—Wisconsin and Illinois, 1998.Morb. Mortal. Wkly. Rep.471998585588
    99.
    Centers for Disease Control and PreventionOutbreak of acute febrile illness among participants in EcoChallenge Sabah 2000—Malaysia, 2000.Morb. Mortal. Wkly. Rep.492000816817
    100.
    Centers for Disease Control and PreventionOutbreak of acute febrile illness and pulmonary hemorrhage—Nicaragua, 1995.Morb. Mortal. Wkly. Rep.441995841843
    101.
    Centers for Disease Control and PreventionSummary of notifiable diseases, United States 1994.Morb. Mortal. Wkly. Rep.43531994180
    102.
    Centers for Disease Control and PreventionUpdate: leptospirosis and unexplained acute febrile illness among athletes participating in triathlons—Illinois and Wisconsin, 1998.Morb. Mortal. Wkly. Rep.471998673676
    103.
    Champagne M. J., Higgins R., Fairbrother J. M., and Dubreuil D.Detection and characterization of leptospiral antigens using a biotin/avidin double-antibody sandwich enzyme-linked immunosorbent assay and immunoblot.Can. J. Vet. Res.551991239245
    104.
    Chan O. Y., Paul D. R., and Sng E. H.Leptospirosis among abattoir workers—a serological study.Singapore Med. J.281987293296
    105.
    Chang R. S., Smith D. J. W., McComb D. E., Sharp C. F., and Tonge J. I.The use of erythrocyte sensitizing substance in the diagnosis of leptospiroses. II. The sensitized erythrocyte lysis test.Am. J. Trop. Med. Hyg.61957101107
    106.
    Chang S. L., Buckingham M., and Taylor M. P.Studies on Leptospira icterohaemorrhagiae. IV. Survival in water and sewage: destruction in water by halogen compounds, synthetic detergents, and heat.J. Infect. Dis.821948256266
    107.
    Chapman A. J., Adler B., and Faine S.Antigens recognised by the human immune repsonse to infection with Leptospira interrogans serovar hardjo.J. Med. Microbiol.251988269278
    108.
    Chapman A. J., Adler B., and Faine S.Genus-specific antigens in Leptospira revealed by immunoblotting.Zentbl. Bakteriol.2641987279283
    109.
    Chappel R. J., Adler B., Ballard S. A., Faine S., Jones R. T., Millar B. D., and Swainger J. A./85. Enzymatic radioimmunoassay for detecting Leptospira interrogans serovar pomona in the urine of experimentally-infected pigs.Vet. Microbiol.101984279286
    110.
    Chee H. D., Ossenkoppele G. J., Bronsveld W., and Thijs L. G.Adult respiratory distress syndrome in Leptospira icterohaemorragiae infection.Intensive Care Med.111985254256
    111.
    Chen T.Development and present status of leptospiral vaccine and technology of vaccine production in China.Jpn. J. Bacteriol.401985755762
    112.
    Chernukha Y. G., Shishkina Z. S., Baryshev P. M., and Kokovin I. L.The dynamics of IgM- and IgG-antibodies in leptospiral infection in man.Zentbl. Bakteriol.2361976336343
    113.
    Christopher W. L., Adler B., and Faine S.Immunogenicity of leptospiral vaccines grown in protein-free medium.J. Med. Microbiol.151982493501
    114.
    Chu K. M., Rathinam R., Namperumalsamy P., and Dean D.Identification of Leptospira species in the pathogenesis of uveitis and determination of clinical ocular characteristics in South India.J. Infect. Dis.177199813141321
    115.
    Chung H.-L., Ch'iu F.-H., Wu H.-T., Hou T.-C., and K'uang C.-H.Leptospirosis. A clinical and statistical study of 182 cases.Chin. Med. J.771958207235
    116.
    Chung H.-L., Ts'ao W.-C., Mo P.-S., and Yen C.Transplacental or congenital infection of leptospirosis.Chin. Med. J.821963777782
    117.
    Cinco M. and Banfi E.Interactions between human polymorphonuclear leukocytes and one strain of pathogenic Leptospira (L. interrogans sp.) and one of saprophytic Leptospira (L. biflexa sp.).FEMS Microbiol. Lett.1919835154
    118.
    Cinco M., Banfi E., and Soranzo M. R.Studies on the interaction between macrophages and leptospires.J. Gen. Microbiol.1241981409413
    119.
    Cinco M., Banfi M., Furlani A., and Scarcia V.Cytotoxic activity of supernatant extracts of virulent and saprophytic leptospires.Zentbl. Bakteriol.2481980260267
    120.
    Cockburn T. A., Vavra J. D., Spencer S. S., Dann J. R., Peterson L. J., and Reinhard K. R.Human leptospirosis associated with a swimming pool, diagnosed after eleven years.Am. J. Hyg.60195417
    121.
    Coggins W. J.Leptospirosis due to Leptospira pomona. An outbreak of nine cases.JAMA181196210771078
    122.
    Coghlan J. D. and Bain A. D.Leptospirosis in human pregnancy followed by death of the foetus.BMJ11969228230
    123.
    Cole J. R., Sangster L. T., Sulzer C. R., Pursell A. R., and Ellinghausen H. C.Infections with Encephalitozoon cuniculi and Leptospira interrogans, serovars grippotyphosa and ballum, in a kennel of foxhounds.J. Am. Vet. Med. Assoc.1801982435437
    124.
    Cole J. R., Sulzer C. R., and Pursell A. R.Improved microtechnique for the leptospiral microscopic agglutination test.Appl. Microbiol.251973976980
    125.
    Collares-Pereira M., Cristino J. A. G. M., and Pereira A. T.Plasmid analysis of LeptospiraLeptospirosis. Proceedings of the Leptospirosis Research Conference 1990.Kobayashi Y.1991462473University of Tokyo PressTokyo, Japan
    126.
    Communicable Disease Surveillance CentreLeptospirosis outbreak in Eco Challenge 2000 participants.Commun. Dis. Rep.102000341
    127.
    Constantin A., Marin F., Oksman F., and Bouteiller G.Antineutrophil cytoplasmic antibodies in leptospirosis.J. Rheumatol.231996411
    128.
    Corney B. G., Colley J., Djordjevic S. P., Whittington R., and Graham G. C.Rapid identification of some Leptospira isolates from cattle by random amplified polymorphic DNA fingerprinting.J. Clin. Microbiol.31199329272932
    129.
    Corney B. G., Colley J., and Graham G. C.Simplified analysis of pathogenic leptospiral serovars by random amplified polymorphic DNA fingerprinting.J. Med. Microbiol.461997927932
    130.
    Corwin A., Ryan A., Bloys W., Thomas R., Deniega B., and Watts D.A waterborne outbreak of leptospirosis among United States military personnel in Okinawa, Japan.Int. J. Epidemiol.191990743748
    131.
    Costa S. and Troisier J.Un cas de spirochétose ictéro-hémorragique.Bull. Mém. Soc. Méd. Hôpitaux de Paris40191616351639
    132.
    Cotter T. J.Weil's disease in North Queensland.BMJ119365156
    133.
    Coursin D. B., Updike S. J., and Maki D. G.Massive rhabdomyolysis and multiple organ dysfunction syndrome caused by leptospirosis.Intensive Care Med.262000808812
    134.
    Cousins D. V., Robertson G. M., and Hustas L.The use of the enzyme-linked immunosorbent assay (ELISA) to detect the IgM and IgG antibody response to Leptospira interrogans serovars hardjo, pomona and tarassovi in cattle.Vet. Microbiol.101985439450
    135.
    Cox C. D.Hemolysis of sheep erythrocytes sensitized with leptospiral extracts.Proc. Soc. Exp. Biol. Med.901955610615
    136.
    Cox C. D., Alexander A. D., and Murphy L. C.Evaluation of the hemolytic test in the serodiagnosis of human leptospirosis.J. Infect. Dis.1011957210218
    137.
    Crawford R. P., Heinemann J. M., McCulloch W. F., and Diesch S. L.Human infections associated with waterborne leptospires, and survival studies on serotype pomona.J. Am. Vet. Med. Assoc.159197114771484
    138.
    Crawford S. M. and Miles D. W.Leptospira hebdomadis associated with an outbreak of illness in workers on a farm in North Yorkshire.Br. J. Ind. Med.371980397398
    139.
    Cui J. J., Xiao G. X., Chen T. Z., Zhu G. F., Sato T., Seki M., Kobayahsi S., and Arimitsu Y.Further evaluation of one-point microcapsule agglutination test for diagnosis of leptospirosis.Epidemiol. Infect.1061991561565
    140.
    Cumberland P. C., Everard C. O. R., and Levett P. N.Assessment of the efficacy of the IgM enzyme-linked immunosorbent assay (ELISA) and microscopic agglutination test (MAT) in the diagnosis of acute leptospirosis.Am. J. Trop. Med. Hyg.611999731734
    141.
    Daher E., Zanetta D. M., Cavalcante M. B., and Abdulkader R. C.Risk factors for death and changing patterns in leptospirosis acute renal failure.Am. J. Trop. Med. Hyg.611999630634
    142.
    Dai B., Xiao J., and Shen C.Identification of pathogenic leptospires by recombinant DNA probes.Chin. Med. Sci. J.91994209214
    143.
    da Silva M. V., Batista L., Camargo E. D., Leitao P. A., Szalkay V. G., Rosenthal C., Vaz A. J., and de Souza A. M.Leptospirosis in patients with anti-HIV antibodies: report of 2 cases.Rev. Soc. Bras. Med. Trop.231990229231
    144.
    Davenport A., Rugman F. P., Desmond M. J., and Ganta R.Is thrombocytopenia seen in patients with leptospirosis immunologically mediated?J. Clin. Pathol.421989439440
    145.
    Dawson B. and Hume W. E.Jaundice of infective origin.Q. J. Med.10191690131
    146.
    De Biase L., De Curtis G., Paparoni S., Sciarra D., and Campa P. P.Fatal leptospiral myocarditis.G. Ital. Cardiol.171987992994
    147.
    de Brito T., Freymüller E., Penna D. O., Santos H. S., Soares de Almeida S., Galvão P. A. A., and Pereira V. G.Electron microscopy of the biopsied kidney in human leptospirosis.Am. J. Trop. Med. Hyg.141965397403
    148.
    de Brito T., Machado M. M., Montans S. D., Hosino S., and Freymüller E.Liver biopsy in human leptospirosis: a light and electron microscopy study.Virchows Arch. Pathol. Anat.34219676169
    149.
    de Brito T., Morais C. F., Yasuda P. H., Lancellotti C. P., Hoshino-Shimizu S., Yamashiro E., and Alves V. A. F.Cardiovascular involvement in human and experimental leptospirosis: pathologic findings and immunohistochemical detection of leptospiral antigen.Ann. Trop. Med. Parasitol.811987207214
    150.
    de Caballero O. L. S. D., Dias Neto E., Koury M. C., Romanha A. J., and Simpson A. J. G.Low-stringency PCR with diagnostically useful primers for identification of Leptospira serovars.J. Clin. Microbiol.32199413691372
    151.
    de Koning J., van der Hoeven J. G., and Meinders A. E.Respiratory failure in leptospirosis (Weil's disease).Neth. J. Med.471995224229
    152.
    de la Peña-Moctezuma A., Bulach D. M., Kalambaheti T., and Adler B.Comparative analysis of the LPS biosynthetic loci of the genetic subtypes of serovar Hardjo: Leptospira interrogans subtype Hardjoprajitno and Leptospira borgpetersenii subtype Hardjobovis.FEMS Microbiol. Lett.1771999319326
    153.
    de Lima S. C., Sakata E. E., Santo C. E., Yasuda P. H., Stiliano S. V., and Ribeiro F. A.Outbreak of human leptospirosis by recreational activity in the municipality of Sao Jose dos Campos, Sao Paulo: seroepidemiological study.Rev. Inst. Med. Trop. Sao Paulo321990474479
    154.
    del Real G., Segers R. P., van der Zeijst B. A., and Gaastra W.Cloning of a hemolysin gene from Leptospira interrogans serovar hardjo.Infect. Immun.57198925882590
    155.
    Demers R. Y., Frank R., Demers P., and Clay M.Leptospiral exposure in Detroit rodent control workers.Am. J. Public Health75198510901091
    156.
    Demers R. Y., Thiermann A., Demers P., and Frank R.Exposure to Leptospira icterohaemorrhagiae in inner-city and suburban children: a serologic comparison.J. Fam. Pract.17198310071011
    157.
    Derham R. L. J.Leptospirosis as a cause of erythema nodosum.BMJ21976403404
    158.
    de Souza D.Considerações sobre enchentes e leptospirose humana no municipio de São Paulo.Rev. Esc. Enferm. USP201986243250
    159.
    de Souza L. and Koury M. C.Chemical and biological properties of endotoxin from Leptospira interrogans serovars canicola and icterohaemorrhagiae.Braz. J. Med. Biol. Res.251992467475
    160.
    Diesch S. L.Survival of leptospires in cattle manure.J. Am. Vet. Med. Assoc.159197115131517
    161.
    Diesch S. L. and McCulloch W. F.Isolation of pathogenic leptospires from waters used for recreation.Public Health Rep.811966299304
    162.
    Dikken H. and Kmety E.Serological typing methods of leptospiresMethods in MicrobiologyBergan T. and Norris J. R.111978259307Academic PressLondon, U.K
    163.
    Ding M. and Yelton D. B.Cloning and analysis of the leuB gene of Leptospira interrogans serovar pomona.J. Gen. Microbiol.139199310931103
    164.
    Dinger J. E.Duurzaamheid der smetkracht van leptospirenkweeken.Ned. Tijdschr. Geneeskd.72193215111519
    165.
    Dive A. M., Bigaignon G., and Reynaert M.Adult respiratory distress syndrome in Leptospira icterohaemorrhagiae infection.Intensive Care Med.131987214
    166.
    Dobrina A., Nardon E., Vecile E., Cinco M., and Patriarca P.Leptospira icterohemorrhagiae and leptospire peptidoglycans induce endothelial cell adhesiveness for polymorphonuclear leukocytes.Infect. Immun.63199529952999
    167.
    Doeleman F. P. J.Ziekte van Weil, rechstreeks overgebracht van mensch op mensch.Ned. Tijdschr. Geneeskd.7619325057
    168.
    Doherty J. P., Adler B., Rood J. I., Billington S. J., and Faine S.Expression of two conserved leptospiral antigens in Escherichia coli.J. Med. Microbiol.281989143149
    169.
    Dooley J. R. and Ishak K. G.LeptospirosisPathology of tropical and extraordinary diseasesBinford C. H. and Connor D. H.11976101106 Armed Forces Institute of PathologyWashington, D.C.
    170.
    Douglin C. P., Jordan C., Rock R., Hurley A., and Levett P. N.Risk factors for severe leptospirosis in the parish of St. Andrew, Barbados.Emerg. Infect. Dis.319977880
    171.
    du Couëdic L., Courtin J. P., Poubeau P., Tanguy B., di Francia M., and Arvin-Berod C.Hémorragies intra-alvéolaires patentes et occultes au cours des leptospiroses.Rev. Mal. Respir.1519986167
    172.
    Dupont H., Dupont-Perdrizet D., Perie J. L., Zehner-Hansen S., Jarrige B., and Daijardin J. B.Leptospirosis: prognostic factors associated with mortality.Clin. Infect. Dis.251997720724
    173.
    Edelweiss E. L. and Mailloux M.The curve of immunoglobulins in human leptospirosis.Int. J. Zoonoses919825155
    174.
    Edwards C. N.Leptospirosis and pancreatitis.Pediatr. Infect. Dis. J.181999399400
    175.
    Edwards C. N. and Everard C. O. R.Hyperamylasemia and pancreatitis in leptospirosis.Am. J. Gastroenterol.86199116651668
    176.
    Edwards C. N., Nicholson G. D., and Everard C. O. R.Thrombocytopenia in leptospirosis.Am. J. Trop. Med. Hyg.311982827829
    177.
    Edwards C. N., Nicholson G. D., Hassell T. A., Everard C. O. R., and Callender J.Leptospirosis in Barbados: a clinical study.West Indian Med. J.3919902734
    178.
    Edwards C. N., Nicholson G. D., Hassell T. A., Everard C. O. R., and Callender J.Penicillin therapy in icteric leptospirosis.Am. J. Trop. Med. Hyg.391988388390
    179.
    Edwards C. N., Nicholson G. D., Hassell T. A., Everard C. O. R., and Callender J.Thrombocytopenia in leptospirosis: the absence of evidence for disseminated intravascular coagulation.Am. J. Trop. Med. Hyg.351986352354
    180.
    Edwards G. A. and Domm B. M.Human leptospirosis.Medicine391960117156
    181.
    Effler P. V., Domen H. Y., Bragg S. L., Aye T., and Sasaki D. M.Evaluation of the indirect hemagglutination assay for diagnosis of acute leptospirosis in Hawaii.J. Clin. Microbiol.38200010811084
    182.
    Elder J. K., Pepper P. M., Hill M. W. M., and Ward W. H.The significance of leptospiral titres associated with bovine abortion.Aust. Vet. J.621985258262
    183.
    Ellinghausen H. C.Growth, cultural characteristics, and antibacterial sensitivity of Leptospira interrogans serovar hardjo.Cornell Vet.731983225239
    184.
    Ellinghausen H. C. and McCullough W. G.Nutrition of Leptospira pomona and growth of 13 other serotypes: fractionation of oleic albumin complex and a medium of bovine albumin and polysorbate 80.Am. J. Vet. Res.2619654551
    185.
    Ellis W. A., Cassells J. A., and Doyle J.Genital leptospirosis in bulls.Vet. Rec.1181986333
    186.
    Ellis W. A., Hovind-Hougen K., Moller S., and Birch-Andresen A.Morphological changes upon subculturing of freshly isolated strains of Leptospira interrogans serovar hardjo.Zentralbl. Bakteriol. Mikrobiol. Hyg. A2551983323335
    187.
    Ellis W. A. and Michna S. W.Bovine leptospirosis: a serological and clinical study.Vet. Rec.991976387391
    188.
    Ellis W. A. and Michna S. W.Bovine leptospirosis: demonstration of leptospires of the Hebdomadis serogroup in aborted fetuses and a premature calf.Vet. Rec.991976430432
    189.
    Ellis W. A. and Michna S. W.Bovine leptospirosis: experimental infection of pregnant heifers with a strain belonging to the Hebdomadis serogroup.Res. Vet. Sci.221977229236
    190.
    Ellis W. A. and Michna S. W.Bovine leptospirosis: infection by the Hebdomadis serogroup and abortion-a herd study.Vet. Rec.991976409412
    191.
    Ellis W. A., Neill S. D., O'Brien J. J., Cassells J. A., and Hanna J.Bovine leptospirosis: microbiological and serological findings in normal fetuses removed from the uteri after slaughter.Vet. Rec.1101982192194
    192.
    Ellis W. A., O'Brien J. J., and Cassells J.Role of cattle in the maintenance of Leptospira interrogans serovar hardjo infection in Northern Ireland.Vet. Rec.1082000555557
    193.
    Ellis W. A., O'Brien J. J., Cassells J. A., Neill S. D., and Hanna J.Excretion of Leptospira interrogans serovar hardjo following calving or abortion.Res. Vet. Sci.391985296298
    194.
    Ellis W. A., O'Brien J. J., Neill S., Hanna J., and Bryson D. G.The isolation of a leptospire from an aborted bovine fetus.Vet. Rec.991976458459
    195.
    Ellis W. A., O'Brien J. J., Neill S. D., Ferguson H. W., and Hanna J.Bovine leptospirosis: microbiological and serological findings in aborted fetuses.Vet. Rec.1101982147150
    196.
    Ellis W. A., O'Brien J. J., Pearson J. K. L., and Collins D. S.Bovine leptospirosis: infection by the Hebdomadis serogroup and mastitis.Vet. Rec.991976368370
    197.
    Ellis W. A., Songer J. G., Montgomery J., and Cassells J. A.Prevalence of Leptospira interrogans serovar hardjo in the genital and urinary tracts of non-pregnant cattle.Vet. Rec.11819861113
    198.
    Ellis W. A. and Thiermann A. B.Isolation of leptospires from the genital tracts of Iowa cows.Am. J. Vet. Res.47198616941696
    199.
    Elwell M. R., Ward G. S., Hansukjariya P., and Tingpalapong M.Doxycycline prophylaxis for experimental leptospira infection in non-human primates and hamsters.Southeast Asian J. Trop. Med. Public Health.161985268273
    200.
    Emmanouilides C. E., Kohn O. F., and Garibaldi R.Leptospirosis complicated by a Jarisch-Herxheimer reaction and adult respiratory distress syndrome: case report.Clin. Infect. Dis.18199410041006
    201.
    Epstein P. R., Pena O. C., and Racedo J. B.Climate and disease in Colombia.Lancet346199512431244
    202.
    Estavoyer J.-M., Marquelet D., Baufle G.-H., Becque O., Michel-Briand Y., and Pageaut G.Leptospirose grave avec localisation cardiaque.Presse Med.919802579
    203.
    Estavoyer J. M., Racadot E., Couetdic G., Leroy J., and Grosperrin L.Tumor necrosis factor in patients with leptospirosis.Rev. Infect. Dis.13199112451246
    204.
    Evans, M., and G. Baranton. 2000. Leptospirosis outbreak in Eco Challenge 2000 participants, Eurosurveillance Weekly4:000921. [Online.]http://www.eurosurv.org/2000/000921.htm
    205.
    Everard C. O. R., Bennett S., Edwards C. N., Nicholson G. D., Hassell T. A., Carrington D. G., and Everard J. D.An investigation of some risk factors for severe leptospirosis on Barbados.J. Trop. Med. Hyg.9519921332
    206.
    Everard C. O. R., Jones C. J., Inniss V. A., Carrington D. G., and Vaughan A. W.Leptospirosis in dogs on Barbados.Isr. J. Vet. Med.431987288295
    207.
    Everard J. D.Leptospirosis.The Wellcome Trust illustrated history of tropical diseases. The Wellcome Trust, London, U.K.Cox F. E. G.1996111119, 416–418
    208.
    Everard J. D. and Everard C. O. R.Leptospirosis in the Caribbean.Rev. Med. Microbiol.41993114122
    209.
    Faber N. A., Crawford M., LeFebvre R. B., Buyukmihci N. C., Madigan J. E., and Willits N. H.Detection of Leptospira spp. in the aqueous humor of horses with naturally acquired recurrent uveitis.J. Clin. Microbiol.38200027312733
    210.
    Faine S.Guidelines for the control of leptospirosis.1982World Health OrganizationGeneva, Switzerland
    211.
    Faine S.Leptospira and leptospirosis.1994CRC PressBoca Raton, Fla
    212.
    Faine S.LeptospirosisLaboratory diagnosis of infectious diseases: principles and practiceBalows A., Hausler W. J., Ohashi M., and Turano A.11988344352Springer-VerlagNew York, N.Y
    213.
    Faine S., Adler B., Bolin C., and Perolat P.Leptospira and leptospirosis2nd ed.1999MedSciMelbourne, Australia
    214.
    Faine S., Adler B., Christopher W., and Valentine R.Fatal congenital human leptospirosis.Zentbl. Bakteriol.2571984548
    215.
    Faine S., Adler B., and Palit A.Chemical, serological and biological properties of a serotype-specific polysaccharide antigen in Leptospira.Aust. J. Exp. Biol. Med. Sci.521974311319
    216.
    Faine S., Adler B., and Ruta G.A mechanism of immunity to leptospirosis.Aust. J. Exp. Biol. Med. Sci.521974301310
    217.
    Faine S. and Stallman N. D.Amended descriptions of the genus Leptospira Noguchi 1917 and the species L.interrogans (Stimson 1907) Wenyon 1926 and L. biflexa (Wolbach and Binger 1914) Noguchi 1918.Int. J. Syst. Bacteriol.321982461463
    218.
    Fairley N. H.Weil's disease among sewer workers in London.BMJ219341014
    219.
    Famatiga E. G., Topacio T. M., Suva M. H., and Oliveros F. M.Studies on leptospirosis in animals and man in the Philippines. V. Serological survey of leptospirosis among occupationally exposed Filipinos.Southeast Asian J. Trop. Med. Public Health31972482488
    220.
    Feigin R. D. and Anderson D. C.Human leptospirosis.Crit. Rev. Clin. Lab. Sci.51975413467
    221.
    Feigin R. D., Lobes L. A., Anderson D., and Pickering L.Human leptospirosis from immunized dogs.Ann. Intern. Med.791973777785
    222.
    Feresu S. B., Bolin C. A., van de Kemp H., and Korver H.Identification of a serogroup Bataviae Leptospira strain isolated from an ox in Zimbabwe.Zentralbl. Bakteriol.28919991929
    223.
    Feresu S. B., Steigerwalt A. G., and Brenner D. J.DNA relatedness of Leptospira strains isolated from beef cattle in Zimbabwe.Int. J. Syst. Bacteriol.49199911111117
    224.
    Forwell M. A., Redding P. G., Brodie M. J., and Gentleman D. de R.Leptospirosis complicated by fatal intracerebral haemorrhage.BMJ28919841583
    225.
    Fraser D. W., Glosser J. W., Francis D. P., Phillips C. J., Feeley J. C., and Sulzer C. R.Leptospirosis caused by serotype fort-bragg—a suburban outbreak.Ann. Intern. Med.791973786789
    226.
    French J. G. and Holt K. W.FloodsThe public health consequences of disasters.Gregg M. D.19896978Centers for Disease ControlAtlanta, Ga
    227.
    Friedland J. S. and Warrell D. A.The Jarisch-Herxheimer reaction in leptospirosis: possible pathogenesis and review.Rev. Infect. Dis.131991207210
    228.
    Fukunaga M., Horie I., Mifuchi I., and Takemoto M.Cloning, characterization and taxonomic significance of genes for the 5S ribosomal RNA of Leptonema illini strain 3055.J. Gen. Microbiol.137199115231528
    229.
    Fukunaga M., Horie I., Okuzako N., and Mifuchi I.Nucleotide sequence of a 16S rRNA gene for Leptospira interrogans serovar canicola strain Moulton.Nucleic Acids Res.181990366
    230.
    Fukunaga M. and Mifuchi I.The number of large ribosomal RNA genes in Leptospira interrogans and Leptospira biflexa.Microbiol. Immunol.331989459466
    231.
    Fukunaga M. and Mifuchi I.Unique organization of Leptospira interrogans rRNA genes.J. Bacteriol.171198957635767
    232.
    Fuortes L. and Nettleman M.Leptospirosis: a consequence of the Iowa flood.Iowa Med.841994449450
    233.
    Galli M., Esposito R., Crocchiolo P., Chemotti M., Gasparro M., and Dall'Aglio P. P.Immune complexes in leptospirosis.Infection131985156
    234.
    Galton M. M., Powers D. K., Hall A. M., and Cornell R. G.A rapid microscopic-slide screening test for the serodiagnosis of leptospirosis.Am. J. Vet. Res.191958505512
    235.
    Galton M. M., Sulzer C. R., Santa Rosa C. A., and Fields M. J.Application of a microtechnique to the agglutination test for leptospiral antibodies.Appl. Microbiol.1319658185
    236.
    Gauld R. L., Crouch W. L., Kaminsky A. L., Hullinghorst R. L., Gochenour W. S., and Yager R. H.Leptospiral meningitis: report of an outbreak among American troops on Okinawa.JAMA1491952228231
    237.
    Gerritsen M. A., Smits M. A., and Olyhoek T.Random amplified polymorphic DNA fingerprinting for rapid identification of leptospiras of serogroup Sejroe.J. Med. Microbiol.421995336339
    238.
    Giles N., Hathaway S. C., and Stevens A. E.Isolation of Leptospira interrogans serovar hardjo from a viable premature calf.Vet. Rec.1131983174176
    239.
    Gilks C. F., Lambert H. P., Broughton E. S., and Baker C. C.Failure of penicillin prophylaxis in laboratory acquired leptospirosis.Postgrad. Med. J.641988236238
    240.
    Gill N., Waitkins S. A., and Calder I. M.Further update on leptospirosis: continuing risk in fish farmers.BMJ29019851988
    241.
    Gill O. N., Coghlan J. D., and Calder I. M.The risk of leptospirosis in United Kingdom fish farm workers.J. Hyg.9419858186
    242.
    Gillespie R. W. H. and Ryno J.Epidemiology of leptospirosis.Am. J. Public Health531963950955
    243.
    Gochenour W. S., Gleiser C. A., and Ward N. K.Laboratory diagnosis of leptospirosis.Ann. N.Y. Acad. Sci.701958421426
    244.
    Gollop J. H., Katz A. R., Rudoy R. C., and Sasaki D. M.Rat-bite leptospirosis.West. J. Med.15919937677
    245.
    Gonsalez C. R., Casseb J., Monteiro F. G., Paula-Neto J. B., Fernandez R. B., Silva M. B., Camargo E. D., Mairinque J. M., and Tavares L. C.Use of doxycycline for leptospirosis after high-risk exposure in Sao Paulo, Brazil.Rev. Inst. Med. Trop. Sao Paulo4119985961
    246.
    Gordon Smith C. E. and Turner L. H.The effect of pH on the survival of leptospires in water.Bull. WHO2419613543
    247.
    Gravekamp C., van de Kemp H., Carrington D., van Eys G. J. J. M., Everard C. O. R., and Terpstra W. J.Detection of leptospiral DNA by PCR in serum from patients with copenhageni infectionsLeptospirosis. Proceedings of the Leptospirosis Research Conference 1990.Kobayashi Y.1991151164University of Tokyo PressTokyo, Japan
    248.
    Gravekamp C., van de Kemp H., Franzen M., Carrington D., Schoone G. J., van Eys G. J. J. M., Everard C. O. R., Hartskeerl R. A., and Terpstra W. J.Detection of seven species of pathogenic leptospires by PCR using two sets of primers.J. Gen. Microbiol.139199316911700
    249.
    Grégoire N., Higgins R., and Robinson Y.Isolation of leptospires from nephritic kidneys of beef cattle at slaughter.Am. J. Vet. Res.481987370371
    250.
    Grell G., Ho-Ping-Kong H., Ragbeer M. M. S., Barrow O., Ward E. E., and Alleyne G. A. O.Peritoneal dialysis in severe leptospiral renal failure.West Indian Med. J.2019717682
    251.
    Guidugli F., Castro A. A., and Atallah A. N.Antibiotics for preventing leptospirosis (Cochrane Review), Cochrane Library, issue 4.2000Update SoftwareOxford, U.K
    252.
    Guidugli F., Castro A. A., and Atallah A. N.Antibiotics for treating leptospirosis (Cochrane Review), Cochrane Library, Issue 2.2000Update SoftwareOxford, U.K
    253.
    Gussenhoven G. C., van der Hoorn M. A. W. G., Goris M. G. A., Terpstra W. J., Hartskeerl R. A., Mol B. W., van Ingen C. W., and Smits H. L.LEPTO dipstick, a dipstick assay for detection of Leptospira-specific immunoglobulin M antibodies in human sera.J. Clin. Microbiol.3519979297
    254.
    Haake D. A.Spirochaetal lipoproteins and pathogenesis.Microbiology146200014911504
    255.
    Haake D. A., Champion C. I., Martinich C., Shang E. S., Blanco D. R., Miller J. N., and Lovett M. A.Molecular cloning and sequence analysis of the gene encoding OmpL1, a transmembrane outer membrane protein of pathogenic Leptospira spp.J. Bacteriol.175199342254234
    256.
    Haake D. A., Chao G., Zuerner R. L., Barnett J. K., Barnett D., Mazel M., Matsunaga J., Levett P. N., and Bolin C. A.The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection.Infect. Immun.68200022762285
    257.
    Haake D. A., Martinich C., Summers T. A., Shang E. S., Pruetz J. D., McCoy A. M., Mazel M. K., and Bolin C. A.Characterization of leptospiral outer membrane lipoprotein LipL36: downregulation associated with late-log-phase growth and mammalian infection.Infect. Immun.66199815791587
    258.
    Haake D. A., Mazel M. K., McCoy A. M., Milward F., Chao G., Matsunaga J., and Wagar E. A.Leptospiral outer membrane proteins OmpL1 and LipL41 exhibit synergistic immunoprotection.Infect. Immun.67199965726582
    259.
    Haake D. A., Walker E. M., Blanco D. R., Bolin C. A., Miller M. N., and Lovett M. A.Changes in the surface of Leptospira interrogans serovar grippotyphosa during in vitro cultivation.Infect. Immun.59199111311140
    260.
    Haapala D. K., Rogul M., Evans L. B., and Alexander A. D.Deoxyribonucleic acid base composition and homology studies of Leptospira.J. Bacteriol.981969421428
    261.
    Harkin K. R. and Gartrell C. L.Canine leptospirosis in New Jersey and Michigan: 17 cases (1990–1995).J. Am. Anim. Hosp. Assoc.321996495501
    262.
    Harrison N. A. and Fitzgerald W. R.Leptospirosis—can it be a sexually transmitted disease?Postgrad. Med. J.641988163164
    263.
    Hart R. J. C., Gallagher J., and Waitkins S.An outbreak of leptospirosis in cattle and man.BMJ288198419831984
    264.
    Hartman E. G.An IgM- and IgG-specific enzyme-linked immunosorbent assay (ELISA) to detect anti-leptospiral immunoglobulins in dogs.Zentbl. Bakteriol.2571984508510
    265.
    Hartman E. G., Van Houten M., Van der Donk J. A., and Frik J. F.Serodiagnosis of canine leptospirosis by solid-phase enzyme-linked immunosorbent assay.Vet. Immunol. Immunopathol.719843342
    266.
    Hartskeerl R. A. and Terpstra W. J.Leptospirosis in wild animals.Vet. Q.18 (Suppl. 3)1996S149S150
    267.
    Hathaway S. C., Little T. W. A., and Pritchard D. G.Problems associated with the serological diagnosis of Leptospira interrogans serovar hardjo infection in bovine populations.Vet. Rec.11919868486
    268.
    Hathaway S. C., Little T. W. A., and Stevens A. E.Isolation of Leptospira interrogans serovar hardjo from aborted bovine fetuses in England.Vet. Rec.111198258
    269.
    Hathaway S. C., Marshall R. B., Little T. W. A., Headlam S. A., and Winter P. J.Differentiation of reference strains of leptospires of the Pomona serogroup by cross-agglutination absorption and restriction endonuclease analysis.Res. Vet. Sci.391985145150
    270.
    Hathaway S. C., Marshall R. B., Little T. W. A., Headlam S. A., and Winter P. J.Identification by cross-agglutination absorption and restriction endonuclease analysis of leptospires of the Pomona serogroup isolated in the United Kingdom.Res. Vet. Sci.391985151156
    271.
    Haunz E. A. and Cardy J. D.Canicola fever: report of nine cases in one family, with abstract of the world literature.Arch. Intern. Med.891952978993
    272.
    Havens W. P., Bucher C. J., and Reimann H. A.Leptospirosis: a public health hazard. Report of a small outbreak of Weil's disease in bathers.JAMA1161941289291
    273.
    Heath C. W., Alexander A. D., and Galton M. M.Leptospirosis in the United States: 1949–1961.N. Engl. J. Med.2731965857864, 915–922.
    274.
    Hellstrom J. S. and Marshall R. B.Survival of Leptospira interrogans serovar pomona in an acidic soil under simulated New Zealand field conditions.Res. Vet. Sci.2519782933
    275.
    Henry R. A., Johnson R. C., Bohlool B. B., and Schmidt E. L.Detection of Leptospira in soil and water by immunofluorescence staining.Appl. Microbiol.211971953956
    276.
    Hergt R.Meaning of serotype Patoc (biflexa complex) for the diagnosis of leptospirosis by microscopic agglutination test.Zentbl. Bakteriol.2351976506511
    277.
    Hernandez M. S., Aguila J. B., Gonzalez L. P., and Gonzalez V. G.Brote de leptospirosis en niños con predomino meningoencefálico, en el municipio Morón.Rev. Cuba. Med. Trop.431991136139
    278.
    Heron L. G., Reiss-Levy E. A., Jacques T. C., Dickeson D. J., Smythe L. D., and Sorrell T. C.Leptospirosis presenting as a haemorrhagic fever in a traveller from Africa.Med. J. Aust.1671997477479
    279.
    Herrmann J. L.Genomic techniques for identification of Leptospira strains.Pathol. Biol.411993943950
    280.
    Herrmann J. L., Bakoss P., Korver H., Bulu A. A., Bellenger E., Terpstra W. J., Saint Girons I., and Baranton G.A new serovar in the Grippotyphosa serogroup comprising leptospiral isolates from different regions.Int. J. Syst. Bacteriol.441994362364
    281.
    Herrmann J. L., Baril C., Bellenger E., Perolat P., Baranton G., and Saint Girons I.Genome conservation in isolates of Leptospira interrogans.J. Bacteriol.173199175827588
    282.
    Herrmann J. L., Bellenger E., Perolat P., Baranton G., and Saint Girons I.Pulsed-field gel electrophoresis of NotI digests of leptospiral DNA: a new rapid method of serovar identification.J. Clin. Microbiol.30199216961702
    283.
    Hill M. K. and Sanders C. V.Leptospiral pneumonia.Semin. Respir. Infect.1219974449
    284.
    Hodges R. T. and Ekdahl M. O.Use of a fluorescent antibody technique for the serological differentiation of leptospiral serotypes in cultures and in bovine urine.N. Z. Vet. J.211973109115
    285.
    Hoghton M. A. R. and Proce P. A.Leptospirosis hardjo epididymitis.BMJ2921986174
    286.
    Hookey J. V.Characterization of Leptospiraceae by 16S DNA restriction length polymorphisms.J. Gen. Microbiol.139199316811689
    287.
    Hookey J. V.Detection of Leptospiraceae by amplification of 16S ribosomal DNA.FEMS Microbiol. Lett.901992267274
    288.
    Hookey J. V. and Palmer M. F.A comparative investigation and identification of Leptospira interrogans serogroup icterohaemorrhagiae strains by monoclonal antibody and DNA fingerprint analysis.Zentbl. Bakteriol.2751991185199
    289.
    Hübener E. A. and Reiter H.Beiträge zur Aetiologie der Weilschen Krankheit.Dtsch. Med. Wochenschr.41191512751277
    290.
    Hudson C. P., Levett P. N., Edwards C. N., Moosai R., and Roach T. C.Severe primary HIV-1 infection among black persons in Barbados.Int. J. STD AIDS81997393397
    291.
    Humphry T., Sanders S., and Stadius M.Leptospirosis mimicking MLNS.J. Pediatr.911977853854
    292.
    Hyde F. W. and Johnson R. C.Genetic relationship of lyme disease spirochetes to Borrelia, Treponema, and Leptospira spp.J. Clin. Microbiol.201984151154
    293.
    Ido Y., Hoki R., Ito H., and Wani H.The rat as a carrier of Spirochaeta icterohaemorrhagiae, the causative agent of Weil's disease (spirochaetosis icterohaemorrhagica).J. Exp. Med.261917341353
    294.
    Im J.-G., Yeon K. M., Han M. C., Kim C.-W., Webb W. R., Lee J. S., Han Y. C., Chang W. H., and Chi J. G.Leptospirosis of the lung: radiographic findings in 58 patients.Am. J. Roentgenol.1521989955959
    295.
    Imamura S., Matsui H., and Ashizawa Y.Indirect hemagglutination test for detection of leptospiral antibodies.Jpn. J. Exp. Med.441974191197
    296.
    Inada R., Ido Y., Hoki R., Kaneko R., and Ito H.The etiology, mode of infection, and specific therapy of Weil's disease (spirochaetosis icterohaemorrhagica).J. Exp. Med.231916377402
    297.
    International Committee on Systematic Bacteriology Subcommittee on the Taxonomy of LeptospiraMinutes of the meeting, 5 and 6 September 1986, Manchester, England.Int. J. Syst. Bacteriol.371987472473
    298.
    Isogai E., Hirose K., Kimura K., Hayashi S., Kubota T., Fujii N., and Isogai H.Role of platelet-activating-factor (PAF) on cellular responses after stimulation with leptospire lipopolysaccharide.Microbiol. Immunol.411997271275
    299.
    Isogai E., Isogai H., Kubota T., Fujii N., Hayashi S., Indoh T., Takagi S., Miura H., and Kimura K.Apoptosis of lymphocytes in mice administered lipopolysaccharide from Leptospira interrogans.Zentbl. Vetmed. Reihe B451998529537
    300.
    Isogai E., Isogai H., Kurebayashi Y., and Ito N.Biological activities of leptospiral lipopolysaccharide.Zentbl. Bakteriol.26119865364
    301.
    Isogai E., Kitagawa H., Isogai H., Kurebayashi Y., and Ito N.Phagocytosis as a defense mechanism against infection with leptospiras.Zentbl. Bakteriol.26119866574
    302.
    Jackson L. A., Kaufmann A. F., Adams W. G., Phelps M. B., Andreasen C., Langkop C. W., Francis B. J., and Wenger J. D.Outbreak of leptospirosis associated with swimming.Pediatr. Infect. Dis. J.1219934854
    303.
    Jeandel P., Raoult D., Rougier Y., Auger C., and Mailloux M.Late positive blood cultures in leptospiroses (report of four cases).Trans. R. Soc. Trop. Med. Hyg.781984143145
    304.
    Jellison W. L., Stoenner H. G., and Berg G. M.Leptospirosis among Indians in the Dakotas.Rocky Mt. Med. J.5519585658, 121.
    305.
    Jerrett I. V., McOrist S., Waddington J., Browning J. W., Malecki J. C., and McCausland I. P.Diagnostic studies of the fetus, placenta and maternal blood from 265 bovine abortions.Cornell Vet.741984820
    306.
    Jevon T. R., Knudson M. P., Smith P. A., Whitecar P. S., and Blake R. L.A point-source epidemic of leptospirosis: description of cases, cause, and prevention.Postgrad. Med.801986121129
    307.
    Johnson D. W.The Australian leptospiroses.Med. J. Aust.21950724731
    308.
    Johnson D. W., Brown H. E., and Derrick E. H.Weil's disease in Brisbane.Med. J. Aust.11937811818
    309.
    Johnson R. C. and Faine S.LeptospiraBergey's manual of systematic bacteriologyKrieg N. R. and Holt J. G.119846267Williams & WilkinsBaltimore, Md
    310.
    Johnson R. C. and Harris V. G.Differentiation of pathogenic and saprophytic leptospires. 1. Growth at low temperatures.J. Bacteriol.9419672731
    311.
    Johnson R. C. and Rogers P.5-Fluorouracil as a selective agent for growth of leptospirae.J. Bacteriol.871964422426
    312.
    Johnson R. C., Walby J., Henry R. A., and Auran N. E.Cultivation of parasitic leptospires: effect of pyruvate.Appl. Microbiol.261973118119
    313.
    Johnson W. D., Silva I. C., and Rocha H.Serum creatinine phosphokinase in leptospirosis.JAMA2331975981982
    314.
    Johnston J. H., Lloyd J., McDonald J., and Waitkins S.Leptospirosis-an occupational disease of soldiers.J. R. Army Med. Corps1291983111114
    315.
    Jorge R.Une epidemie, a Lisbonne, d'ictere hemorragique d'origine hydrique contracte per os: nosologie, bacteriologie et epidemiologie.Bull. Off. Int. Hyg. Publique24193288117
    316.
    Jost B. H., Adler B., Vinh T., and Faine S.A monoclonal antibody reacting with a determinant on leptospiral lipopolysaccharide protects guinea pigs against leptospirosis.J. Med. Microbiol.221986269275
    317.
    Kalambaheti T., Bulach D. M., Rajakumar K., and Adler B.Genetic organization of the lipopolysaccharide O-antigen biosynthetic locus of Leptospira borgpetersenii serovar Hardjobovis.Microb. Pathog.271999105117
    318.
    Kalsow C. M. and Dwyer A. E.Retinal immunopathology in horses with uveitis.Ocul. Immunol. Inflamm.61998239251
    319.
    Karaseva E. V., Chernukha Y. G., and Piskunova L. A.Results of studying the time of survival of pathogenic leptospira under natural conditions.J. Hyg. Epidemiol. Microbiol. Immunol.171973339345
    320.
    Katz A. R., Manea S. J., and Sasaki D. M.Leptospirosis on Kauai: investigation of a common source waterborne outbreak.Am. J. Public Health81199113101312
    321.
    Katz A. R., Sasaki D. M., Mumm A. H., Escamilla J., Middleton C. R., and Romero S. E.Leptospirosis on Oahu: an outbreak among military personnel associated with recreational exposure.Mil. Med.1621997101104
    322.
    Kaufmann A. F. and Weyant R. S.LeptospiraceaeManual of clinical microbiology6th ed.Murray P. R. et al.1995621625ASM PressWashington, D.C.
    323.
    Kawaoka Y., Naiki M., and Yanagawa R.Radioimmunoassay system using a serovar-specific lipopolysaccharide antigen of Leptospira.J. Clin. Microbiol.101979313316
    324.
    Kee S. H., Kim I. K., Choi M. S., and Chang W. H.Detection of leptospiral DNA by PCR.J. Clin. Microbiol.32199410351039
    325.
    Kelley P. W.LeptospirosisInfectious diseases2nd ed.Gorbach S. L., Bartlett J. G., and Blacklow N. R.199815801587W. B. SaundersPhiladelphia, Pa
    326.
    Kida H., Watanabe H., Yamamoto S., and Yanagawa R.Immunological and morphological analysis of sodium dodecyl sulfate extract of Leptospira.Zentbl. Bakteriol.2361976328335
    327.
    Kim M. J.Serovar identification of Korean leptospiral strains with monoclonal antibodies.Korean J. Intern. Med.321987571578
    328.
    King S. D. and Urquhart A. E.Laboratory investigations on four cases of leptospiral meningitis in Jamaica.West Indian Med. J.241975196201
    329.
    Klarenbeek A. and Schüffner W. A. P.Het voorkomen van een afwijkend leptospira-ras in Nederland.Ned. Tijdschr. Geneeskd.77193342714276
    330.
    Kmety E. and Dikken H.Classification of the species Leptospira interrogans and history of its serovars.1993University Press GroningenGroningen, The Netherlands
    331.
    Knight L. L., Miller N. G., and White R. J.Cytotoxic factor in the blood and plasma of animals during leptospirosis.Infect. Immun.81973401405
    332.
    Ko A. I., Galvao Reis M., Ribeiro Dourado C. M., Johnson W. D., Riley L. W., and the Salvador Leptospirosis Study GroupUrban epidemic of severe leptospirosis in Brazil.Lancet3541999820825
    333.
    Kobayashi Y., Tamai T., and Sada E.Serological analysis of serogroup lcterohaemorrhagiae using monoclonal antibodies.Microbiol. Immunol.29198512291235
    334.
    Korver H., Kolk A. H. J., Vingerhoed J., van Leeuwen J., and Terpstra W. J.Classification of serovars of the lcterohaemorrhagiae serogroup by monoclonal antibodies.Isr. J. Vet. Med.4419881518
    335.
    Kramer K. J., Pang L. W., Minette H. P., and Perrone J. B.Evaluation of the quantitative buffy coat analysis (QBC) system for the detection of leptosira in human blood.Southeast. Asian J. Trop. Med. Public Health251994788789
    336.
    Laing R. W., Teh C., and Toh C. H.Thrombotic thrombocytopenic purpura (TTP) complicating leptospirosis: a previously undescribed phenomenon.J. Clin. Pathol.431990961962
    337.
    Landouzy L. T. J.Fièvre bilieuse ou hépatique.Gaz. Hôpital561883809
    338.
    Landouzy L. T. J.Typhus hépatique.Gaz. Hôpital561883913
    339.
    Law-Koune J. D., Picard P., Van Der Linden T., Michault A., Corbin J. C., and Duval G.Thrombocytopenia in leptospirosis: role of anti-platelet antibodies.Presse Med.17198813151316
    340.
    Lederberg J., Shope R. E., and Oaks S. C.Emerging infections: microbial threats to health in the United States.1992National Academy PressWashington, D.C.
    341.
    Lee M. G., Char G., Dianzumba S., and Prussia P.Cardiac involvement in severe leptospirosis.West Indian Med. J.351986295300
    342.
    Lee R. E. J., Terry S. I., Walker T. M., and Urquhart A. E.The chest radiograph in leptospirosis in Jamaica.Br. J. Radiol.541981939943
    343.
    Lee S. H., Kim K. A., Park Y. G., Seong I. W., Kim M. J., and Lee Y. J.Identification and partial characterization of a novel hemolysin from Leptospira interrogans serovar lai.Gene25420001928
    344.
    LeFebvre R. B.DNA probe for detection of the Leptospira interrogans serovar hardjo genotype hardjo-bovis.J. Clin. Microbiol.25198722362238
    345.
    LeFebvre R. B., Thiermann A. B., and Foley J.Genetic and antigenic differences of serologically indistinguishable leptospires of serovar hardjo.J. Clin. Microbiol.25198720942097
    346.
    Lessa I. and Cortes E.Cerebrovascular accident as a complication of leptospirosis.Lancetii19811113
    347.
    Letocart M., Baranton G., and Perolat P.Rapid identification of pathogenic Leptospira species (Leptospira interrogans, L. borgpetersenii, and L. kirschneri) with species-specific DNA probes produced by arbitrarily primed PCR.J. Clin. Microbiol.351997248253
    348.
    Letocart M., Boerlin P., Boerlin-Petzold F., Goudet J., Baranton G., and Perolat P.Genetic structure of the genus Leptospira by mutlilocus enzyme electrophoresis.Int. J. Syst. Bacteriol.491999231238
    349.
    Levett P. N.Leptospirosis: re-emerging or re-discovered disease?J. Med. Microbiol.481999417418
    350.
    Levett P. N., Branch S. L., and Edwards C. N.Detection of dengue infection in patients investigated for leptospirosis in Barbados.Am. J. Trop. Med. Hyg.622000112114
    350a.
    Levett P. N., Branch S. L., Whittington C. U., Edwards C. N., and Paxton H.Two methods for rapid serological diagnosis of acute leptospirosis.Clin. Diagn. Lab. Immunol.82001349351
    351.
    Levett P. N. and Whittington C. U.Evaluation of the indirect hemagglutination assay for diagnosis of acute leptospirosis.J. Clin. Microbiol.3619981114
    352.
    Levine D. F.Leptospirosis in the milking parlour.Br. J. Hosp. Med.421989340
    353.
    Lin C., Ma T., Ch'en Y. C., and Cheng W.Studies on anicteric leptospirosis. II. Observations on electrocardiograms.Chin. Med. J.841965291298
    354.
    Lin M., Bughio N., and Surujballi O.Expression in Escherichia coli of flaB, the gene coding for a periplasmic flagellin of Leptospira interrogans serovar pomona.J. Med. Microbiol.481999977982
    355.
    Lin M., Surujballi O., Nielsen K., Nadin-Davis S., and Randall G.Identification of a 35-kilodalton serovar-cross-reactive flagellar protein, FlaB, from Leptospira interrogans by N-terminal sequencing, gene cloning, and sequence analysis.Infect. Immun.65199743554359
    356.
    Lindsay S. and Luke I. W.Fatal leptospirosis (Weil's disease) in a newborn infant. Case of intrauterine fetal infection with report of an autopsy.J. Pediatr.3419499094
    357.
    Looke D. F. M.Weil's syndrome in a zoologist.Med. J. Aust.1441986597601
    358.
    Lucchesi P. M. and Parma A. E.A DNA fragment of Leptospira interrogans encodes a protein which shares epitopes with equine cornea.Vet. Immunol. Immunopathol.711999173179
    359.
    Lupidi R., Cinco M., Balanzin D., Delprete E., and Varaldo P. E.Serological follow-up of patients in a localized outbreak of leptospirosis.J. Clin. Microbiol.291991805809
    360.
    Luzzi G. A., Milne L. M., and Waitkins S. A.Rat-bite acquired leptospirosis.J. Infect.1519875760
    361.
    Mackenzie R. B., Reiley C. G., Alexander A. G., Bruckner E. A., Diercks F. H., and Beye H. K.An outbreak of leptospirosis among U.S. army troops in the Canal Zone. I. Clinical and laboratory observations.Am. J. Trop. Med. Hyg.1519665763
    362.
    Mailloux M.Use of the Leptospira biflexa Patoc antigen in the serodiagnosis of leptospirosis.Ann. Inst. Pasteur1121967121125
    363.
    Mailloux M., Dufresne Y., Mazzonelli J., and Dorta de Mazzonelli G. T.Intérêt de la méthode ELISA dans le diagnostic des leptospiroses.Med. Mal. Infect.141984107109
    364.
    Mailloux M., Mazzonelli J., and Dorta de Mazzonelli G. T.Thermoresistant antigen in leptospires. Possibility of a macroscopic diagnosis of leptospirosis with a single antigen.Zentbl. Bakteriol. Mikrobiol. Hyg. A2291974238241
    365.
    Mailloux M., Mazzonelli J. G., and Dufresne Y.Application of an immuno-enzyme technique to titration of antibodies in leptospirosis: ELISA (enzyme-linked immunosorbent assay).Zentbl. Bakteriol.2571984511513
    366.
    Manca N., Verardi R., Colombrita D., Ravizzola G., Savoldi E., and Turano A.Radiometric method for the rapid detection of Leptospira organisms.J. Clin. Microbiol.231986401403
    367.
    Mancel E., Merien F., Pesenti L., Salino D., Angibaud G., and Perolat P.Clinical aspects of ocular leptospirosis in New Caledonia (South Pacific).Aust. N. Z. J. Ophthalmol.271999380386
    368.
    Manev C.Serological characteristics of the leptospira serogroup Pomona. II Changes in the agglutination and absorption properties of the reference strain after formalin- and heat-inactivation.Zentbl. Bakteriol.2361976323327
    369.
    Marı́n-Léon I., Pérez-Lozano M. J., de Villar-Conde E., Dastis-Bendala C., Vargas-Romero J., and Pumarola-Suñé T.Prospective evaluation of the macroagglutination slide test for Leptospira.Serodiagn. Immunother. Infect. Dis.81997191193
    370.
    Marshall R. B., Wilton B. E., and Robinson A. J.Identification of Leptospira serovars by restriction-endonuclease analysis.J. Med. Microbiol.141981163166
    371.
    Marshall R. B., Winter P. J., Thiermann A. B., and Ellis W. A.Genotypes of Leptospira interrogans serovar hardjo in cattle in the UK.Vet. Rec.1171985669670
    372.
    Marshall R. B., Winter P. J., and Yanagawa R.Restriction endonuclease DNA analysis of Leptospira interrogans serovars icterohaemorrhagiae and hebdomadis.J. Clin. Microbiol.201984808810
    373.
    Martin L. and Pettit A.Sero-diagnostic de la spirochaetose icterohaemorrhagique.Bull. Mem. Soc. Med. Hop. Paris421918672675
    374.
    Martinelli R., Luna M. A., and Rocha H.Is rhabdomyolysis an additonal factor in the pathogenesis of acute renal failure in leptospirosis?Rev. Inst. Med. Trop. Sao Paulo361994111114
    375.
    Martı́nez Garcı́a M. A., de Diego Damiá A., Menéndez Villanueva R., and López Hontagas J. L.Pulmonary involvement in leptospirosis.Eur. J. Clin. Microbiol. Infect. Dis.192000471474
    376.
    Martinez Sanchez R., Obregon Fuentes A. M., Perez Sierra A., Baly Gil A., Diaz Gonzalez M., Baro Suarez M., Menendez Capote R., Ruiz Perez A., Sierra Gonzalez G., and Lopez Chavez A. U.The reactogenicity and immunogenicity of the first Cuban vaccine against human leptospirosis.Rev. Cuba. Med. Trop.501998159166
    377.
    Martins M. G., Matos K. T., da Silva M. V., and de Abreu M. T.Ocular manifestations in the acute phase of leptospirosis.Ocul. Immunol. Inflamm.619987579
    378.
    Masri S. A., Nguyen P. T., Gale S. P., Howard C. J., and Jung S. C.A polymerase chain reaction assay for the detection of Leptospira spp. in bovine semen.Can. J. Vet. Res.6119971520
    379.
    Masuzawa T., Nakamura R., Shimizu T., and Yanagihara Y.Biological activities and endotoxic activities of protective antigens (PAgs) of Leptospira interrogans.Zentbl. Bakteriol.2741990109117
    380.
    Matthias M. A.Molecular characterization of pathogenic Leptospira from animals on the island of Barbados. Ph.D. thesis.2000University of the West IndiesBarbados
    381.
    Mazzonelli J., Dorta de Mazzonelli G., and Mailloux M.Possibilité de diagnostique sérologique macroscopique des leptospires à l'aide d'un antigene unique.Med. Mal. Infect.41974253254
    382.
    McClain J. B. L., Ballou W. R., Harrison S. M., and Steinweg D. L.Doxycycline therapy for leptospirosis.Ann. Intern. Med.1001984696698
    383.
    McComb D. E., Smith D. J. W., Coffin D. L., MacCready R. A., and Chang R. S.The use of erythrocyte sensitizing substance in the diagnosis of leptospirosis. I. The sensitized erythrocyte agglutination test.Am. J. Trop. Med. Hyg.6195790100
    384.
    McCrumb F. R., Stockard J. L., Robinson C. R., Turner L. H., Levis D. G., Maisey C. W., Kelleher M. F., Gleiser C. A., and Smadel J. E.Leptospirosis in Malaya. I. Sporadic cases among military and civilian personnel.Am. J. Trop. Med. Hyg.61957238256
    385.
    McGrath H., Adler B., Vinh T., and Faine S.Phagocytosis of virulent and avirulent leptospires by guinea-pig and human polymorphonuclear leukocytes in vitro.Pathology161984243249
    386.
    Merien F., Amouriauz P., Perolat P., Baranton G., and Saint Girons I.Polymerase chain reaction for detection of Leptospira spp. in clinical samples.J. Clin. Microbiol.30199222192224
    387.
    Merien F., Baranton G., and Perolat P.Comparison of polymerase chain reaction with microagglutination test and culture for diagnosis of leptospirosis.J. Infect. Dis.1721995281285
    388.
    Merien F., Baranton G., and Perolat P.Invasion of Vero cells and induction of apoptosis in macrophages by pathogenic Leptospira interrogans are correlated with virulence.Infect. Immun.651997729738
    389.
    Merien F., Perolat P., Mancel E., Persan D., and Baranton G.Detection of leptospiral DNA by polymerase chain reaction in aqueous humor of a patient with unilateral uveitis.J. Infect. Dis.168199313351336
    390.
    Merien F., Truccolo J., Baranton G., and Perolat P.Identification of a 36-kDa fibronectin-binding protein expressed by a virulent variant of Leptospira interrogans serovar icterohaemorrhagiae.FEMS Microbiol. Lett.18520001722
    391.
    Merien F., Truccolo J., Rougier Y., Baranton G., and Perolat P.In vivo apoptosis of hepatocytes in guinea pigs infected with Leptospira interrogans serovar icterohaemorrhagiae.FEMS Microbiol. Lett.169199895102
    392.
    Midwinter A., Vinh T., Faine S., and Adler B.Characterization of an antigenic oligosaccharide from Leptospira interrogans serovar pomona and its role in immunity.Infect. Immun.62199454775482
    393.
    Millar B. D., Chappel R. J., and Adler B.Detection of leptospires in biological fluids using DNA hybridization.Vet. Microbiol.1519877178
    394.
    Miller N. G., Froehling R. C., and White R. J.Activity of leptospires and their products on L cell monolayers.Am. J. Vet. Res.311970371377
    395.
    Milner A. R., Jackson K. B., Woodruff K., and Smart I. J.Enzyme-linked immunosorbent assay for determining specific immunoglobulin M in infections caused by Leptospira interrogans serovar hardjo.J. Clin. Microbiol.221985539542
    396.
    Misao T., Hiroyoshi S., Katsuta K., Nishihara Y., Kobayashi Y., Kuwashima K., and Aso M.Canicola fever in Japan.Am. J. Hyg.631956294307
    397.
    Mitchison M., Bulach D. M., Vinh T., Rajakumar K., Faine S., and Adler B.Identification and characterization of the dTDP-rhamnose biosynthesis and transfer genes of the lipopolysaccharide-related rfb locus in Leptospira interrogans serovar copenhageni.J. Bacteriol.179199712621267
    398.
    Mitchison M., Rood J. I., Faine S., and Adler B.Molecular analysis of a Leptospira borgpetersenii gene encoding an endoflagellar subunit protein.J. Gen. Microbiol.137199115291536
    399.
    Mohammedi I., Chaumentin G., Sab J. M., Dubois J. M., Mignot F., and Robert D.Syndrome de détresse respiratoire aiguë par hémorragie intra-alvéolaire au cours d'une leptospirose.Presse Med.22199311481149
    400.
    Mollaret P. and Ferroir J.Two cases of icterohemorrhagic spirochetosis, one with fatal myocarditis; contribution to the study of meningeal reactions of typical icterogenic forms of spirochetosis.Bull. Mem. Soc. Med. Hop. Paris51193516221632
    401.
    Monno S. and Mizushima Y.Leptospirosis with acute acalculous cholecystitis and pancreatitis.J. Clin. Gastroenterol.1619935254
    402.
    Monsuez J.-J., Kidouche R., Le Gueno B., and Postic D.Leptospirosis presenting as haemorrhagic fever in visitor to Africa.Lancet3491997254255
    403.
    Morgan A. G. and Cawich F.Ascending polyneuropathy in leptospirosis-a case study.Ann. Trop. Med. Parasitol.741980567568
    404.
    Morris J. A. and Hussaini S. N.Characterization of the antibodies detected by the microscopic agglutination test for bovine leptospirosis.J. Hyg.731974425432
    405.
    Mumford C. J.Leptospirosis and water sports.Br. J. Hosp. Med.411989519
    406.
    Murgatroyd F.Chronic meningitis in Weil's disease.BMJ11937711
    407.
    Murgia R., Riquelme N., Baranton G., and Cinco M.Oligonucleotides specific for pathogenic and saprophytic leptospira occurring in water.FEMS Microbiol. Lett.14819972734
    408.
    Muthusethupati M. A. and Shivakumar S.Acute renal failure due to leptospirosis.J. Assoc. Phys. India351987631633
    409.
    Myers D. M.Effect of culture medium on the agglutinability of leptospires by the microscopic agglutination test.Rev. Argent. Microbiol.819761420
    410.
    Myers D. M.Serodiagnosis of human leptospirosis by counterimmunoelectrophoresis.J. Clin. Microbiol.251987897899
    411.
    Myers D. M. and Coltorti E. A.Broadly reacting precipitating and agglutinating antigen of leptospirae.J. Clin. Microbiol.81978580590
    412.
    Myers D. M. and Jelambi F.Isolation and identification of Leptospira hardjo from cattle in Argentina.Trop. Geogr. Med.2719756370
    413.
    Myers D. M. and Varela-Diaz V. M.Selective isolation of leptospiras from contaminated material by incorporation of neomycin to culture media.Appl. Microbiol.251973781786
    414.
    Nelson K. E., Ager E. A., Galton M. M., Gillespie R. W. H., and Sulzer C. R.An outbreak of leptospirosis in Washington State.Am. J. Epidemiol.981973336347
    415.
    Nery L. E., de Paula A. B., Nakatani J., dos Santos M. L., and Ratto O. R.Clinical, radiological and functional pulmonary manifestations in patients with leptospirosis.Rev. Inst. Med. Trop. Sao Paulo191977366373
    416.
    Neves E. d. S., Pereira M. M., Galhardo M. C., Caroli A., Andrade J., Morgado M. G., and Mendes R. P.Leptospirosis patient with AIDS: the first case reported.Rev. Soc. Bras. Med. Trop.2719943942
    417.
    Nicholson G. D., Edwards C. N., Hassell T. A., Everard C. O. R., and Callender J.Urinary diagnostic indices in the management of leptospirosis.West Indian Med. J.3819893338
    418.
    Nicholson V. M. and Prescott J. F.Outer membrane proteins of three pathogenic Leptospira species.Vet. Microbiol.361993123138
    419.
    Nicodemo A. C., Duarte M. I. S., Alves V. A. F., Takakura C. F. H., Santos R. T. M., and Nicodemo E. L.Lung lesions in human leptospirosis: microscopic, immunohistochemical, and ultrastructural features related to thrombocytopenia.Am. J. Trop. Med. Hyg.561997181187
    420.
    Nicolescu M. and Andreescu N.May human leptospirosis develop as a chronic infection?Zentbl. Bakteriol.2571984531534
    421.
    Nie D. K., Wu S. H., Shi M. H., Lu M. L., Jiang S. X., Zhu G. F., Wang H. Q., and Liu Y. M.Studies on endotoxin of Leptospira. I. Extraction of lipopolysaccharides from Leptospira interrogans serovar Lai and analysis of their chemical and biological properties.Chung Kuo I Hsueh Ko Hsueh Yuan Hsueh Pao61984321325
    422.
    O'Brien M. M., Vincent J. M., Person D. A., and Cook B. A.Leptospirosis and acute pancreatitis: a report of ten cases.Pediatr. Infect. Dis. J.171998436438
    423.
    Oie S., Hironaga K., Koshiro A., Konishi H., and Yoshii Z.In vitro susceptibilities of five Leptospira strains to 16 antimicrobial agents.Antimicrob. Agents Chemother.241983905908
    424.
    Oliveira M. A. A., Caballero O. L., Dias Neto E., Koury M. C., Romanha A. J., Carvalho J., Hartskeerl R. A., and Simpson A. J. G.Use of nondenaturing silver-stained polyacrylamide gel analysis of polymerase chain reaction amplification products for the differential diagnosis of Leptospira interrogans infection.Diagn. Microbiol. Infect. Dis.221995343348
    425.
    Oliveira V. J. C., Rocha J. M. B., Silva G. B., and Cabral C. L. N.Observations on a new epidemic outbreak of leptospirosis in greater Recife, Brazil, in 1975.Rev. Inst. Adolfo Lutz3719773336
    426.
    O'Neill K. M., Rickman L. S., and Lazarus A. A.Pulmonary manifestations of leptospirosis.Rev. Infect. Dis.131991705709
    427.
    Orr H. S. and Little T. W. A.Isolation of leptospira of the serotype hardjo from bovine kidneys.Res. Vet. Sci.271979343346
    428.
    Pacciarini M. L., Savio M. L., Donini G., and Tagliabue S.The search for improved methods for diagnosing leptospirosis: the approach of a laboratory in Brescia, Italy.Rev. Sci. Tech.121993647663
    429.
    Pacciarini M. L., Savio M. L., Tagliabue S., and Rossi C.Repetitive sequences cloned from Leptospira interrogans serovar hardjo genotype hardjoprajitno and their application to serovar identification.J. Clin. Microbiol.30199212431249
    430.
    Padre L. P., Watt G., Tuazon M. L., Gray M. R., and Laughlin L. W.A serologic survey of rice-field leptospirosis in central Luzon, Philippines.Southeast Asian J. Trop. Med. Public Health191988197199
    431.
    Palit A. and Gulasekharam J.Genus-specific leptospiral antigen and its possible use in laboratory diagnosis.J. Clin. Pathol.261973716
    432.
    Palit A., Haylock L. M., and Cox J. C.Storage of pathogenic leptospires in liquid nitrogen.J. Appl. Bacteriol.611986407411
    433.
    Palmer M. and Hookey J.The chemiluminescent detection of leptospiral antigen.Zentbl. Bakteriol.2771992300308
    434.
    Palmer M., Waitkins S. A., and Zochowski W.Survival of leptospires in commercial blood culture systems.Zentbl. Bakteriol. Mikrobiol. Hyg. A2571984480487
    435.
    Palmer M. F., Waitkins S. A., and Wanyangu S. W.A comparison of live and formalised leptospiral microscopic agglutination test.Zentbl. Bakteriol.2651987151159
    436.
    Pan American Health OrganizationImpact of Hurricane Mitch on Central America.Epidemiol. Bull.191998113
    437.
    Panidis D., Rousso D., Skiadopoulos S., Vavilis D., and Kalogeropoulos A.Hypothalamic-pituitary deficiency after Weil's syndrome: a case report.Fertil. Steril.62199410771079
    438.
    Pappas M. G., Ballou R., Gray M. R., Takafuji E. T., Miller R. N., and Hockmeyer W. T.Rapid serodiagnosis of leptospirosis using the IgM-specific dot-ELISA: comparison with the microscopic agglutination test.Am. J. Trop. Med. Hyg.341985346354
    439.
    Parenti D. M., Steinberg W., and Kang P.Infectious causes of acute pancreatitis.Pancreas131996256371
    440.
    Park K.-H., Chang W.-H., Lee J.-S., Choi K.-W., Park K.-H., and Oh H.-B.Diagnosis of leptospirosis by enzyme-linked immunosorbent assay.J. Korea Soc. Microbiol.211986181189
    441.
    Park S. H., Ahn B. Y., and Kim M. J.Expression and immunologic characterization of recombinant heat shock protein 58 of Leptospira species: a major target antigen of the humoral immune response.DNA Cell. Biol.181999903910
    442.
    Park S.-K., Lee S.-H., Rhee Y.-K., Kang S.-K., Kim K.-J., Kim M.-C., Kim K.-W., and Chang W.-H.Leptospirosis in Chonbuk province of Korea in 1987: a study of 93 patients.Am. J. Trop. Med. Hyg.411989345351
    443.
    Parma A. E., Fernandez A. S., Santisteban C. G., Bowden R. A., and Cerone S. I.Tears and aqueous humor from horses inoculated with Leptospira contain antibodies which bind to cornea.Vet. Immunol. Immunopathol.141987181185
    444.
    Parma A. E., Seijo A., Lucchesi P. M., Deodato B., and Sanz M. E.Differentiation of pathogenic and non-pathogenic leptospires by means of the polymerase chain reaction.Rev. Inst. Med. Trop. Sao Paulo391997203207
    445.
    Parsons M.Electrocardiographic changes in leptospirosis.BMJ21965201203
    446.
    Paster B. J., Dewhirst F. E., Weisburg W. G., Tordoff L. A., Fraser G. J., Hespell R. B., Stanton T. B., Zablen L., Mandelco L., and Woese C. R.Phylogenetic analysis of the spirochetes.J. Bacteriol.173199161016109
    447.
    Penna D., de Brito T., Pupo A. A., Machado M. M., Galvão P. A. A., and Soares de Almeida S.Kidney biopsy in human leptospirosis.Am. J. Trop. Med. Hyg.121963896901
    448.
    Pereira M. M., Andrade J., Marchevsky R. S., and Ribeiro dos Santos R.Morphological characterization of lung and kidney lesions in C3H/HeJ mice infected with Leptospira interrogans serovar icterohaemorrhagiae: defect of a CD4+ and CD8+ T-cells are prognosticators of the disease progression.Exp. Toxicol. Pathol.501998191198
    449.
    Pereira M. M., Matsuo M. G., Bauab A. R., Vasconcelos S. A., Moraes Z. M., Baranton G., and Saint Girons I.A clonal subpopulation of Leptospira interrogans sensu stricto is the major cause of leptospirosis outbreaks in Brazil.J. Clin. Microbiol.382000450452
    450.
    Pérolat P., Chappel R. J., Adler B., Baranton G., Bulach D. M., Billinghurst M. L., Letocart M., Merien F., and Serrano M. S.Leptospira fainei sp. nov., isolated from pigs in Australia.Int. J. Syst. Bacteriol.481998851858
    451.
    Pérolat P., Grimont F., Regnault B., Grimont P. A. D., Fournié E., Thevenet H., and Baranton G.rRNA gene restriction patterns of Leptospira: a molecular typing system.Res. Microbiol.1411990159171
    452.
    Pérolat P., Lecuyer I., Postic D., and Baranton G.Diversity of ribosomal DNA fingerprints of Leptospira serovars provides a database for subtyping and species assignation.Res. Microbiol.1441993515
    453.
    Pérolat P., Merien F., Ellis W. A., and Baranton G.Characterization of Leptospira isolates from serovar hardjo by ribotyping, arbitrarily primed PCR, and mapped restriction site polymorphisms.J. Clin. Microbiol.32199419491957
    454.
    Perrocheau A. and Pérolat P.Epidemiology of leptospirosis in New Caledonia (South Pacific): a one-year study.Eur. J. Epidemiol.131997161167
    455.
    Petchclai B., Hiranras S., and Potha U.Gold immunoblot analysis of IgM-specific antibody in the diagnosis of human leptospirosis.Am. J. Trop. Med. Hyg.451991672675
    456.
    Peter G.Leptospirosis: a zoonosis of protean manifestations.Pediatr. Infect. Dis. J.11982282288
    457.
    Petzetakis M.A propos d'une épidémie de spirochétose ictérohémmorragique à l'ile de Syra: origine hydrique del'épidémie, presence des spirochètes chez les rats d'égout, en Grèce.Bull. Soc. Pathol. Exot.251932411416
    458.
    Phillip N. A.Leptospirosis: New Zealand's no. 1 dairy occupational disease.N. Z. Vet. J.24197668
    459.
    Pierce P. F., Utz J. P., and Lack E. E.LeptospirosisPathology of infectious diseasesConnor D. H., Chandler F. W., Schwartz D. A., Manz H. J., and Lack E. E.11997615619Appleton & LangeStamford, Conn
    460.
    Pike R. M.Laboratory-associated infections: summary and analysis of 3921 cases.Health Lab. Sci.131976105114
    461.
    Poh S. C. and Soh C. S.Lung manifestations in leptospirosis.Thorax251970751755
    462.
    Postic D., Riquelme-Sertour N., Merien F., Pérolat P., and Baranton G.Interest of partial 16S rDNA gene sequences to resolve heterogeneities between Leptospira collections: application to L. meyeri.Res. Microbiol.1512000333341
    463.
    Pot A. W. and Dornickx C. G. T.The complement fixation test in the diagnosis of Weil's disease.J. Pathol. Bacteriol.431936367372
    464.
    Prescott J. F., Ferrier R. L., Nicholson V. M., Johnston K. M., and Hoff B.Is canine leptospirosis underdiagnosed in southern Ontario? A case report and serological survey.Can. Vet. J.321991481486
    465.
    Prescott J. F., Miller R. B., and Nicholson V. M.Isolation of Leptospira hardjo from kidneys of Ontario cattle at slaughter.Can. J. Vet. Res.511987229231
    466.
    Prescott J. F., Miller R. B., Nicholson V. M., Martin S. W., and Lesnick T.Seroprevalence and association with abortion of leptospirosis in cattle in Ontario.Can. J. Vet. Res.521988210215
    467.
    Rajiv C., Manjuran R. J., Sudhayakumar N., and Haneef M.Cardiovascular involvement in leptospirosis.Indian Heart J.481996691694
    468.
    Ralph D. and McClelland M.Phylogenetic evidence for horizontal transfer of an intervening sequence between species in a spirochete genus.J. Bacteriol.176199459825987
    469.
    Ralph D., McClelland M., Welsh J., Baranton G., and Perolat P.Leptospira species categorized by arbitrarily primed polymerase chain reaction (PCR) and by mapped restriction polymorphisms in PCR-amplified rRNA genes.J. Bacteriol.1751993973981
    470.
    Ram P. and Chandra M. S.Unusual electrocardiographic abnormality in leptospirosis: case reports.J. Vasc. Dis.361985477482
    471.
    Ramachandran S.Electrocardiographic abnormalities in leptospirosis.J. Trop. Med. Hyg.781975210213
    472.
    Ramachandran S. and Perera M. V. F.Cardiac and pulmonary involvement in leptospirosis.Trans. R. Soc. Trop. Med. Hyg.7119775659
    473.
    Ramachandran S., Rajapakse C. N. A., Perera M. V. F., and Yoganathan M.Patterns of acute renal failure in leptospirosis.J. Trop. Med. Hyg.791976158160
    474.
    Ramadass P., Jarvis B. D. W., Corner R. J., Cinco M., and Marshall R. B.DNA relatedness among strains of Leptospira biflexa.Int. J. Syst. Bacteriol.401990231235
    475.
    Ramadass P., Jarvis B. D. W., Corner R. J., Penny D., and Marshall R. B.Genetic characterization of pathogenic Leptospira species by DNA hybridization.Int. J. Syst. Bacteriol.421992215219
    476.
    Ramos-Morales F., Dı́az-Rivera R. S., Cintrón-Rivera A. A., Rullán J. A., Benenson A. S., and Acosta-Matienzo J.The pathogenesis of leptospiral jaundice.Ann. Intern. Med.511959861878
    477.
    Rathinam S. R., Rathnam S., Selvaraj S., Dean D., Nozik R. A., and Namperumalsamy P.Uveitis associated with an epidemic outbreak of leptospirosis.Am. J. Ophthalmol.12419977179
    478.
    Rathinam S., Ratnam S., Sureshbabu L., and Natarajaseenivasan K.Leptospiral antibodies in patients with recurrent ophthalmic involvement.Indian J. Med. Res.10319966668
    479.
    Ratnam S.Leptospirosis: an Indian perspective.Indian J. Med. Microbiol.121994228239
    480.
    Ratnam S., Sundararaj T., Subramanian S., Madanagopalan N., and Jayanthi V.Humoral and cell-mediated immune responses to leptospires in different human cases.Trans. R. Soc. Trop. Med. Hyg.781984539542
    481.
    Redstone J. S. and Woodward M. J.The development of a ligase mediated PCR with potential for differentiation of serovars within Leptospira interrogans.Vet. Microbiol.511996351362
    482.
    Reisberg B. E., Wurtz R., Diaz P., Francis B., Zakowski P., Fannin S., Sesline D., Waterman S., Sanderson R., McChesney T., Boddie R., Levy M., Miller G., and Herrera G.Outbreak of leptospirosis among white-water rafters— Costa Rica, 1996.Morb. Mortal. Wkly. Rep.461997577579
    483.
    Renesto P., Lorvellec-Guillon K., Drancourt M., and Raoult D.rpoB gene analysis as a novel strategy for identification of spirochetes from the genera Borrelia, Treponema, and Leptospira.J. Clin. Microbiol.38200022002203
    484.
    Ribeiro M. A., Assis C. S. N., and Romero E. C.Serodiagnosis of human leptospirosis employing immunodominant antigen.Serodiagn. Immunother. Infect. Dis.61994140144
    485.
    Ribeiro M. A., Souza C. C., and Almeida S. H. P.Dot-ELISA for human leptospirosis employing immunodominant antigen.J. Trop. Med. Hyg.981995452456
    486.
    Richaud C., Margarita D., Baranton G., and Saint Girons I.Cloning of genes required for amino acid biosynthesis from Leptospira interrogans serovar icterohaemorrhagiae.J. Gen. Microbiol.1361990651656
    487.
    Rittenberg M. B., Linscott W. D., and Ball M. G.Simple method for separating leptospirae from contaminating microorganisms.J. Bacteriol.761958669670
    488.
    Robertson A. and Boulanger P.Comparison of the complement-fixation test and the microscopic agglutination test (agglutination-lysis) for the detection of leptospiral serogroup antibodies.Can. J. Comp. Med.271963113120
    489.
    Robertson M. H., Clarke I. R., Coghlan J. D., and Gill O. N.Leptospirosis in trout farmers.Lancetii1981626627
    490.
    Robinson A. J., Ramadass P., Lee A., and Marshall R. B.Differentiation of subtypes within Leptospira interrogans serovars hardjo, balcanica and tarassovi, by bacterial restriction-endonuclease DNA analysis (BRENDA).J. Med. Microbiol.151982331338
    491.
    Roch P., Srámková L., and Salák J.The agglutinating and immunofluorescent activities of antileptospiral antibodies of human sera and of immunoglobulins M and G.J. Hyg. Epidemiol. Microbiol. Immunol.201976341352
    492.
    Romero E. C., Billerbeck A. E. C., Lando V. S., Camargo E. D., Souza C. C., and Yasuda P. H.Detection of Leptospira DNA in patients with aseptic meningitis by PCR.J. Clin. Microbiol.36199814531455
    493.
    Romero E. C., Caly C. R., and Yasuda P. H.The persistence of leptospiral agglutinins titers in human sera diagnosed by the microscopic agglutination test.Rev. Inst. Med. Trop. Sao Paulo401998183184
    494.
    Roth E. E., Linder D., and Adams W. V.The use of agar plates as an aid for the isolation of leptospires.Am. J. Vet. Res.221961308312
    495.
    Rugman F. P., Pinn G., Palmer M. F., Waite M., and Hay C. R.Anticardiolipin antibodies in leptospirosis.J. Clin. Pathol.441991517519
    496.
    Rule P. L. and Alexander A. D.Gellan gum as a substitute for agar in leptospiral media.J. Clin. Microbiol.231986500504
    497.
    Russell R. W. R.Treatment of leptospirosis with oxytetracycline.Lancetii195811431145
    498.
    Saint Girons I., Bourhy P., Ottone C., Picardeau M., Yelton D., Hendrix R. W., Glaser P., and Charon N.The LE1 bacteriophage replicates as a plasmid within Leptospira biflexa: construction of an L. biflexa-Escherichia coli shuttle vector.J. Bacteriol.182200057005705
    499.
    Sakamoto N., Yanagawa R., Ono E., Kida H., Mori M., Arimitsu Y., Akama K., Yasuda J., and Too K.Detection of antibodies to leptospiral genus-specific antigen in human and animal sera by indirect hemagglutination test with a partially purified genus-specific protein antigen.Zentbl. Bakteriol.2591985548556
    500.
    Sakula A. and Moore W.Benign leptospirosis: first reported outbreak in the British Isles due to strains belonging to the Hebdomadis serogroup of Leptospira interrogans.BMJi1969226228
    501.
    Sanders E. J., Rigau-Perez J. G., Smits H. L., Deseda C. C., Vorndam V. A., Aye T., Spiegel R. A., Weyant R. S., and Bragg S. L.Increase of leptospirosis in dengue-negative patients after a hurricane in Puerto Rico in 1996.Am. J. Trop. Med. Hyg.611999399404
    502.
    Savio M. L., Rossi C., Fusi P., Tagliabue S., and Pacciarini M. L.Detection and identification of Leptospira interrogans serovars by PCR coupled with restriction endonuclease analysis of amplified DNA.J. Clin. Microbiol.321994935941
    503.
    Schaeffer M.Leptospiral meningitis. Investigation of a water-borne epidemic due to L. pomona.J. Clin. Investig.301951670671
    504.
    Schönberg A.Growth of 10 Leptospira interrogans serovars using polyvinylpyrrolidone(PVP)-treated Tween in protein-free medium.Zentbl. Bakteriol. Mikrobiol. Hyg. A2541983540544
    505.
    Schoone G. J., Everard C. O. R., Korver H., Carrington D. G., Inniss V. A., and Terpstra W. J.An immunoprotective monoclonal antibody directed against Leptospira interrogans serovar copenhageni.J. Gen. Microbiol.13519897378
    506.
    Schüffner W. and Mochtar A.Versuche sur Aufteilung von Leptospirenstämmen, mit einleitenden Bemerkungen über den Verlauf von Agglutination und Lysis.Zentbl. Bakteriol.1011927405413
    507.
    Schwartz D. A.Emerging and reemerging infections: progress and challenges in the subspecialty of infectious disease pathology.Arch. Pathol. Lab. Med.1211997776784
    508.
    Segers R. P. A. M., van der Drift A., de Njis A., Corcione P., van der Zeijst B. A. M., and Gaastra W.Molecular analysis of a sphingomyelinase C gene from Leptospira interrogans serovar hardjo.Infect. Immun.58199021772185
    509.
    Segers R. P. A. M., van Gestel J. A., van Eys G. J. J. M., van der Zeijst B. A. M., and Gaastra W.Presence of putative sphingomyelinase genes among members of the family Leptospiraceae.Infect. Immun.60199217071710
    510.
    Sehgal S. C., Murhekar M. V., and Sugunan A. P.Outbreak of leptospirosis with pulmonary involvement in North Andaman.Indian J. Med. Res.1021995912
    511.
    Sehgal S. C., Sugunan A. P., Murhekar M. V., Sharma S., and Vijayachari P.Randomized controlled trial of doxycycline prophylaxis against leptospirosis in an endemic area.Int. J. Antimicrob. Agents132000249255
    512.
    Sehgal S. C., Vijayachari P., Sharma S., and Sugunana A. P.LEPTO dipstick: a rapid and simple method for serodiagnosis of acute leptospirosis.Trans. R. Soc. Trop. Med. Hyg.931999161164
    513.
    Sehgal S. C., Vijayachari P., and Subramaniam V.Evaluation of leptospira micro capsule agglutination test (MCAT) for serodiagnosis of leptospirosis.Indian J. Med. Res.1061997504507
    514.
    Seki M., Sato T., Aritmitsu Y., Matuhasi T., and Kobayashi S.One-point method for serological diagnosis of leptospirosis: a microcapsule agglutination test.Epidemiol. Infect.991987399405
    515.
    Shang E. S., Summers T. A., and Haake D. A.Molecular cloning and sequence analysis of the gene encoding LipL41, a surface-exposed lipoprotein of pathogenic Leptospira species.Infect. Immun.64199623222330
    516.
    Sharma O. P., Eltahir N., and Roy M.Facial palsy in a patient with leptospirosis: causal or accidental.Sarcoidosis Vasc. Diffuse Lung Dis.161999104106
    517.
    Shaw R. D.Kayaking as a risk factor for leptospirosis.Mo. Med.891992354357
    518.
    Shenberg E.Growth of pathogenic Leptospira in chemically defined media.J. Bacteriol.93196715981606
    519.
    Shimizu T., Matsusaka E., Takayanagi K., masuzawa T., Iwamoto Y., Morita T., Mifuchi I., and Yanagihara Y.Biological activities of lipopolysaccharide-like substance (LLS) extracted from Leptospira interrogans serovar canicola strain Moulton.Microbiol. Immunol.311987727735
    520.
    Shinozaki F., Sada E., Tamai T., and Kobayashi Y.Characterization of Leptospira strains HY-1, HY-2, and HY-10 isolated in Korea by means of monoclonal antibodies and restriction endonuclease analysis.Am. J. Trop. Med. Hyg.461992342349
    521.
    Shpilberg O., Shaked Y., Maier M. K., Samra D., and Samra Y.Long-term follow-up after leptospirosis.South. Med. J.831990405407
    522.
    Silva M. V., Camargo E. D., Batista L., Vaz A. J., Ferreira A. W., and Barbosa P. R. S.Application of anti-leptospira ELISA-IgM for the etiologic elucidation of meningitis.Rev. Inst. Med. Trop. Sao Paulo381996153156
    523.
    Silva M. V., Nakamura P. M., Camargo E. D., Batista L., Vaz A. J., Brandão A. P., and Ferreira A. W.Dot-ELISA-IgM in saliva for the diagnosis of human leptospirosis using polyester fabric-resin as support.Rev. Inst. Med. Trop. Sao Paulo361994475478
    524.
    Silva M. V., Nakamura P. M., Camargo E. D., Batista L., Vaz A. J., Romero E. C., and Brandão A. P.Immunodiagnosis of human leptospirosis by dot-ELISA for the detection of IgM, IgG, and IgA antibodies.Am. J. Trop. Med. Hyg.561997650655
    525.
    Silverstein C. M.Pulmonary manifestations of leptospirosis.Radiology611953327334
    526.
    Simões J., Azevedo J. F. d., and Palmeiro J. M.Some aspects of the Weil's disease epidemiology based on a recent epidemic after a flood in Lisbon (1967).An. Esc. Nac. Saude Publica Med. Trop.319691932
    527.
    Simpson F. G., Green K. A., Haug G. J., and Brookes D. L.Leptospirosis associated with severe pulmonary haemorrhage in Far North Queensland.Med. J. Aust.1691998151153
    528.
    Skilbeck N. W. and Miller G. T.A serological survey of leptospirosis in Gippsland dairy farmers.Med. J. Aust.1441986565567
    529.
    Slee K. J., McOrist S., and Skilbeck N. W.Bovine abortion associated with Leptospira interrogans serovar hardjo infection.Aust. Vet. J.601983204206
    530.
    Smibert R. M.The SpirochaetalesCRC handbook of microbiology2nd edLaskin A. I. and Lechavelier H. A.11977195228CRC PressCleveland, Ohio
    531.
    Smith D. J. W. and Self H. R. M.Observations on the survival of Leptospira australis A in soil and water.J. Hyg.531955436444
    532.
    Smith J.Weil's disease in the north-east of Scotland.Br. J. Ind. Med.61949213220
    533.
    Smits H. L., Ananyina Y. V., Chereshsky A., Dancel L., Lai A. F. R. F., Chee H. D., Levett P. N., Masuzawa T., Yanagihara Y., Muthusethupathi M. A., Sanders E. J., Sasaki D. M., Domen H., Yersin C., Aye T., Bragg S. L., Gussenhoven G. C., Goris M. G., Terpstra W. J., and Hartskeerl R. A.International multicenter evaluation of the clinical utility of a dipstick assay for detection of Leptospira-specific immunoglobulin M antibodies in human serum specimens.J. Clin. Microbiol.37199929042909
    534.
    Smits H. L., van Der Hoorn M. A., Goris M. G., Gussenhoven G. C., Yersin C., Sasaki D. M., Terpstra W. J., and Hartskeerl R. A.Simple latex agglutination assay for rapid serodiagnosis of human leptospirosis.J. Clin. Microbiol.38200012721275
    535.
    Smythe L., Dohnt M., Symonds M., Barnett L., Moore M., Brookes D., and Vallanjon M.Review of leptospirosis notifications in Queensland and Australia: January 1998–June 1999.Commun. Dis. Intell.242000153157
    536.
    Sodeman W. A. and Killough J. H.The cardiac manifestations of Weil's disease.Am. J. Trop. Med. Hyg.311951479488
    537.
    Solbrig M. V., Sher J. H., and Kula R. W.Rhabdomyolysis in leptospirosis (Weil's disease).J. Infect. Dis.1561987692693
    538.
    Sonrier C., Branger C., Michel V., Ruvoën-Clouet N., Ganière J. P., and André-Fontaine G.Evidence of cross-protection within Leptospira interrogans in an experimental model.Vaccine1920008694
    539.
    Stamm L. V. and Charon N. W.Plate assay for detection of Leptospira interrogans serovar pomona hemolysin.J. Clin. Microbiol.101979590592
    540.
    Stamm L. V., Parrish E. A., and Gherardini F. C.Cloning of the recA gene from a free-living leptospire and distribution of RecA-like protein among spirochetes.Appl. Environ. Microbiol.571991183189
    541.
    Staneck J. L., Henneberry R. C., and Cox C. D.Growth requirements of pathogenic Leptospira.Infect. Immun.71973886897
    542.
    Stimson A. M.Note on an organism found in yellow-fever tissue.Public Health Rep.221907541
    542a.
    St. John M. A., King S., Bullen S. E. M., Cherian J., and Levett P. N.Leptospirosis occurring in two children after fresh water immersion.West Indian Med. J.492000340343
    543.
    Stokes A., Ryle J. A., and Tytler W. H.Weil's disease (Spirochaetosis lctero-haemorrhagica) in the British army in Flanders.Lanceti1917142153
    544.
    Stolze E., Schaad J. D. G., and Bool P. H.Weil's disease associated with pancreatic necrosis.Trop. Geogr. Med.1119599395
    545.
    Stuart R. D.Weil's disease in Glasgow sewer workers.BMJi1939324326
    546.
    Sulzer C. R., Glosser J. W., Rogers F., Jones W. L., and Frix M.Evaluation of an indirect hemagglutination test for the diagnosis of human leptospirosis.J. Clin. Microbiol.21975218221
    547.
    Sulzer C. R. and Jones W. L.Evaluation of a hemagglutination test for human leptospirosis.Appl. Microbiol.261973655657
    548.
    Sulzer C. R. and Jones W. L.Leptospirosis: methods in laboratory diagnosis. U.S.1978Department of Health, Education and WelfareAtlanta, Ga
    549.
    Sulzer C. R. and Jones W. L.A modified semi-micro method for the test for leptospirosis.Health Lab. Sci.1019731317
    550.
    Swain R. H. A.The electron-microscopical anatomy of Leptospira canicola.J. Pathol. Bacteriol.731957155158
    551.
    Takafuji E. T., Kirkpatrick J. W., Miller R. N., Karwacki J. J., Kelley P. W., Gray M. R., McNeill K. M., Timboe H. L., Kane R. E., and Sanchez J. L.An efficacy trial of doxycycline chemoprophylaxis against leptospirosis.N. Engl. J. Med.3101984497500
    552.
    Takahashi Y., Akase K., Hirano H., and Fukunaga M.Physical and genetic maps of the Leptospira interrogans serovar icterohaemorrhagiae strain Ictero no. 1 chromosome and sequencing of a 19-kb region of the genome containing the 5S rRNA gene.Gene21519983745
    553.
    Takahashi Y., Kishida M., Yamamoto S., and Fukunaga M.Repetitive sequence of Leptospira interrogans serovar icterohaemorrhagiae strain Ictero No. 1: a sensitive probe for demonstration of Leptospira interrogans strains.Microbiol. Immunol.431999669678
    554.
    Takashima I., Ngoma M., and Hashimoto N.Antimicrobial effects of a new carboxyquinolone drug, Q-35, on five serogroups of Leptospira interroagns.Antimicrob. Agents Chemother.371993901902
    555.
    Tamai T., Sada E., and Kobayashi Y.Restriction endonuclease DNA analysis of Leptospira interrogans serovars Icterohaemorrhagiae and Copenhageni.Microbiol. Immunol.321988887894
    556.
    Tan D. S. K., Suleiman A. B., and Jeyaindran S.16 cases of acute renal failure due to leptospirosis.Med. J. Malaysia411986152155
    557.
    Tan D. S. K. and Welch Q. B.Evaluation of Leptospira biflexa antigens for screening human sera by the microscopic agglutination (MA) test in comparison with the sensitized-erythrocyte-lysis (SEL) test.Southeast Asian J. Trop. Med. Public Health519741216
    558.
    Taylor K. A., Barbour A. G., and Thomas D. D.Pulsed-field gel electrophoretic analysis of leptospiral DNA.Infect. Immun.591991323329
    559.
    Taylor M. J., Ellis W. A., Montgomery J. M., Yan K. T., McDowell S. W., and Mackie D. P.Magnetic immuno capture PCR assay (MIPA): detection of Leptopsira borgpetersenii serovar hardjo.Vet. Microbiol.561997135145
    560.
    Teglia O. F., Battagliotti C., Villavicencio R. L., and Cunha B. A.Leptospiral pneumonia.Chest1081995874875
    561.
    Terpstra W. J.Typing leptospira from the perspective of a reference laboratory.Acta Leidensia6019927987
    562.
    Terpstra W. J., Jabboury-Postema J., and Korver H.Immunoperoxidase staining of leptospires in blood and urine.Zentbl. Bakteriol.2541983534539
    563.
    Terpstra W. J., Korver H., Schoone G. J., van Leeuwen J., Schönemann C. E., De Jonge-Aglibut M., and Kolk A. H. J.Comparative classification of Leptospira serovars of the Pomona serogroup by monolconal antibodies and restriction-endonuclease analysis.Zentbl. Bakteriol.2661987412421
    564.
    Terpstra W. J., Korver H., Van Leeuwen J., Klatser P. R., and Kolk A. H. J.The classification of Sejroe group serovars of Leptospira interrogans with monoclonal antibodies.Zentbl. Bakteriol.2591985498506
    565.
    Terpstra W. J., Ligthart G. S., and Schoone G. J.ELISA for the detection of specific IgM and IgG in human leptospirosis.J. Gen. Microbiol.1311985377385
    566.
    Terpstra W. J., Ligthart G. S., and Schoone G. J.Serodiagnosis of human leptospirosis by enzyme-linked-immunosorbent-assay (ELISA).Zentbl. Bakteriol.2471980400405
    567.
    Terpstra W. J., Schoone G. J., and Ligthart G. S.Counterimmunoelectrophoresis in the diagnosis of human leptospirosis.Zentbl. Bakteriol.2441979285290
    568.
    Terpstra W. J., Schoone G. J., Ligthart G. S., and ter Schegget J.Detection of Leptospira interrogans in clinical specimens by in situ hybridization using biotin-labelled DNA probes.J. Gen. Microbiol.1331987911914
    569.
    Terpstra W. J., Schoone G. J., and ter Schegget J.Detection of leptospiral DNA by nucleic acid hybridization with 32P- and biotin-labelled probes.J. Med. Microbiol.2219862328
    570.
    Terry J., Trent M., and Bartlett M.A cluster of leptospirosis among abattoir workers.Commun. Dis. Intell.242000158160
    571.
    Thiermann A. B.Bovine leptospirosis: bacteriologic versus serologic diagnosis of cows at slaughter.Am. J. Vet. Res.44198322442245
    572.
    Thiermann A. B.Use of solid medium for isolation of leptospires of the hebdomadis serogroup from bovine milk and urine.Am. J. Vet. Res.42198121432145
    573.
    Thiermann A. B. and Garrett L. A.Enzyme-linked immunosorbent assay for the detection of antibodies to Leptospira interrogans serovars hardjo and pomona in cattle.Am. J. Vet. Res.441983884887
    574.
    Thiermann A. B., Handsaker A. L., Foley J. W., White F. W., and Kingscote B. F.Reclassification of North American leptospiral isolates belonging to serogroups Mini and Sejroe by restriction endonuclease anlaysis.Am. J. Vet. Res.4719866166
    575.
    Thiermann A. B., Handsaker A. L., Moseley S. L., and Kingscote B.New method for classification of leptospiral isolates belonging to serogroup Pomona by restriction endonuclease analysis: serovar kennewicki.J. Clin. Microbiol.211985585587
    576.
    Thompson J. C. and Manktelow B. W.Pathogenesis and red blood cell destruction in haemoglobinaemic leptospirosis.J. Comp. Pathol.961986529540
    577.
    Tjalma R. A. and Galton M. M.Human leptospirosis in Iowa.Am. J. Trop. Med. Hyg.141965387396
    578.
    Tong M. J., Rosenberg E. B., Votteri B. A., and Tsai C.-C.Immunological response in leptospirosis. Report of three cases.Am. J. Trop. Med. Hyg.201971625630
    579.
    Torten M.LeptospirosisCRC handbook series in zoonoses, section A: bacterial, rickettsial and mycotic diseasesStoenner H. E., Torten M., and Kaplan W.I1979363420CRC PressBoca Raton, Fla
    580.
    Torten M., Shenberg E., and van der Hoeden J.The use of immunofluorescence in the diagnosis of human leptospirosis by a genus-specific antigen.J. Infect. Dis.1161966537543
    581.
    Trevejo R. T., Rigau-Perez J. G., Ashford D. A., McClure E. M., Jarquin-Gonzalez C., Amador J. J., de los Reyes J. O., Gonzalez A., Zaki S. R., Shieh W. J., McLean R. G., Nasci R. S., Weyant R. S., Bolin C. A., Bragg S. L., Perkins B. A., and Spiegel R. A.Epidemic leptospirosis associated with pulmonary hemorrhage—Nicaragua, 1995.J. Infect. Dis.178199814571463
    582.
    Tripathy D. N., Hanson L. E., and Jones F. C.Growth of Hebdomadis group of leptospires in solid medium.Am. J. Vet. Res.41198011531154
    583.
    Trueba G. A., Bolin C. A., and Zuerner R. L.Characterization of the periplasmic flagellum proteins of Leptospira interrogans.J. Bacteriol.174199247614768
    584.
    Trueba G. A., Bolin C. A., and Zuerner R. L.Cloning of the pfaP gene of Leptospira borgpetersenii.Gene1601995133134
    585.
    Turner L. H.Leptospirosis I.Trans. R. Soc. Trop. Med. Hyg.611967842855
    586.
    Turner L. H.Leptospirosis II. Serology.Trans. R. Soc. Trop. Med. Hyg.621968880889
    586a.
    Turner, L. H. 1969. Leptospirosis.i:231–235.
    587.
    Turner L. H.Leptospirosis III. Maintenance, isolation and demonstration of leptospires.Trans. R. Soc. Trop. Med. Hyg.641970623646
    588.
    Uhlenhuth P. and Fromme W.Experimentelle Untersuchungen über die sogenannte Weilsche Krankheit (ansteckende Gelbsucht).Med. Klin.44191512021203
    589.
    Uip D. E., Amato Neto V., and Duarte M. S.Diagnóstico precoce da leptospirose por demonstração de antı́genos através de exame imuno-histoquı́mino em músculo da panturrilha.Rev. Inst. Med. Trop. Sao Paulo341992375381
    590.
    Vanasco N. B., Sequeira G., Fontana M. L. D., Fusco S., Sequeira M. D., and Enria D.Descripción de un brote de leptospirosis en la ciudad de Santa Fe, Argentina, marzo–abril de 1998.Rev. Panam. Salud Publica720003540
    591.
    van Crevel R., Speelman P., Gravekamp C., and Terpstra W. J.Leptospirosis in travelers.Clin. Infect. Dis.191994132134
    592.
    van der Lelie J., van der Plas-Van Dalen C. M., and von dem Borne A. E.Platelet autoantibodies in septicaemia.Br. J. Haematol.581984755760
    593.
    Van Eys G. J. J. M., Gerritsen M. J., Korver H., Schoone G. J., Kroon C. C. M., and Terpstra W. J.Characterization of serovars of the genus Leptospira by DNA hybridization with hardjobovis and icterohaemorrhagiae recombinant probes with special attention to serogroup Sejroe.J. Clin. Microbiol.29199110421048
    594.
    Van Eys G. J. J. M., Gravekamp C., Gerritsen M. J., Quint W., Cornelissen M. T. E., ter Schegget J., and Terpstra W. J.Detection of leptospires in urine by the polymerase chain reaction.J. Clin. Microbiol.27198922582262
    595.
    Van Eys G. J. J. M., Zaal J., Schoone G. J., and Terpstra W. J.DNA hybridization with hardjobovis-specific recombinant probes as a method for type discrimination of Leptospira interrogans serovar hardjo.J. Gen. Microbiol.1341988567574
    596.
    van Thiel P. H.The leptospiroses.1948University of LeidenLeiden, The Netherlands
    597.
    Varfolomeeva A. A.Epidemiology and aetiology of an outbreak of leptospirosis.J. Microbiol. Epidemiol. Immunobiol.2819573843
    598.
    Vaughan C., Cronin C. C., Walsh E. K., and Whelton M.The Jarisch-Herxheimer reaction in leptospirosis.Postgrad. Med. J.701994118121
    599.
    Veloso I., Lopes M., Salas C., and Moreira E.A comparison of three DNA extractive procedures with Leptospira for polymerase chain reaction analysis.Mem. Inst. Oswaldo Cruz952000339343
    600.
    Vilaichone R. K., Mahachai V., and Wilde H.Acute acalculous cholecystitis in leptospirosis.J. Clin. Gastroenterol.291999280283
    601.
    Vinetz J. M., Glass G. E., Flexner C. E., Mueller P., and Kaslow D. C.Sporadic urban leptospirosis.Ann. Intern. Med.1251996794798
    602.
    Vinh T., Adler B., and Faine S.Glycolipoprotein cytotoxin from Leptospira interrogans serovar copenhageni.J. Gen. Microbiol.1321986111123
    603.
    Vinh T., Adler B., and Faine S.Ultrastructure and chemical composition of lipopolysaccharide extracted from Leptospira interrogans serovar copenhageni.J. Gen. Microbiol.1321986103109
    604.
    Vinh T., Adler B., and Faine S.The role of macrophages in the protection of mice against leptospirosis: in vitro and in vivo studies.Pathology141982463468
    605.
    Vinh T., Faine S., Handley C. J., and Adler B.Immunochemical studies of opsonic epitopes of the lipopolysaccharide of Leptospira interrogans serovar hardjo.FEMS Immunol. Med. Microbiol.8199499108
    606.
    Wagenaar J., Zuerner R. L., Alt D., and Bolin C. A.Comparison of polymerase chain reaction assays with bacteriologic culture, immunofluorescence, and nucleic acid hybridization for detection of Leptospira borgpetersenii serovar hardjo in urine of cattle.Am. J. Vet. Res.61200031620
    607.
    Wagenaar J. A., Segers R. P., and Van der Zeijst B. A.Rapid and specific detection of pathogenic Leptospira species by amplification of ribosomal sequences.Mol. Biotechnol.21994114
    608.
    Waitkins S.Maintenance of LeptospiraMaintenance of microorganisms.Kirsop B. E. and Snell J. J. S.19845762Academic PressLondon, U.K
    609.
    Waitkins S. A.Leptospirosis as an occupational disease.Br. J. Ind. Med.431986721725
    610.
    Waitkins S. A.An update on leptospirosis.Commun. Dis. Rep.44198434
    611.
    Waitkins S. A. and Buchan J.Leptospirosis in British cavers in Malaysia—the Sarawak experience.Isr. J. Vet. Med.431987346
    612.
    Waitkins S. A. and Hookey J.The detection of leptospires by a chemiluminescent immunoassay.J. Med. Microbiol.211986353356
    613.
    Wang B., Sullivan J., Sullivan G. W., and Mandell G. L.Interaction of leptospires with human polymorphonuclear neutrophils.Infect. Immun.441984459464
    614.
    Wang C., Ch'i C., and Lu F.Studies on anicteric leptospirosis. III. Roentgenologic observations of pulmonary changes.Chin. Med. J.841965298306
    615.
    Wang C., John L., Chang T., Cheng W., Luo M., and Hung A.Studies on anicteric leptospirosis. I. Clinical manifestations and antibiotic therapy.Chin. Med. J.841965283291
    616.
    Wanyangu S. W., Palmer M. F., Zochowski W. J., and Waitkins S. A.Comparison of the DIFCO and Patoc 1 slide antigens in the screening of leptospirosis.Comp. Immunol. Microbiol. Infect. Dis.101987155161
    617.
    Watt G., Alquiza L. M., Padre L. P., Tuazon M. L., and Laughlin L. W.The rapid diagnosis of leptospirosis: a prospective comparison of the dot enzyme-linked immunosorbent assay and the genus-specific microscopic agglutination test at different stages of illness.J. Infect. Dis.1571988840842
    618.
    Watt G., Padre L. P., Tuazon M., and Caluaquib C.Skeletal and cardiac muscle involvement in severe, late leptospirosis.J. Infect. Dis.1621990266269
    619.
    Watt G., Padre L. P., Tuazon M. L., Calubaquib C., Santiago E., Ranoa C. P., and Laughlin L. W.Placebo-controlled trial of intravenous penicillin for severe and late leptospirosis.Lanceti1988433435
    620.
    Watt G. and Warrell D. A.Leptospirosis and the Jarisch-Herxheimer reaction.Clin. Infect. Dis.20199514371438
    621.
    Weber A., Weber G., and Krauss H.Evaluation of the slide agglutination test for detection of leptospiral antibodies in serum samples of slaughter pigs.Zentbl. Bakteriol.2571984498500
    622.
    Weekers L. and Firket J.Les manifestations oculaires de la spirochétose ictéro-hémorragique.Arch. Ophthalmol.351916647665
    623.
    Weekes C. C., Everard C. O. R., and Levett P. N.Seroepidemiology of canine leptospirosis on the island of Barbados.Vet. Microbiol.511997215222
    624.
    Weil A.Ueber eine eigentümliche, mit Milztumor, Icterus und Nephritis einhergehende akute Infektionskrankheit.Dtsche. Arch. Klin. Med.391886209232
    625.
    Welsh J. and McClelland M.Fingerprinting genomes using PCR with arbitrary primers.Nucleic Acids Res.18199072137218
    625a.
    Weyant R. S., Bragg S. L., and Kaufman A. F.Leptospira and LeptonemaManual of clinical microbiology7th ed.Murray P. R., Baron E. J., Pfaller M. A., Tenover F. C., and Yolken R. H.1999739745ASM PressWashington, D.C.
    626.
    White F. H., Sulzer K. R., and Engel R. W.Isolations of Leptospira interrogans serovars hardjo, balcanica, and pomona from cattle at slaughter.Am. J. Vet. Res.43198211721173
    627.
    Wilkins E., Cope A., and Waitkins S.Rapids, rafts, and rats.Lancetii1988283284
    628.
    Williams H. R., Murphy W. J., McCroan J. E., Starr L. E., and Ward M. K.An epidemic of Canicola fever in man with the demonstration of Leptospira canicola infection in dogs, swine and cattle: clinical and epidemiological studies.Am. J. Hyg.6419564658
    629.
    Williams J. G. K., Kubelik A. R., Livak K. J., Rafalski J. A., and Tingey S. V.DNA polymorphisms amplified by arbitrary primers are useful as genetic markers.Nucleic Acids Res.18199065316535
    630.
    Wilmaers L. and Renaux E.Quarante-sept cas de spirochétose ictéro-hémorragique.Arch. Med. Belg.701917115207
    631.
    Winearls C. G., Chan L., Coghlan J. D., Ledingham J. G. G., and Oliver D. O.Acute renal failure due to leptospirosis: clinical features and outcome in six cases.Q. J. Med.531984487495
    632.
    Winslow W. E., Merry D. J., Pirc M. L., and Devine P. L.Evaluation of a commercial enzyme-linked immunosorbent assay for detection of immunoglobulin M antibody in diagnosis of human leptospiral infection.J. Clin. Microbiol.35199719381942
    633.
    Winter R. J. D., Richardson A., Lehner M. J., and Hoffbrand B. I.Lung abscess and reactive arthritis: rare complications of leptospirosis.BMJ2881984448449
    634.
    Wolff J. W.The laboratory diagnosis of leptospirosis. C. C.1954ThomasSpringfield, Ill
    635.
    Wolff J. W. and Bohlander H. J.Evaluation of Galton's macroscopic slide test for the serodiagnosis of leptospirosis in human serum samples.Ann. Soc. Belg. Med. Trop.461966123132
    636.
    Wong M. L., Kaplan S., Dunkle L. M., Stechenberg B. W., and Feigin R. D.Leptospirosis: a childhood disease.J. Pediatr.901977532537
    637.
    Woo T. H. S., Patel B. K. C., Smythe L. D., Norris M. A., Symonds M. L., and Dohnt M. F.Identification of pathogenic Leptospira by TaqMan probe in a lightcycler.Anal. Biochem.2561998132134
    638.
    Woo T. H. S., Patel B. K. C., Smythe L. D., Symonds M. L., Norris M. A., and Dohnt M. F.Comparison of two PCR methods for rapid identification of Leptospira genospecies interrogans.FEMS Microbiol. Lett.1551997169177
    639.
    Woo T. H. S., Smythe L. D., Symonds M. L., Norris M. A., Dohnt M. F., and Patel B. K. C.Rapid distinction between Leptospira interrogans and Leptospira biflexa by PCR amplification of 23S ribosomal DNA.FEMS Microbiol. Lett.1501997918
    640.
    Woodward M. J. and Redstone J. S.Deoxynucleotide sequence conservation of the endoflagellin subunit protein gene, flaB, within the genus Leptospira.Vet. Microbiol.401994239251
    641.
    Woodward M. J. and Sullivan G. J.Nucleotide sequence of a repetitive element isolated from Leptospira interrogans serovar hardjo type hardjo-bovis.J. Gen. Microbiol.137199111011109
    642.
    Woodward M. J., Swallow C., Kitching A., Dalley C., and Sayers A. R.Leptospira hardjo serodiagnosis: a comparison of MAT, ELISA and immunocomb.Vet. Rec.1411997603604
    643.
    Woodward M. J., Sullivan G. J., Palmer N. M. A., Woolley J. C., and Redstone J. S.Development of a PCR test specific for Leptospira hardjo genotype bovis.Vet. Rec.1281991282283
    644.
    Woodward T.The protean mainfestations of leptospirosisSymposium on the leptospiroses. U.S.19535768Government Printing OfficeWashington, D.C.
    645.
    World Health OrganizationLeptospirosis, India: report of the investigation of a post-cyclone outbreak in Orissa, November 1999.Wkly. Epidemiol. Rec. WHO752000217223
    646.
    World Health OrganizationLeptospirosis worldwide, 1999.Wkly. Epidemiol. Rec.741999237242
    647.
    Wu W., Bao L., Wu Q., Li S., Huang W., Wan B., Zhang M., Xiong Q., and Fang Z.16S rRNA gene PCR-SSCP analysis of the reference strains from 15 serovars (14 serogroups) of pathogenic leptospires in China.Hua Hsi I Ko Ta Hsueh Hsueh Pao2719961720
    648.
    Wylie J. A. H. and Vincent E.The sensitivity of organisms of the genus Leptospira to penicillin and streptomycin.J. Pathol. Bacteriol.591947247254
    649.
    Xiao J., Dai B., Chai J., and Yu L.The study on genome size of leptospires.Hua Hsi I Ko Ta Hsueh Pao211990362365
    650.
    Ximin L., Xuzhong R., Zhuan C., Burun Y., Shangpu H., and Yunhe G.Moyamoya disease caused by leptospiral cerebral arteritis.Chin. Med. J.931980599604
    651.
    Yam P. A., Miller N. G., and White R. J.A leptospiral factor producing a cytopathic effect on L cells.J. Infect. Dis.1221970310317
    652.
    Yamashiro-Kanashiro E. H., Benard G., Sato M. N., Seguro A. C., and Duarte A. J. S.Cellular immune response analysis of patients with leptospirosis.Am. J. Trop. Med. Hyg.451991138145
    653.
    Yan K. T., Ellis W. A., Mackie D. P., Taylor M. J., McDowell S. W., and Montgomery J. M.Development of an ELISA to detect antibodies to a protective lipopolysaccharide fraction of Leptospira borgpetersenii serovar hardjo in cattle.Vet. Microbiol.691999173187
    654.
    Yan K. T., Ellis W. A., Montgomery J. M., Taylor M. J., Mackie D. P., and McDowell S. W.Development of an immunomagnetic antigen capture system for detecting leptospires in bovine urine.Res. Vet. Sci.641998119124
    655.
    Yanagihara Y., Kojima T., and Mifuchi I.Hemolytic activity of Leptospira interrogans serovar canicola cultured in protein-free medium.Microbiol. Immunol.261982547556
    656.
    Yasuda P. H., Hoshino-Shimizu S., Yamashiro E. H., and de Brito T.Experimental leptospirosis (L. interrogans serovar icterohaemorrhagiae) of the guinea pig: leptospiral antigen, gamma globulin and complement C3 detection in the kidney.Exp. Pathol.2919863543
    657.
    Yasuda P. H., Sakata E. E., Shikanai-Yasuda M. A., Vasconcelos S. d. A., Romero E. C., da Silva M. V., and Carrasco S.Evaluation of counterimmunoelectrophoresis with antigens of icterohaemorrhagiae and patoc serovars in the serodiagnosis of human leptospirosis.Rev. Inst. Med. Trop. Sao Paulo331991497502
    658.
    Yasuda P. H., Steigerwalt A. G., Sulzer K. R., Kaufmann A. F., Rogers F., and Brenner D. J.Deoxyribonucleic acid relatedness between serogroups and serovars in the family Leptospiraceae with proposals for seven new Leptospira species.Int. J. Syst. Bacteriol.371987407415
    659.
    Yersin C., Bovet P., Mérien F., Clément J., Laille M., Van Ranst M., and Perolat P.Pulmonary haemorrhage as a predominant cause of death in leptospirosis in Seychelles.Trans. R. Soc. Trop. Med. Hyg.9420007176
    660.
    Yersin C., Bovet P., Mérien F., Wong T., Panowsky J., and Perolat P.Human leptospirosis in the Seychelles (Indian Ocean): a population-based study.Am. J. Trop. Med. Hyg.591998933940
    661.
    Yersin C., Bovet P., Smits H. L., and Perolat P.Field evaluation of a one-step dipstick assay for the diagnosis of human leptospirosis in the Seychelles.Trop. Med. Int. Health419993845
    662.
    Younes-Ibrahim M., Burth P., Faria M. V., Buffin-Meyer B., Marsy S., Barlet-Bas C., Cheval L., and Doucet A.Inhibition of Na,K-ATPase by an endotoxin extracted from Leptospira interrogans: a possible mechanism for the physiopathology of leptospirosis.C. R. Acad. Sci. III3181995619625
    663.
    Yuri K., Takamoto Y., Okada M., Hiramune T., Kikuchi N., and Yanagawa R.Chemotaxis of leptospires to hemoglobin in relation to virulence.Infect. Immun.61199322702272
    664.
    Zaki S. R., Shieh W.-J., and the Epidemic Working GroupLeptospirosis associated with outbreak of acute febrile illness and pulmonary haemorrhage, Nicaragua, 1995.Lancet3471996535
    665.
    Zaki S. R. and Spiegel R. A.LeptospirosisPathology of emerging infections 2.Nelson A. M. and Horsburgh C. R.19987392American Society for MicrobiologyWashington, D.C.
    666.
    Zaltzman M., Kallenbach J. M., Goss G. D., Lewis M., Zwi S., and Gear J. H. S.Adult respiratory distress syndrome in Leptospira canicola infection.BMJ2831981519520
    667.
    Zhang Y., Li S., and Dai B.Amplified 23S rRNA gene of 52 strains of Leptospira and detection of leptospiral DNA in 55 patients by PCR.Hua Hsi I Ko Ta Hsueh Hsueh Pao241993262267
    668.
    Zuerner R. L.Nucleotide sequence analysis of IS1533 from Leptospira borgpetersenii: identification and expression of two IS-encoded proteins.Plasmid311994111
    669.
    Zuerner R. L.Physical map of the chromosomal and plasmid DNA comprising the genome of Leptospira interrogans.Nucleic Acids Res.19199148574860
    670.
    Zuerner R. L., Alt D., and Bolin C. A.IS1533-based PCR assay for identification of Leptospira interrogans sensu lato.J. Clin. Microbiol.33199532843289
    671.
    Zuerner R. L. and Bolin C. A.Differentiation of Leptospira interrogans isolates by IS1500 hybridization and PCR assays.J. Clin. Microbiol.35199726122617
    672.
    Zuerner R. L. and Bolin C. A.Nucleic acid probe characterizes Leptospira interrogans serovars by restriction fragment length polymorphisms.Vet. Microbiol.241990355366
    673.
    Zuerner R. L. and Bolin C. A.Repetitive sequence element cloned from Leptospira interrogans serovar hardjo type hardjo-bovis provides a sensitive diagnostic probe for bovine leptospirosis.J. Clin. Microbiol.26198824952500
    674.
    Zuerner R. L. and Charon N. W.Nucleotide sequence analysis of a gene cloned from Leptopsira biflexa serovar patoc which complements an argE defect in Escherichia coli.J. Bacteriol.170198845484554
    675.
    Zuerner R. L., Ellis W. A., Bolin C. A., and Montgomery J. M.Restriction fragment length polymorphisms distinguish Leptospira borgpetersenii serovar hardjo type hardjo-bovis isolates from different geographical locations.J. Clin. Microbiol.311993578583
    676.
    Zuerner R. L., Hartskeerl R. A., van de Kemp H., and Bal A. E.Characterization of the Leptospira interrogans S10-spc-α operon.FEMS Microbiol. Lett.1822000303308
    677.
    Zuerner R. L., Herrmann J. L., and Saint Girons I.Comparison of genetic maps for two Leptospira interrogans serovars provides evidence for two chromosomes and intraspecies heterogeneity.J. Bacteriol.175199354455451

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    Volume 14Number 21 April 2001
    Pages: 296 - 326

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    Paul N. Levett
    University of the West Indies, School of Clinical Medicine & Research, and Leptospira Laboratory, Ministry of Health, Barbados

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  • Clinical Microbiology ReviewsArticle
    Coagulase-Negative Staphylococci

    SUMMARY

    The definition of the heterogeneous group of coagulase-negative staphylococci (CoNS) is still based on diagnostic procedures that fulfill the clinical need to differentiate between Staphylococcus aureus and those staphylococci classified historically as being less or nonpathogenic. Due to patient- and procedure-related changes, CoNS now represent one of the major nosocomial pathogens, with S. epidermidis and S. haemolyticus being the most significant species. They account substantially for foreign body-related infections and infections in preterm newborns. While S. saprophyticus has been associated with acute urethritis, S. lugdunensis has a unique status, in some aspects resembling S. aureus in causing infectious endocarditis. In addition to CoNS found as food-associated saprophytes, many other CoNS species colonize the skin and mucous membranes of humans and animals and are less frequently involved in clinically manifested infections. This blurred gradation in terms of pathogenicity is reflected by species- and strain-specific virulence factors and the development of different host-defending strategies. Clearly, CoNS possess fewer virulence properties than S. aureus, with a respectively different disease spectrum. In this regard, host susceptibility is much more important. Therapeutically, CoNS are challenging due to the large proportion of methicillin-resistant strains and increasing numbers of isolates with less susceptibility to glycopeptides.

    REFERENCES

    1.
    Kloos WE and Bannerman TL. 1994. Update on clinical significance of coagulase-negative staphylococci. Clin. Microbiol. Rev. 7:117–140.
    2.
    Pfaller MA and Herwaldt LA. 1988. Laboratory, clinical, and epidemiological aspects of coagulase-negative staphylococci. Clin. Microbiol. Rev. 1:281–299.
    3.
    Taponen S and Pyörälä S. 2009. Coagulase-negative staphylococci as cause of bovine mastitis—not so different from Staphylococcus aureus? Vet. Microbiol. 134:29–36.
    4.
    Irlinger F. 2008. Safety assessment of dairy microorganisms: coagulase-negative staphylococci. Int. J. Food Microbiol. 126:302–310.
    5.
    Billroth T. 1874. Untersuchungen über die Vegetationsformen von Coccobacteria septica und den Antheil, welchen sie an der Entstehung und Verbreitung der accidentellen Wundkrankheiten haben: Versuch einer wissenschaftlichen Kritik der verschiedenen Methoden antiseptischer Wundbehandlung. G Reimer, Berlin, Germany.
    6.
    Ogston A. 1882. Micrococcus poisoning. J. Anat. Physiol. 17:24–58.
    7.
    Ogston A. 1880. Ueber Abscesse. Arch. Klin. Chir. 25:588.
    8.
    Rosenbach FJ. 1884. Micro-Organismen bei den Wund-Infections-Krankheiten des Menschen. J F Bergmann, Wiesbaden, Germany.
    9.
    Nocht E, Metschnikoff E, Schwarz O, Weichselbaum A, and Weyl T. 1900. Handbuch der Hygiene. Neunter Band. Aetiologie und Prophylaxe der Infektionskrankheiten. G Fischer, Jena, Germany.
    10.
    Welch WH. 1891. Conditions underlying the infection of wounds. Am. J. Med. Sci. 102:439–465.
    11.
    Winslow CEA and Winslow AR. 1908. The systematic relationships of the Coccaceae. John Wiley and Sons, New York, NY.
    12.
    Fairbrother RW. 1940. Coagulase production as a criterion for the classification of the staphylococci. J. Pathol. Bacteriol. 50:83–88.
    13.
    Shaw C, Stitt JM, and Cowan ST. 1951. Staphylococci and their classification. J. Gen. Microbiol. 5:1010–1023.
    14.
    Maskell R. 1974. Importance of coagulase-negative staphylococci as pathogens in the urinary tract. Lancet 303:1155–1158.
    15.
    Buchanan RE and Gibbons NE. 1974. Bergey's manual of determinative bacteriology, 8th ed. Williams & Wilkins, Baltimore, MD.
    16.
    Euzéby JP. 1997. List of bacterial names with standing in nomenclature: a folder available on the internet. Int. J. Syst. Bacteriol. 47:590–592.
    17.
    De Bel A, Van Hoorde K, Wybo I, Vandoorslaer K, Echahidi F, De Brandt E, Schumann P, Ieven M, Soetens O, Piérard D, and Vandamme P. 2013. Staphylococcus jettensis sp. nov., a coagulase-negative staphylococcal species isolated from human clinical specimens. Int. J. Syst. Evol. Microbiol. 63:3250–3256.
    18.
    Trülzsch K, Grabein B, Schumann P, Mellmann A, Antonenka U, Heesemann J, and Becker K. 2007. Staphylococcus pettenkoferi sp. nov., a novel coagulase-negative staphylococcal species isolated from human clinical specimens. Int. J. Syst. Evol. Microbiol. 57:1543–1548.
    19.
    Al Masalma M, Raoult D, and Roux V. 2010. Staphylococcus massiliensis sp. nov., isolated from a human brain abscess. Int. J. Syst. Evol. Microbiol. 60:1066–1072.
    20.
    Pantucek R, Svec P, Dajcs JJ, Machová I, Cernohlavkova J, Sedo O, Gelbicova T, Maslanova I, Doskar J, Zdrahal Z, Ruzickova V, and Sedlacek I. 2013. Staphylococcus petrasii sp. nov. including S. petrasii subsp. petrasii subsp. nov. and S. petrasii subsp. croceilyticus subsp. nov., isolated from human clinical specimens and human ear infections. Syst. Appl. Microbiol. 36:90–95.
    21.
    Tang YW, Han J, McCormac MA, Li H, and Stratton CW. 2008. Staphylococcus pseudolugdunensis sp. nov., a pyrrolidonyl arylamidase/ornithine decarboxylase-positive bacterium isolated from blood cultures. Diagn. Microbiol. Infect. Dis. 60:351–359.
    22.
    Svec P, Vancanneyt M, Sedlácek I, Engelbeen K, Stetina V, Swings J, and Petrás P. 2004. Reclassification of Staphylococcus pulvereri Zakrzewska-Czerwinska et al. 1995 as a later synonym of Staphylococcus vitulinus Webster et al. 1994. Int. J. Syst. Evol. Microbiol. 54:2213–2215.
    23.
    Kloos WE, Ballard DN, George CG, Webster JA, Hubner RJ, Ludwig W, Schleifer KH, Fiedler F, and Schubert K. 1998. Delimiting the genus Staphylococcus through description of Macrococcus caseolyticus gen. nov., comb. nov. and Macrococcus equipercicus sp. nov., and Macrococcus bovicus sp. nov. and Macrococcus carouselicus sp. nov. Int. J. Syst. Bacteriol. 48:859–877.
    24.
    de la Fuente R, Suarez G, Ruiz Santa Quiteria JA, Meugnier H, Bes M, Freney J, and Fleurette J. 1992. Identification of coagulase negative staphylococci isolated from lambs as Staphylococcus caseolyticus. Comp. Immunol. Microbiol. Infect. Dis. 15:47–52.
    25.
    Ludwig W, Schleifer KH, and Whitman WB. 2009. Revised road map to the phylum Firmicutes. In De Vos P, Garrity G, Jones D, Krieg NR, Ludwig W, Rainey FA, Schleifer KH, and Whitman WB (ed), Bergey's manual of systematic bacteriology, 2nd ed, vol 3. The Firmicutes. Springer, New York, NY.
    26.
    Garrity GM, Winters M, and Searles DB. 2001. Taxonomic outline of the procaryotes, p 1–318. In Boone DR, Castenholz RW, and Garrity GM (ed), Bergey's manual of systematic bacteriology, 2nd ed, release 1.0. Springer-Verlag, New York, NY.
    27.
    Alves M, Nogueira C, de Magalhães-Sant'Ana A, Chung AP, Morais PV, and da Costa MS. 2008. Nosocomiicoccus ampullae gen. nov., sp. nov., isolated from the surface of bottles of saline solution used in wound cleansing. Int. J. Syst. Evol. Microbiol. 58:2939–2944.
    28.
    Stackebrandt E, Rainey FA, and Ward-Rainey NL. 1997. Proposal for a new hierarchic classification system, Actinobacteria classis nov. Int. J. Syst. Bacteriol. 47:479–491.
    29.
    Euzeby J. 2010. Validation list no. 132. List of new names and new combinations previously effectively, but not validly, published. Int. J. Syst. Evol. Microbiol. 60:469–472.
    30.
    Stackebrandt E, Koch C, Gvozdiak O, and Schumann P. 1995. Taxonomic dissection of the genus Micrococcus: Kocuria gen. nov., Nesterenkonia gen. nov., Kytococcus gen. nov., Dermacoccus gen. nov., and Micrococcus Cohn 1872 gen. emend. Int. J. Syst. Bacteriol. 45:682–692.
    31.
    Stackebrandt E and Schumann P. 2000. Description of Bogoriellaceae fam. nov., Dermacoccaceae fam. nov., Rarobacteraceae fam. nov. and Sanguibacteraceae fam. nov. and emendation of some families of the suborder Micrococcineae. Int. J. Syst. Evol. Microbiol. 50:1279–1285.
    32.
    Lamers RP, Muthukrishnan G, Castoe TA, Tafur S, Cole AM, and Parkinson CL. 2012. Phylogenetic relationships among Staphylococcus species and refinement of cluster groups based on multilocus data. BMC Evol. Biol. 12:171.
    33.
    Grice EA and Segre JA. 2011. The skin microbiome. Nat. Rev. Microbiol. 9:244–253.
    34.
    Marples MJ. 1974. The normal microbial flora of the skin. Soc. Appl. Bacteriol. Symp. Ser. 3:7–12.
    35.
    Evans CA, Smith WM, Johnston EA, and Giblett ER. 1950. Bacterial flora of the normal human skin. J. Invest. Dermatol. 15:305–324.
    36.
    Grice EA, Kong HH, Conlan S, Deming CB, Davis J, Young AC, NISC Comparative Sequencing Program, Bouffard GG, Blakesley RW, Murray PR, Green ED, Turner ML, and Segre JA. 2009. Topographical and temporal diversity of the human skin microbiome. Science 324:1190–1192.
    37.
    Costello EK, Lauber CL, Hamady M, Fierer N, Gordon JI, and Knight R. 2009. Bacterial community variation in human body habitats across space and time. Science 326:1694–1697.
    38.
    Wos-Oxley ML, Plumeier I, von Eiff C, Taudien S, Platzer M, Vilchez-Vargas R, Becker K, and Pieper DH. 2010. A poke into the diversity and associations within human anterior nare microbial communities. ISME J. 4:839–851.
    39.
    Graham JE, Moore JE, Jiru X, Moore JE, Goodall EA, Dooley JS, Hayes VE, Dartt DA, Downes CS, and Moore TC. 2007. Ocular pathogen or commensal: a PCR-based study of surface bacterial flora in normal and dry eyes. Invest. Ophthalmol. Vis. Sci. 48:5616–5623.
    40.
    Willcox MD. 2013. Characterization of the normal microbiota of the ocular surface. Exp. Eye Res. 117:99–105.
    41.
    Kong HH and Segre JA. 2012. Skin microbiome: looking back to move forward. J. Invest. Dermatol. 132:933–939.
    42.
    Iwase T, Uehara Y, Shinji H, Tajima A, Seo H, Takada K, Agata T, and Mizunoe Y. 2010. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 465:346–349.
    43.
    Schleifer KH and Kloos WE. 1975. Isolation and characterization of staphylococci from human skin. I. Amended descriptions of Staphylococcus epidermidis and Staphylococcus saprophyticus and descriptions of three new species: Staphylococcus cohnii, Staphylococcus haemolyticus, and Staphylococcus xylosus. Int. J. Syst. Bacteriol. 25:50–61.
    44.
    Kloos WE and Musselwhite MS. 1975. Distribution and persistence of Staphylococcus and Micrococcus species and other aerobic bacteria on human skin. Appl. Microbiol. 30:381–385.
    45.
    Kloos WE and Schleifer KH. 1975. Isolation and characterization of staphylococci from human skin. II. Description of four new species: Staphylococcus warneri, Staphylococcus capitis, Staphylococcus hominis, and Staphylococcus simulans. Int. J. Syst. Bacteriol. 25:62–79.
    46.
    Kloos WE and Schleifer KH. 1983. Staphylococcus auricularis sp. nov.: an inhabitant of the human external ear. Int. J. Syst. Bacteriol. 33:9–14.
    47.
    Bieber L and Kahlmeter G. 2010. Staphylococcus lugdunensis in several niches of the normal skin flora. Clin. Microbiol. Infect. 16:385–388.
    48.
    van der Mee-Marquet N, Achard A, Mereghetti L, Danton A, Minier M, and Quentin R. 2003. Staphylococcus lugdunensis infections: high frequency of inguinal area carriage. J. Clin. Microbiol. 41:1404–1409.
    49.
    Bieber L and Kahlmeter G. 2010. Staphylococcus lugdunensis in several niches of the normal skin flora. Clin. Microbiol. Infect. 16:385–388.
    50.
    Rupp ME, Soper DE, and Archer GL. 1992. Colonization of the female genital tract with Staphylococcus saprophyticus. J. Clin. Microbiol. 30:2975–2979.
    51.
    Schneider PF and Riley TV. 1996. Staphylococcus saprophyticus urinary tract infections: epidemiological data from Western Australia. Eur. J. Epidemiol. 12:51–54.
    52.
    Nys S, van Merode T, Bartelds AI, and Stobberingh EE. 2006. Urinary tract infections in general practice patients: diagnostic tests versus bacteriological culture. J. Antimicrob. Chemother. 57:955–958.
    53.
    Hedman P, Ringertz O, Lindstrom M, and Olsson K. 1993. The origin of Staphylococcus saprophyticus from cattle and pigs. Scand. J. Infect. Dis. 25:57–60.
    54.
    Hedman P, Ringertz O, Eriksson B, Kvarnfors P, Andersson M, Bengtsson L, and Olsson K. 1990. Staphylococcus saprophyticus found to be a common contaminant of food. J. Infect. 21:11–19.
    55.
    Faria C, Vaz-Moreira I, Serapicos E, Nunes OC, and Manaia CM. 2009. Antibiotic resistance in coagulase negative staphylococci isolated from wastewater and drinking water. Sci. Total Environ. 407:3876–3882.
    56.
    Lina B, Vandenesch F, Etienne J, Kreiswirth B, and Fleurette J. 1992. Comparison of coagulase-negative staphylococci by pulsed-field electrophoresis. FEMS Microbiol. Lett. 71:133–138.
    57.
    Lang S, Livesley MA, Lambert PA, Elliott J, and Elliott TS. 1999. The genomic diversity of coagulase-negative staphylococci associated with nosocomial infections. J. Hosp. Infect. 43:187–193.
    58.
    Wisplinghoff H, Rosato AE, Enright MC, Noto M, Craig W, and Archer GL. 2003. Related clones containing SCCmec type IV predominate among clinically significant Staphylococcus epidermidis isolates. Antimicrob. Agents Chemother. 47:3574–3579.
    59.
    Schoenfelder SM, Lange C, Eckart M, Hennig S, Kozytska S, and Ziebuhr W. 2010. Success through diversity—how Staphylococcus epidermidis establishes as a nosocomial pathogen. Int. J. Med. Microbiol. 300:380–386.
    60.
    Thomas JC, Vargas MR, Miragaia M, Peacock SJ, Archer GL, and Enright MC. 2007. Improved multilocus sequence typing scheme for Staphylococcus epidermidis. J. Clin. Microbiol. 45:616–619.
    61.
    Kozitskaya S, Olson ME, Fey PD, Witte W, Ohlsen K, and Ziebuhr W. 2005. Clonal analysis of Staphylococcus epidermidis isolates carrying or lacking biofilm-mediating genes by multilocus sequence typing. J. Clin. Microbiol. 43:4751–4757.
    62.
    Miragaia M, Thomas JC, Couto I, Enright MC, and de Lencastre H. 2007. Inferring a population structure for Staphylococcus epidermidis from multilocus sequence typing data. J. Bacteriol. 189:2540–2552.
    63.
    Jamaluddin TZ, Kuwahara-Arai K, Hisata K, Terasawa M, Cui L, Baba T, Sotozono C, Kinoshita S, Ito T, and Hiramatsu K. 2008. Extreme genetic diversity of methicillin-resistant Staphylococcus epidermidis strains disseminated among healthy Japanese children. J. Clin. Microbiol. 46:3778–3783.
    64.
    Mendes RE, Deshpande LM, Costello AJ, and Farrell DJ. 2012. Molecular epidemiology of Staphylococcus epidermidis clinical isolates from U.S. hospitals. Antimicrob. Agents Chemother. 56:4656–4661.
    65.
    Gordon RJ, Miragaia M, Weinberg AD, Lee CJ, Rolo J, Giacalone JC, Slaughter MS, Pappas P, Naka Y, Tector AJ, de Lencastre H, and Lowy FD. 2012. Staphylococcus epidermidis colonization is highly clonal across US cardiac centers. J. Infect. Dis. 205:1391–1398.
    66.
    Widerström M, Wiström J, Ek E, Edebro H, and Monsen T. 2011. Near absence of methicillin-resistance and pronounced genetic diversity among Staphylococcus epidermidis isolated from healthy persons in northern Sweden. APMIS 119:505–512.
    67.
    Francois P, Hochmann A, Huyghe A, Bonetti EJ, Renzi G, Harbarth S, Klingenberg C, Pittet D, and Schrenzel J. 2008. Rapid and high-throughput genotyping of Staphylococcus epidermidis isolates by automated multilocus variable-number of tandem repeats: a tool for real-time epidemiology. J. Microbiol. Methods 72:296–305.
    68.
    Petti CA, Simmon KE, Miro JM, Hoen B, Marco F, Chu VH, Athan E, Bukovski S, Bouza E, Bradley S, Fowler VG, Giannitsioti E, Gordon D, Reinbott P, Korman T, Lang S, Garcia-de la-Maria C, Raglio A, Morris AJ, Plesiat P, Ryan S, Doco-Lecompte T, Tripodi F, Utili R, Wray D, Federspiel JJ, Boisson K, Reller LB, Murdoch DR, and Woods CW. 2008. Genotypic diversity of coagulase-negative staphylococci causing endocarditis: a global perspective. J. Clin. Microbiol. 46:1780–1784.
    69.
    Miragaia M, Couto I, and de Lencastre H. 2005. Genetic diversity among methicillin-resistant Staphylococcus epidermidis (MRSE). Microb. Drug Resist. 11:83–93.
    70.
    Ruppé E, Barbier F, Mesli Y, Maiga A, Cojocaru R, Benkhalfat M, Benchouk S, Hassaine H, Maiga I, Diallo A, Koumaré AK, Ouattara K, Soumaré S, Dufourcq JB, Nareth C, Sarthou JL, Andremont A, and Ruimy R. 2009. Diversity of staphylococcal cassette chromosome mec structures in methicillin-resistant Staphylococcus epidermidis and Staphylococcus haemolyticus strains among outpatients from four countries. Antimicrob. Agents Chemother. 53:442–449.
    71.
    Zong Z, Peng C, and Lü X. 2011. Diversity of SCCmec elements in methicillin-resistant coagulase-negative staphylococci clinical isolates. PLoS One 6:e20191.
    72.
    Miragaia M, Carriço JA, Thomas JC, Couto I, Enright MC, and de Lencastre H. 2008. Comparison of molecular typing methods for characterization of Staphylococcus epidermidis: proposal for clone definition. J. Clin. Microbiol. 46:118–129.
    73.
    Köser CU, Holden MT, Ellington MJ, Cartwright EJ, Brown NM, Ogilvy-Stuart AL, Hsu LY, Chewapreecha C, Croucher NJ, Harris SR, Sanders M, Enright MC, Dougan G, Bentley SD, Parkhill J, Fraser LJ, Betley JR, Schulz-Trieglaff OB, Smith GP, and Peacock SJ. 2012. Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. N. Engl. J. Med. 366:2267–2275.
    74.
    Takeuchi F, Watanabe S, Baba T, Yuzawa H, Ito T, Morimoto Y, Kuroda M, Cui L, Takahashi M, Ankai A, Baba S, Fukui S, Lee JC, and Hiramatsu K. 2005. Whole-genome sequencing of Staphylococcus haemolyticus uncovers the extreme plasticity of its genome and the evolution of human-colonizing staphylococcal species. J. Bacteriol. 187:7292–7308.
    75.
    Kresken M, Becker K, Seifert H, Leitner E, Körber-Irrgang B, von Eiff C, and Löschmann PA. 2011. Resistance trends and in vitro activity of tigecycline and 17 other antimicrobial agents against Gram-positive and Gram-negative organisms, including multidrug-resistant pathogens, in Germany. Eur. J. Clin. Microbiol. Infect. Dis. 30:1095–1103.
    76.
    Ma XX, Wang EH, Liu Y, and Luo EJ. 2011. Antibiotic susceptibility of coagulase-negative staphylococci (CoNS): emergence of teicoplanin-non-susceptible CoNS strains with inducible resistance to vancomycin. J. Med. Microbiol. 60:1661–1668.
    77.
    Lepainteur M, Royer G, Bourrel AS, Romain O, Duport C, Doucet-Populaire F, and Decousser JW. 2013. Prevalence of resistance to antiseptics and mupirocin among invasive coagulase-negative staphylococci from very preterm neonates in NICU: the creeping threat? J. Hosp. Infect. 83:333–336.
    78.
    Dimitriou G, Fouzas S, Giormezis N, Giannakopoulos I, Tzifas S, Foka A, Anastassiou DE, Spiliopoulou I, and Mantagos S. 2011. Clinical and microbiological profile of persistent coagulase-negative staphylococcal bacteraemia in neonates. Clin. Microbiol. Infect. 17:1684–1690.
    79.
    de Silva GD, Kantzanou M, Justice A, Massey RC, Wilkinson AR, Day NP, and Peacock SJ. 2002. The ica operon and biofilm production in coagulase-negative staphylococci associated with carriage and disease in a neonatal intensive care unit. J. Clin. Microbiol. 40:382–388.
    80.
    Foka A, Chini V, Petinaki E, Kolonitsiou F, Anastassiou ED, Dimitracopoulos G, and Spiliopoulou I. 2006. Clonality of slime-producing methicillin-resistant coagulase-negative staphylococci disseminated in the neonatal intensive care unit of a university hospital. Clin. Microbiol. Infect. 12:1230–1233.
    81.
    Monsen T, Karlsson C, and Wiström J. 2005. Spread of clones of multidrug-resistant, coagulase-negative staphylococci within a university hospital. Infect. Control Hosp. Epidemiol. 26:76–80.
    82.
    Widerström M, Monsen T, Karlsson C, and Wiström J. 2006. Molecular epidemiology of meticillin-resistant coagulase-negative staphylococci in a Swedish county hospital: evidence of intra- and interhospital clonal spread. J. Hosp. Infect. 64:177–183.
    83.
    Liakopoulos V, Petinaki E, Efthimiadi G, Klapsa D, Giannopoulou M, Dovas S, Eleftheriadis T, Mertens PR, and Stefanidis I. 2008. Clonal relatedness of methicillin-resistant coagulase-negative staphylococci in the haemodialysis unit of a single university centre in Greece. Nephrol. Dial. Transplant. 23:2599–2603.
    84.
    Mazzariol A, Lo CG, Kocsis E, Maccacaro L, Fontana R, and Cornaglia G. 2012. Outbreak of linezolid-resistant Staphylococcus haemolyticus in an Italian intensive care unit. Eur. J. Clin. Microbiol. Infect. Dis. 31:523–527.
    85.
    Brito DV, von Dolinger EJ, Abdallah VO, Darini AL, and Gontijo Filho PP. 2009. Two outbreaks of mixed etiology associated with central venous catheters inserted by phlebotomy in critical neonates. Braz. J. Infect. Dis. 13:177–182.
    86.
    Wang SM, Liu CC, Tseng HW, Yang YJ, Lin CH, Huang AH, and Wu YH. 1999. Staphylococcus capitis bacteremia of very low birth weight premature infants at neonatal intensive care units: clinical significance and antimicrobial susceptibility. J. Microbiol. Immunol. Infect. 32:26–32.
    87.
    Krediet TG, Mascini EM, van Rooij E, Vlooswijk J, Paauw A, Gerards LJ, and Fleer A. 2004. Molecular epidemiology of coagulase-negative staphylococci causing sepsis in a neonatal intensive care unit over an 11-year period. J. Clin. Microbiol. 42:992–995.
    88.
    von Eiff C, Arciola CR, Montanaro L, Becker K, and Campoccia D. 2006. Emerging Staphylococcus species as new pathogens in implant infections. Int. J. Artif. Organs 29:360–367.
    89.
    Spanu T, Sanguinetti M, Ciccaglione D, D'Inzeo T, Romano L, Leone F, and Fadda G. 2003. Use of the VITEK 2 system for rapid identification of clinical isolates of staphylococci from bloodstream infections. J. Clin. Microbiol. 41:4259–4263.
    90.
    Huang CR, Lu CH, Wu JJ, Chang HW, Chien CC, Lei CB, and Chang WN. 2005. Coagulase-negative staphylococcal meningitis in adults: clinical characteristics and therapeutic outcomes. Infection 33:56–60.
    91.
    Shin JH, Kim SH, Jeong HS, Oh SH, Kim HR, Lee JN, Yoon YC, Kim YW, and Kim YH. 2011. Identification of coagulase-negative staphylococci isolated from continuous ambulatory peritoneal dialysis fluid using 16S ribosomal RNA, tuf, and sodA gene sequencing. Perit. Dial. Int. 31:340–346.
    92.
    von Eiff C, Jansen B, Kohnen W, and Becker K. 2005. Infections associated with medical devices: pathogenesis, management and prophylaxis. Drugs 65:179–214.
    93.
    Crass BA and Bergdoll MS. 1986. Involvement of coagulase-negative staphylococci in toxic shock syndrome. J. Clin. Microbiol. 23:43–45.
    94.
    Lina G, Fleer A, Etienne J, Greenland TB, and Vandenesch F. 1996. Coagulase-negative staphylococci isolated from two cases of toxic shock syndrome lack superantigenic activity, but induce cytokine production. FEMS Immunol. Med. Microbiol. 13:81–86.
    95.
    Loïez C, Wallet F, Pischedda P, Renaux E, Senneville E, Mehdi N, and Courcol RJ. 2007. First case of osteomyelitis caused by “Staphylococcus pettenkoferi”. J. Clin. Microbiol. 45:1069–1071.
    96.
    Morfin-Otero R, Martínez-Vázquez MA, López D, Rodríguez-Noriega E, and Garza-González E. 2012. Isolation of rare coagulase-negative isolates in immunocompromised patients: Staphylococcus gallinarum, Staphylococcus pettenkoferi and Staphylococcus pasteuri. Ann. Clin. Lab. Sci. 42:182–185.
    97.
    Peer MA, Nasir RA, Kakru DK, Fomda BA, Bashir G, and Sheikh IA. 2011. Sepsis due to linezolid resistant Staphylococcus cohnii and Staphylococcus kloosii: first reports of linezolid resistance in coagulase negative staphylococci from India. Indian J. Med. Microbiol. 29:60–62.
    98.
    von Eiff C, Peters G, and Heilmann C. 2002. Pathogenesis of infections due to coagulase-negative staphylococci. Lancet Infect. Dis. 2:677–685.
    99.
    Hugonnet S, Sax H, Eggimann P, Chevrolet J-C, and Pittet D. 2004. Nosocomial bloodstream infection and clinical sepsis. Emerg. Infect. Dis. 10:76–81.
    100.
    Sievert DM, Ricks P, Edwards JR, Schneider A, Patel J, Srinivasan A, Kallen A, Limbago B, and Fridkin S. 2013. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009–2010. Infect. Control Hosp. Epidemiol. 34:1–14.
    101.
    Rosenthal VD, Bijie H, Maki DG, Mehta Y, Apisarnthanarak A, Medeiros EA, Leblebicioglu H, Fisher D, Alvarez-Moreno C, Khader IA, Del Rocio Gonzalez MM, Cuellar LE, Navoa-Ng JA, Abouqal R, Guanche GH, Mitrev Z, Pirez Garcia MC, Hamdi A, Duenas L, Cancel E, Gurskis V, Rasslan O, Ahmed A, Kanj SS, Ugalde OC, Mapp T, Raka L, Yuet MC, Thu le TA, Ghazal S, Gikas A, Narvaez LP, Mejia N, Hadjieva N, Gamar Elanbya MO, Guzman Siritt ME, and Jayatilleke K. 2012. International Nosocomial Infection Control Consortium (INICC) report, data summary of 36 countries, for 2004–2009. Am. J. Infect. Control 40:396–407.
    102.
    Hughes JM. 1988. Study on the efficacy of nosocomial infection control (SENIC Project): results and implications for the future. Chemotherapy 34:553–561.
    103.
    McLaws ML and Taylor PC. 2003. The Hospital Infection Standardised Surveillance (HISS) programme: analysis of a two-year pilot. J. Hosp. Infect. 53:259–267.
    104.
    Santucci SG, Gobara S, Santos CR, Fontana C, and Levin AS. 2003. Infections in a burn intensive care unit: experience of seven years. J. Hosp. Infect. 53:6–13.
    105.
    Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, and Edmond MB. 2004. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin. Infect. Dis. 39:309–317.
    106.
    Rello J, Ochagavia A, Sabanes E, Roque M, Mariscal D, Reynaga E, and Valles J. 2000. Evaluation of outcome of intravenous catheter-related infections in critically ill patients. Am. J. Respir. Crit. Care Med. 162:1027–1030.
    107.
    Warren DK, Quadir WW, Hollenbeak CS, Elward AM, Cox MJ, and Fraser VJ. 2006. Attributable cost of catheter-associated bloodstream infections among intensive care patients in a nonteaching hospital. Crit. Care Med. 34:2084–2089.
    108.
    Dimick JB, Pelz RK, Consunji R, Swoboda SM, Hendrix CW, and Lipsett PA. 2001. Increased resource use associated with catheter-related bloodstream infection in the surgical intensive care unit. Arch. Surg. 136:229–234.
    109.
    Blot SI, Depuydt P, Annemans L, Benoit D, Hoste E, De Waele JJ, Decruyenaere J, Vogelaers D, Colardyn F, and Vandewoude KH. 2005. Clinical and economic outcomes in critically ill patients with nosocomial catheter-related bloodstream infections. Clin. Infect. Dis. 41:1591–1598.
    110.
    Leroy O, Meybeck A, Sarraz-Bournet B, d'Elia P, and Legout L. 2012. Vascular graft infections. Curr. Opin. Infect. Dis. 25:154–158.
    111.
    Hill EE, Herijgers P, Herregods MC, and Peetermans WE. 2006. Evolving trends in infective endocarditis. Clin. Microbiol. Infect. 12:5–12.
    112.
    Moreillon P and Que YA. 2004. Infective endocarditis. Lancet 363:139–149.
    113.
    Alonso-Valle H, Fariñas-Alvarez C, García-Palomo JD, Bernal JM, Martín-Duran R, Gutiérrez Díez JF, Revuelta JM, and Fariñas MC. 2010. Clinical course and predictors of death in prosthetic valve endocarditis over a 20-year period. J. Thorac. Cardiovasc. Surg. 139:887–893.
    114.
    Ortega JR, Garcia A, Medina A, and Campoamor C. 2002. Endocarditis protésica precoz de gran agresividad por S. epidermidis [Highly aggressive early prosthetic endocarditis by S. epidermidis]. Rev. Esp. Cardiol. 55:315–318.
    115.
    Karchmer AW, Archer GL, and Dismukes WE. 1983. Staphylococcus epidermidis causing prosthetic valve endocarditis: microbiologic and clinical observations as guides to therapy. Ann. Intern. Med. 98:447–455.
    116.
    Lalani T, Kanafani ZA, Chu VH, Moore L, Corey GR, Pappas P, Woods CW, Cabell CH, Hoen B, Selton-Suty C, Doco-Lecompte T, Chirouze C, Raoult D, Miro JM, Mestres CA, Olaison L, Eykyn S, Abrutyn E, and Fowler VG Jr. 2006. Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database. Eur. J. Clin. Microbiol. Infect. Dis. 25:365–368.
    117.
    Chu VH, Miro JM, Hoen B, Cabell CH, Pappas PA, Jones P, Stryjewski ME, Anguera I, Braun S, Munoz P, Commerford P, Tornos P, Francis J, Oyonarte M, Selton-Suty C, Morris AJ, Habib G, Almirante B, Sexton DJ, Corey GR, and Fowler VG Jr. 2009. Coagulase-negative staphylococcal prosthetic valve endocarditis—a contemporary update based on the International Collaboration on Endocarditis: prospective cohort study. Heart 95:570–576.
    118.
    Falcone M, Campanile F, Giannella M, Borbone S, Stefani S, and Venditti M. 2007. Staphylococcus haemolyticus endocarditis: clinical and microbiologic analysis of 4 cases. Diagn. Microbiol. Infect. Dis. 57:325–331.
    119.
    Cabrera AG, Khan MS, Morales DL, Chen DW, Moffett BS, Price JF, Dreyer WJ, Denfield SW, Jeewa A, Fraser CD Jr, and Vallejo JG. 2013. Infectious complications and outcomes in children supported with left ventricular assist devices. J. Heart Lung Transplant. 32:518–524.
    120.
    Elieson M, Mixon T, and Carpenter J. 2012. Coronary stent infections: a case report and literature review. Tex. Heart Inst. J. 39:884–889.
    121.
    Herrmann M, Weyand M, Greshake B, von Eiff C, Proctor RA, Scheld HH, and Peters G. 1997. Left ventricular assist device infection is associated with increased mortality but is not a contraindication to transplantation. Circulation 95:814–817.
    122.
    Scheithauer S, Bürgel U, Ryang YM, Haase G, Schiefer J, Koch S, Häfner H, and Lemmen S. 2009. Prospective surveillance of drain associated meningitis/ventriculitis in a neurosurgery and neurological intensive care unit. J. Neurol. Neurosurg. Psychiatry 80:1381–1385.
    123.
    Conen A, Walti LN, Merlo A, Fluckiger U, Battegay M, and Trampuz A. 2008. Characteristics and treatment outcome of cerebrospinal fluid shunt-associated infections in adults: a retrospective analysis over an 11-year period. Clin. Infect. Dis. 47:73–82.
    124.
    Davenport A. 2009. Peritonitis remains the major clinical complication of peritoneal dialysis: the London, UK, peritonitis audit 2002–2003. Perit. Dial. Int. 29:297–302.
    125.
    Szeto CC, Kwan BC, Chow KM, Lau MF, Law MC, Chung KY, Leung CB, and Li PK. 2008. Coagulase negative staphylococcal peritonitis in peritoneal dialysis patients: review of 232 consecutive cases. Clin. J. Am. Soc. Nephrol. 3:91–97.
    126.
    Kavanagh D, Prescott GJ, and Mactier RA. 2004. Peritoneal dialysis-associated peritonitis in Scotland (1999-2002). Nephrol. Dial. Transplant. 19:2584–2591.
    127.
    Nessim SJ, Komenda P, Rigatto C, Verrelli M, and Sood MM. 2013. Frequency and microbiology of peritonitis and exit-site infection among obese peritoneal dialysis patients. Perit. Dial. Int. 33:167–174.
    128.
    Zimmerli W, Trampuz A, and Ochsner PE. 2004. Prosthetic-joint infections. N. Engl. J. Med. 351:1645–1654.
    129.
    Peel TN, Cheng AC, Buising KL, and Choong PF. 2012. Microbiological aetiology, epidemiology, and clinical profile of prosthetic joint infections: are current antibiotic prophylaxis guidelines effective? Antimicrob. Agents Chemother. 56:2386–2391.
    130.
    Arciola CR, Campoccia D, An YH, Baldassarri L, Pirini V, Donati ME, Pegreffi F, and Montanaro L. 2006. Prevalence and antibiotic resistance of 15 minor staphylococcal species colonizing orthopedic implants. Int. J. Artif. Organs 29:395–401.
    131.
    Arciola CR, An YH, Campoccia D, Donati ME, and Montanaro L. 2005. Etiology of implant orthopedic infections: a survey on 1027 clinical isolates. Int. J. Artif. Organs 28:1091–1100.
    132.
    Campoccia D, Montanaro L, von Eiff C, Pirini V, Ravaioli S, Becker K, and Arciola CR. 2009. Cluster analysis of ribotyping profiles of Staphylococcus epidermidis isolates recovered from foreign body-associated orthopedic infections. J. Biomed. Mater. Res. A 88:664–672.
    133.
    Coventry MB. 1975. Treatment of infections occurring in total hip surgery. Orthop. Clin. North Am. 6:991–1003.
    134.
    Mavrogenis AF, Papagelopoulos PJ, Coll-Mesa L, Pala E, Guerra G, and Ruggieri P. 2011. Infected tumor prostheses. Orthopedics 34:991–998.
    135.
    Pittet B, Montandon D, and Pittet D. 2005. Infection in breast implants. Lancet Infect. Dis. 5:94–106.
    136.
    Pajkos A, Deva AK, Vickery K, Cope C, Chang L, and Cossart YE. 2003. Detection of subclinical infection in significant breast implant capsules. Plast. Reconstr. Surg. 111:1605–1611.
    137.
    Jansen B, Hartmann C, Schumacher-Perdreau F, and Peters G. 1991. Late onset endophthalmitis associated with intraocular lens: a case of molecularly proved S. epidermidis aetiology. Br. J. Ophthalmol. 75:440–441.
    138.
    Recchia FM, Busbee BG, Pearlman RB, Carvalho-Recchia CA, and Ho AC. 2005. Changing trends in the microbiologic aspects of postcataract endophthalmitis. Arch. Ophthalmol. 123:341–346.
    139.
    Selton-Suty C, Célard M, Le Moing V, Doco-Lecompte T, Chirouze C, Iung B, Strady C, Revest M, Vandenesch F, Bouvet A, Delahaye F, Alla F, Duval X, Hoen B, and AEPEI Study Group. 2012. Preeminence of Staphylococcus aureus in infective endocarditis: a 1-year population-based survey. Clin. Infect. Dis. 54:1230–1239.
    140.
    Quinn EL and Cox F Jr. 1963. Staphylococcus albus (epidermidis) endocarditis: report of 16 cases seen between 1953 and 1962. Antimicrob. Agents Chemother. 161:635–642.
    141.
    Bor DH, Woolhandler S, Nardin R, Brusch J, and Himmelstein DU. 2013. Infective endocarditis in the U.S., 1998–2009: a nationwide study. PLoS One 8:e60033.
    142.
    Castonguay MC, Burner KD, Edwards WD, Baddour LM, and Maleszewski JJ. 2013. Surgical pathology of native valve endocarditis in 310 specimens from 287 patients (1985-2004). Cardiovasc. Pathol. 22:19–27.
    143.
    Ramsey RG, Gunnar RM, and Tobin JR Jr. 1970. Endocarditis in the drug addict. Am. J. Cardiol. 25:608–618.
    144.
    Carozza A, De Santo LS, Romano G, Della CA, Ursomando F, Scardone M, Caianiello G, and Cotrufo M. 2006. Infective endocarditis in intravenous drug abusers: patterns of presentation and long-term outcomes of surgical treatment. J. Heart Valve Dis. 15:125–131.
    145.
    Cunha BA, Esrick MD, and LaRusso M. 2007. Staphylococcus hominis native mitral valve bacterial endocarditis (SBE) in a patient with hypertrophic obstructive cardiomyopathy. Heart Lung 36:380–382.
    146.
    Stöllberger C, Wechsler-Fördös A, Geppert F, Gulz W, Brownstone E, Nicolakis M, and Finsterer J. 2006. Staphylococcus warneri endocarditis after implantation of a lumbar disc prosthesis in an immunocompetent patient. J. Infect. 52:e15–e18.
    147.
    Chu VH, Woods CW, Miro JM, Hoen B, Cabell CH, Pappas PA, Federspiel J, Athan E, Stryjewski ME, Nacinovich F, Marco F, Levine DP, Elliott TS, Fortes CQ, Tornos P, Gordon DL, Utili R, Delahaye F, Corey GR, and Fowler VG Jr. 2008. Emergence of coagulase-negative staphylococci as a cause of native valve endocarditis. Clin. Infect. Dis. 46:232–242.
    148.
    Miele PS, Kogulan PK, Levy CS, Goldstein S, Marcus KA, Smith MA, Rosenthal J, Croxton M, Gill VJ, and Lucey DR. 2001. Seven cases of surgical native valve endocarditis caused by coagulase-negative staphylococci: an underappreciated disease. Am. Heart J. 142:571–576.
    149.
    Etienne J and Eykyn SJ. 1990. Increase in native valve endocarditis caused by coagulase negative staphylococci: an Anglo-French clinical and microbiological study. Br. Heart J. 64:381–384.
    150.
    Caputo GM, Archer GL, Calderwood SB, DiNubile MJ, and Karchmer AW. 1987. Native valve endocarditis due to coagulase-negative staphylococci. Clinical and microbiologic features. Am. J. Med. 83:619–625.
    151.
    Monk AB, Boundy S, Chu VH, Bettinger JC, Robles JR, Fowler VG Jr, and Archer GL. 2008. Analysis of the genotype and virulence of Staphylococcus epidermidis isolates from patients with infective endocarditis. Infect. Immun. 76:5127–5132.
    152.
    Zinkernagel AS, Speck RF, Ruef C, Zingg W, Berger-Bachi B, and Springer B. 2005. Rapidly destructive Staphylococcus epidermidis endocarditis. Infection 33:148–150.
    153.
    Björkqvist M, Liljedahl M, Zimmermann J, Schollin J, and Söderquist B. 2010. Colonization pattern of coagulase-negative staphylococci in preterm neonates and the relation to bacteremia. Eur. J. Clin. Microbiol. Infect. Dis. 29:1085–1093.
    154.
    Hira V, Kornelisse RF, Sluijter M, Kamerbeek A, Goessens WH, de Groot R, and Hermans PW. 2013. Colonization dynamics of antibiotic-resistant coagulase-negative staphylococci in neonates. J. Clin. Microbiol. 51:595–597.
    155.
    Adlerberth I, Lindberg E, Åberg N, Hesselmar B, Saalman R, Strannegård IL, and Wold AE. 2006. Reduced enterobacterial and increased staphylococcal colonization of the infantile bowel: an effect of hygienic lifestyle? Pediatr. Res. 59:96–101.
    156.
    Soeorg H, Huik K, Parm U, Ilmoja ML, Metelskaja N, Metsvaht T, and Lutsar I. 2013. Genetic relatedness of coagulase-negative staphylococci from gastrointestinal tract and blood of preterm neonates with late-onset sepsis. Pediatr. Infect. Dis. J. 32:389–393.
    157.
    Simonsen KA, Anderson-Berry AL, Delair SF, and Davies HD. 2014. Early-onset neonatal sepsis. Clin. Microbiol. Rev. 27:21–47.
    158.
    Stoll BJ and Hansen N. 2003. Infections in VLBW infants: studies from the NICHD Neonatal Research Network. Semin. Perinatol. 27:293–301.
    159.
    Didier C, Streicher MP, Chognot D, Campagni R, Schnebelen A, Messer J, Donato L, Langer B, Meyer N, Astruc D, and Kuhn P. 2012. Late-onset neonatal infections: incidences and pathogens in the era of antenatal antibiotics. Eur. J. Pediatr. 171:681–687.
    160.
    Satar M and Özlü F. 2012. Neonatal sepsis: a continuing disease burden. Turk. J. Pediatr. 54:449–457.
    161.
    Haque KH. 1996. Infection and immunity in the newborn, p 302–310. In Campbell AG and McIntosh N (ed), Forfar & Arneil's textbook of pediatrics, 4th ed. Churchill Livingstone, London, United Kingdom.
    162.
    Thaver D and Zaidi AK. 2009. Burden of neonatal infections in developing countries: a review of evidence from community-based studies. Pediatr. Infect. Dis. J. 28:S3–S9.
    163.
    Healy CM, Palazzi DL, Edwards MS, Campbell JR, and Baker CJ. 2004. Features of invasive staphylococcal disease in neonates. Pediatrics 114:953–961.
    164.
    Munson DP, Thompson TR, Johnson DE, Rhame FS, VanDrunen N, and Ferrieri P. 1982. Coagulase-negative staphylococcal septicemia: experience in a newborn intensive care unit. J. Pediatr. 101:602–605.
    165.
    Battisti O, Mitchison R, and Davies PA. 1981. Changing blood culture isolates in a referral neonatal intensive care unit. Arch. Dis. Child. 56:775–778.
    166.
    Fleer A, Senders RC, Visser MR, Bijlmer RP, Gerards LJ, Kraaijeveld CA, and Verhoef J. 1983. Septicemia due to coagulase-negative staphylococci in a neonatal intensive care unit: clinical and bacteriological features and contaminated parenteral fluids as a source of sepsis. Pediatr. Infect. Dis. 2:426–431.
    167.
    Sgro M, Shah PS, Campbell D, Tenuta A, Shivananda S, and Lee SK. 2011. Early-onset neonatal sepsis: rate and organism pattern between 2003 and 2008. J. Perinatol. 31:794–798.
    168.
    Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, and Poole WK. 2002. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 110:285–291.
    169.
    Freeman J, Epstein MF, Smith NE, Platt R, Sidebottom DG, and Goldmann DA. 1990. Extra hospital stay and antibiotic usage with nosocomial coagulase-negative staphylococcal bacteremia in two neonatal intensive care unit populations. Am. J. Dis. Child. 144:324–329.
    170.
    Khashu M, Osiovich H, Henry D, Al KA, Solimano A, and Speert DP. 2006. Persistent bacteremia and severe thrombocytopenia caused by coagulase-negative Staphylococcus in a neonatal intensive care unit. Pediatrics 117:340–348.
    171.
    Linder N, Hernandez A, Amit L, Klinger G, Ashkenazi S, and Levy I. 2011. Persistent coagulase-negative staphylococci bacteremia in very-low-birth-weight infants. Eur. J. Pediatr. 170:989–995.
    172.
    Yalaz M, Altun-Köroglu O, Ulusoy B, Yildiz B, Akisu M, Vardar F, Özinel MA, and Kültürsay N. 2012. Evaluation of device-associated infections in a neonatal intensive care unit. Turk. J. Pediatr. 54:128–135.
    173.
    Peker E, Kirimi E, Tuncer O, Ceylan A, Cagan E, and Dogan M. 2010. Necrotizing fasciitis caused by Staphylococcus epidermidis in a neonate with extremely low birthweight. J. Dermatol. 37:671–673.
    174.
    Persson E, Trollfors B, Brandberg LL, and Tessin I. 2002. Septicaemia and meningitis in neonates and during early infancy in the Göteborg area of Sweden. Acta Paediatr. 91:1087–1092.
    175.
    Horasan ES, Ersoz G, Tombak A, Tiftik N, and Kaya A. 2011. Bloodstream infections and mortality-related factors in febrile neutropenic cancer patients. Med. Sci. Monit. 17:CR304–CR309.
    176.
    González-Barca E, Fernández-Sevilla A, Carratalá J, Grañena A, and Gudiol F. 1996. Prospective study of 288 episodes of bacteremia in neutropenic cancer patients in a single institution. Eur. J. Clin. Microbiol. Infect. Dis. 15:291–296.
    177.
    Cherif H, Kronvall G, Björkholm M, and Kalin M. 2003. Bacteraemia in hospitalised patients with malignant blood disorders: a retrospective study of causative agents and their resistance profiles during a 14-year period without antibacterial prophylaxis. Hematol. J. 4:420–426.
    178.
    Rubio M, Palau L, Vivas JR, del Potro E, Diaz-Mediavilla J, Alvarez A, Martinez R, and Picazo JJ. 1994. Predominance of gram-positive microorganisms as a cause of septicemia in patients with hematological malignancies. Infect. Control Hosp. Epidemiol. 15:101–104.
    179.
    Coullioud D, van der Auwera P, Viot M, and Lasset C. 1993. Prospective multicentric study of the etiology of 1051 bacteremic episodes in 782 cancer patients. CEMIC (French-Belgian Study Club of Infectious Diseases in Cancer). Support Care Cancer 1:34–46.
    180.
    Escande MC and Herbrecht R. 1998. Prospective study of bacteraemia in cancer patients. Results of a French multicentre study. Support Care Cancer 6:273–280.
    181.
    Muldrew KL, Tang YW, Li H, and Stratton CW. 2008. Clonal dissemination of Staphylococcus epidermidis in an oncology ward. J. Clin. Microbiol. 46:3391–3396.
    182.
    Müller-Premru M and Cernelc P. 2004. Molecular epidemiology of catheter-related bloodstream infections caused by coagulase-negative staphylococci in haematological patients with neutropenia. Epidemiol. Infect. 132:921–925.
    183.
    Frank KL, Del Pozo JL, and Patel R. 2008. From clinical microbiology to infection pathogenesis: how daring to be different works for Staphylococcus lugdunensis. Clin. Microbiol. Rev. 21:111–133.
    184.
    Etienne J, Pangon B, Leport C, Wolff M, Clair B, Perronne C, Brun Y, and Buré A. 1989. Staphylococcus lugdunensis endocarditis. Lancet 333:390.
    185.
    Fleurette J, Bès M, Brun Y, Freney J, Forey F, Coulet M, Reverdy ME, and Etienne J. 1989. Clinical isolates of Staphylococcus lugdunensis and S. schleiferi: bacteriological characteristics and susceptibility to antimicrobial agents. Res. Microbiol. 140:107–118.
    186.
    Anguera I, Del Río A, Miró JM, Matínez-Lacasa X, Marco F, Gumá JR, Quaglio G, Claramonte X, Moreno A, Mestres CA, Mauri E, Azqueta M, Benito N, García-de la Maria C, Almela M, Jiménez-Expósito MJ, Sued O, De Lazzari E, and Gatell JM. 2005. Staphylococcus lugdunensis infective endocarditis: description of 10 cases and analysis of native valve, prosthetic valve, and pacemaker lead endocarditis clinical profiles. Heart 91:e10.
    187.
    Liang M, Mansell C, Wade C, Fisher R, and Devlin G. 2012. Unusually virulent coagulase-negative Staphylococcus lugdunensis is frequently associated with infective endocarditis: a Waikato series of patients. N. Z. Med. J. 125:51–59.
    188.
    Vandenesch F, Etienne J, Reverdy ME, and Eykyn SJ. 1993. Endocarditis due to Staphylococcus lugdunensis: report of 11 cases and review. Clin. Infect. Dis. 17:871–876.
    189.
    Liu PY, Huang YF, Tang CW, Chen YY, Hsieh KS, Ger LP, Chen YS, and Liu YC. 2010. Staphylococcus lugdunensis infective endocarditis: a literature review and analysis of risk factors. J. Microbiol. Immunol. Infect. 43:478–484.
    190.
    Seifert H, Oltmanns D, Becker K, Wisplinghoff H, and von Eiff C. 2005. Staphylococcus lugdunensis pacemaker-related infection. Emerg. Infect. Dis. 11:1283–1286.
    191.
    Li YM, Blaskiewicz DJ, and Hall WA. 2013. Shunt-related intracranial abscess caused by Staphylococcus lugdunensis in a hydranencephalic patient. World Neurosurg. 80:e387–e389.
    192.
    Elliott SP, Yogev R, and Shulman ST. 2001. Staphylococcus lugdunensis: an emerging cause of ventriculoperitoneal shunt infections. Pediatr. Neurosurg. 35:128–130.
    193.
    Sampathkumar P, Osmon DR, and Cockerill FR III. 2000. Prosthetic joint infection due to Staphylococcus lugdunensis. Mayo Clin. Proc. 75:511–512.
    194.
    Kaabia N, Scauarda D, Lena G, and Drancourt M. 2002. Molecular identification of Staphylococcus lugdunensis in a patient with meningitis. J. Clin. Microbiol. 40:1824–1825.
    195.
    Koch LD, Knoll F, Hartmann G, and Lhotta K. 2011. Recurrent exit-site infection due to Staphylococcus lugdunensis—a virulent coagulase-negative Staphylococcus. Perit. Dial. Int. 31:372–373.
    196.
    Zinkernagel AS, Zinkernagel MS, Elzi MV, Genoni M, Gubler J, Zbinden R, and Mueller NJ. 2008. Significance of Staphylococcus lugdunensis bacteremia: report of 28 cases and review of the literature. Infection 36:314–321.
    197.
    Choi SH, Chung JW, Lee EJ, Kim TH, Lee MS, Kang JM, Song EH, Jun JB, Kim MN, Kim YS, Woo JH, and Choi SH. 2010. Incidence, characteristics, and outcomes of Staphylococcus lugdunensis bacteremia. J. Clin. Microbiol. 48:3346–3349.
    198.
    Hung T, Zaghi S, Yousefzadeh J, and Leibowitz M. 2012. Necrotizing fasciitis associated with Staphylococcus lugdunensis. Case Rep. Infect. Dis. 2012:453685.
    199.
    Böcher S, Tønning B, Skov RL, and Prag J. 2009. Staphylococcus lugdunensis, a common cause of skin and soft tissue infections in the community. J. Clin. Microbiol. 47:946–950.
    200.
    Arias M, Tena D, Apellaniz M, Asensio MP, Caballero P, Hernandez C, Tejedor F, and Bisquert J. 2010. Skin and soft tissue infections caused by Staphylococcus lugdunensis: report of 20 cases. Scand. J. Infect. Dis. 42:879–884.
    201.
    Papapetropoulos N, Papapetropoulou M, and Vantarakis A. 2013. Abscesses and wound infections due to Staphylococcus lugdunensis: report of 16 cases. Infection 41:525–528.
    202.
    Hubiche T, Del Giudice P, and Roudière L. 2009. Staphylococcus lugdunensis in skin infections: pathogen or colonizing bacterium? J. Clin. Microbiol. 47:3057.
    203.
    Bellamy R and Barkham T. 2002. Staphylococcus lugdunensis infection sites: predominance of abscesses in the pelvic girdle region. Clin. Infect. Dis. 35:E32–E34.
    204.
    Ros MJ, Ramirez A, Arteaga E, Alberto C, Gil J, and Reina J. 1999. Infección por Staphylococcus lugdunensis: caracterización clinicomicrobiológica de 25 casos. Enferm. Infecc. Microbiol. Clin. 17:223–226.
    205.
    Bello C, Eskandar M, El GR, Sobande A, Nour H, and Shafiq H. 2007. Staphylococcus lugdunensis endometritis: a case report. West Afr. J. Med. 26:243–245.
    206.
    Shaaban HS, Choo HF, and Sensakovic JW. 2011. A case of Staphylococcus lugdunensis related pyomyoma occurring after Cesarean section. J. Glob. Infect. Dis. 3:101–102.
    207.
    Greig JM and Wood MJ. 2003. Staphylococcus lugdunensis vertebral osteomyelitis. Clin. Microbiol. Infect. 9:1139–1141.
    208.
    Cooke RP, James SE, and Sallomi DF. 2003. Infective discitis due to Staphylococcus lugdunensis—a case of missed opportunity. Br. J. Biomed. Sci. 60:162–164.
    209.
    Palazzo E, Pierre J, and Besbes N. 1992. Staphylococcus lugdunensis arthritis: a complication of arthroscopy. J. Rheumatol. 19:327–328.
    210.
    Grupper M, Potasman I, Rosner I, Slobodin G, and Rozenbaum M. 2010. Septic arthritis due to Staphylococcus lugdunensis in a native joint. Rheumatol. Int. 30:1231–1233.
    211.
    Latham RH, Running K, and Stamm WE. 1983. Urinary tract infections in young adult women caused by Staphylococcus saprophyticus. JAMA 250:3063–3066.
    212.
    Raz R, Colodner R, and Kunin CM. 2005. Who are you—Staphylococcus saprophyticus? Clin. Infect. Dis. 40:896–898.
    213.
    Hovelius B and Mårdh PA. 1984. Staphylococcus saprophyticus as a common cause of urinary tract infections. Rev. Infect. Dis. 6:328–337.
    214.
    Choi SH, Woo JH, Jeong JY, Kim NJ, Kim MN, Kim YS, and Ryu J. 2006. Clinical significance of Staphylococcus saprophyticus identified on blood culture in a tertiary care hospital. Diagn. Microbiol. Infect. Dis. 56:337–339.
    215.
    Garduño E, Márquez I, Beteta A, Said I, Blanco J, and Pineda T. 2005. Staphylococcus saprophyticus causing native valve endocarditis. Scand. J. Infect. Dis. 37:690–691.
    216.
    Proctor RA, von Eiff C, Kahl BC, Becker K, McNamara P, Herrmann M, and Peters G. 2006. Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat. Rev. Microbiol. 4:295–305.
    217.
    Baddour LM and Christensen GD. 1987. Prosthetic valve endocarditis due to small-colony staphylococcal variants. Rev. Infect. Dis. 9:1168–1174.
    218.
    Borderon E and Horodniceanu T. 1976. Mutants déficients a colonies naines de Staphylococcus: étude de trois souches isolées chez des malades porteurs d′ostéosynthèses. Ann. Microbiol. (Paris) 127:503–514.
    219.
    von Eiff C, Vaudaux P, Kahl BC, Lew D, Emler S, Schmidt A, Peters G, and Proctor RA. 1999. Bloodstream infections caused by small-colony variants of coagulase-negative staphylococci following pacemaker implantation. Clin. Infect. Dis. 29:932–934.
    220.
    Baddour LM, Barker LP, Christensen GD, Parisi JT, and Simpson WA. 1990. Phenotypic variation of Staphylococcus epidermidis in infection of transvenous endocardial pacemaker electrodes. J. Clin. Microbiol. 28:676–679.
    221.
    Adler H, Widmer A, and Frei R. 2003. Emergence of a teicoplanin-resistant small colony variant of Staphylococcus epidermidis during vancomycin therapy. Eur. J. Clin. Microbiol. Infect. Dis. 22:746–748.
    222.
    Al Laham N, Rohde H, Sander G, Fischer A, Hussain M, Heilmann C, Mack D, Proctor R, Peters G, Becker K, and von Eiff C. 2007. Augmented expression of polysaccharide intercellular adhesin in a defined Staphylococcus epidermidis mutant with the small-colony-variant phenotype. J. Bacteriol. 189:4494–4501.
    223.
    Sander G, Börner T, Kriegeskorte A, von Eiff C, Becker K, and Mahabir E. 2012. Catheter colonization and abscess formation due to Staphylococcus epidermidis with normal and small-colony-variant phenotype is mouse strain dependent. PLoS One 7:e36602.
    224.
    Peters G, Locci R, and Pulverer G. 1982. Adherence and growth of coagulase-negative staphylococci on surfaces of intravenous catheters. J. Infect. Dis. 146:479–482.
    225.
    Christensen GD, Simpson WA, Bisno AL, and Beachey EH. 1982. Adherence of slime-producing strains of Staphylococcus epidermidis to smooth surfaces. Infect. Immun. 37:318–326.
    226.
    Peters G, Locci R, and Pulverer G. 1981. Microbial colonization of prosthetic devices. II. Scanning electron microscopy of naturally infected intravenous catheters. Zentralbl. Bakteriol. Mikrobiol. Hyg. B 173:293–299.
    227.
    Hussain M, Wilcox MH, and White PJ. 1993. The slime of coagulase-negative staphylococci: biochemistry and relation to adherence. FEMS Microbiol. Rev. 10:191–207.
    228.
    Mack D, Fischer W, Krokotsch A, Leopold K, Hartmann R, Egge H, and Laufs R. 1996. The intercellular adhesin involved in biofilm accumulation of Staphylococcus epidermidis is a linear beta-1,6-linked glucosaminoglycan: purification and structural analysis. J. Bacteriol. 178:175–183.
    229.
    Rohde H, Burdelski C, Bartscht K, Hussain M, Buck F, Horstkotte MA, Knobloch JK, Heilmann C, Herrmann M, and Mack D. 2005. Induction of Staphylococcus epidermidis biofilm formation via proteolytic processing of the accumulation-associated protein by staphylococcal and host proteases. Mol. Microbiol. 55:1883–1895.
    230.
    Sadovskaya I, Vinogradov E, Flahaut S, Kogan G, and Jabbouri S. 2005. Extracellular carbohydrate-containing polymers of a model biofilm-producing strain, Staphylococcus epidermidis RP62A. Infect. Immun. 73:3007–3017.
    231.
    Schommer NN, Christner M, Hentschke M, Ruckdeschel K, Aepfelbacher M, and Rohde H. 2011. Staphylococcus epidermidis uses distinct mechanisms of biofilm formation to interfere with phagocytosis and activation of mouse macrophage-like cells 774A.1. Infect. Immun. 79:2267–2276.
    232.
    Izano EA, Amarante MA, Kher WB, and Kaplan JB. 2008. Differential roles of poly-N-acetylglucosamine surface polysaccharide and extracellular DNA in Staphylococcus aureus and Staphylococcus epidermidis biofilms. Appl. Environ. Microbiol. 74:470–476.
    233.
    Heilmann C. 2011. Adhesion mechanisms of staphylococci. Adv. Exp. Med. Biol. 715:105–123.
    234.
    Clarke SR and Foster SJ. 2006. Surface adhesins of Staphylococcus aureus. Adv. Microb. Physiol. 51:187–224.
    235.
    Patti JM, Allen BL, McGavin MJ, and Höök M. 1994. MSCRAMM-mediated adherence of microorganisms to host tissues. Annu. Rev. Microbiol. 48:585–617.
    236.
    Chavakis T, Wiechmann K, Preissner KT, and Herrmann M. 2005. Staphylococcus aureus interactions with the endothelium: the role of bacterial “secretable expanded repertoire adhesive molecules” (SERAM) in disturbing host defense systems. Thromb. Haemost. 94:278–285.
    237.
    Foster TJ, Geoghegan JA, Ganesh VK, and Höök M. 2014. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat. Rev. Microbiol. 12:49–62.
    238.
    Costerton JW, Stewart PS, and Greenberg EP. 1999. Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322.
    239.
    Heilmann C, Hussain M, Peters G, and Götz F. 1997. Evidence for autolysin-mediated primary attachment of Staphylococcus epidermidis to a polystyrene surface. Mol. Microbiol. 24:1013–1024.
    240.
    Hirschhausen N, Schlesier T, Peters G, and Heilmann C. 2012. Characterization of the modular design of the autolysin/adhesin Aaa from Staphylococcus aureus. PLoS One 7:e40353.
    241.
    Biswas R, Voggu L, Simon UK, Hentschel P, Thumm G, and Götz F. 2006. Activity of the major staphylococcal autolysin Atl. FEMS Microbiol. Lett. 259:260–268.
    242.
    Schlag M, Biswas R, Krismer B, Kohler T, Zoll S, Yu W, Schwarz H, Peschel A, and Gotz F. 2010. Role of staphylococcal wall teichoic acid in targeting the major autolysin Atl. Mol. Microbiol. 75:864–873.
    243.
    Allignet J, Aubert S, Dyke KG, and El Solh N. 2001. Staphylococcus caprae strains carry determinants known to be involved in pathogenicity: a gene encoding an autolysin-binding fibronectin and the ica operon involved in biofilm formation. Infect. Immun. 69:712–718.
    244.
    Hell W, Meyer HG, and Gatermann SG. 1998. Cloning of aas, a gene encoding a Staphylococcus saprophyticus surface protein with adhesive and autolytic properties. Mol. Microbiol. 29:871–881.
    245.
    Yokoi KJ, Sugahara K, Iguchi A, Nishitani G, Ikeda M, Shimada T, Inagaki N, Yamakawa A, Taketo A, and Kodaira K. 2008. Molecular properties of the putative autolysin Atl(WM) encoded by Staphylococcus warneri M: mutational and biochemical analyses of the amidase and glucosaminidase domains. Gene 416:66–76.
    246.
    Bourgeois I, Camiade E, Biswas R, Courtin P, Gibert L, Götz F, Chapot-Chartier MP, Pons JL, and Pestel-Caron M. 2009. Characterization of AtlL, a bifunctional autolysin of Staphylococcus lugdunensis with N-acetylglucosaminidase and N-acetylmuramoyl-l-alanine amidase activities. FEMS Microbiol. Lett. 290:105–113.
    247.
    Qin Z, Ou Y, Yang L, Zhu Y, Tolker-Nielsen T, Molin S, and Qu D. 2007. Role of autolysin-mediated DNA release in biofilm formation of Staphylococcus epidermidis. Microbiology 153:2083–2092.
    248.
    Bose JL, Lehman MK, Fey PD, and Bayles KW. 2012. Contribution of the Staphylococcus aureus Atl AM and GL murein hydrolase activities in cell division, autolysis, and biofilm formation. PLoS One 7:e42244.
    249.
    Zoll S, Pätzold B, Schlag M, Götz F, Kalbacher H, and Stehle T. 2010. Structural basis of cell wall cleavage by a staphylococcal autolysin. PLoS Pathog. 6:e1000807.
    250.
    Zoll S, Schlag M, Shkumatov AV, Rautenberg M, Svergun DI, Götz F, and Stehle T. 2012. Ligand-binding properties and conformational dynamics of autolysin repeat domains in staphylococcal cell wall recognition. J. Bacteriol. 194:3789–3802.
    251.
    Wang C, Li M, Dong D, Wang J, Ren J, Otto M, and Gao Q. 2007. Role of ClpP in biofilm formation and virulence of Staphylococcus epidermidis. Microbes Infect. 9:1376–1383.
    252.
    Cucarella C, Solano C, Valle J, Amorena B, Lasa I, and Penadés JR. 2001. Bap, a Staphylococcus aureus surface protein involved in biofilm formation. J. Bacteriol. 183:2888–2896.
    253.
    Tormo MA, Knecht E, Götz F, Lasa I, and Penadés JR. 2005. Bap-dependent biofilm formation by pathogenic species of Staphylococcus: evidence of horizontal gene transfer? Microbiology 151:2465–2475.
    254.
    Potter A, Ceotto H, Giambiagi-deMarval M, dos Santos KR, Nes IF, and do Carmo de Freire Bastos M. 2009. The gene bap, involved in biofilm production, is present in Staphylococcus spp. strains from nosocomial infections. J. Microbiol. 47:319–326.
    255.
    Sadovskaya I, Vinogradov E, Li J, and Jabbouri S. 2004. Structural elucidation of the extracellular and cell-wall teichoic acids of Staphylococcus epidermidis RP62A, a reference biofilm-positive strain. Carbohydr. Res. 339:1467–1473.
    256.
    Gross M, Cramton SE, Götz F, and Peschel A. 2001. Key role of teichoic acid net charge in Staphylococcus aureus colonization of artificial surfaces. Infect. Immun. 69:3423–3426.
    257.
    Holland LM, Conlon B, and O'Gara JP. 2011. Mutation of tagO reveals an essential role for wall teichoic acids in Staphylococcus epidermidis biofilm development. Microbiology 157:408–418.
    258.
    Herrmann M, Lai QJ, Albrecht RM, Mosher DF, and Proctor RA. 1993. Adhesion of Staphylococcus aureus to surface-bound platelets: role of fibrinogen/fibrin and platelet integrins. J. Infect. Dis. 167:312–322.
    259.
    Herrmann M, Hartleib J, Kehrel B, Montgomery RR, Sixma JJ, and Peters G. 1997. Interaction of von Willebrand factor with Staphylococcus aureus. J. Infect. Dis. 176:984–991.
    260.
    Rupp ME, Fey PD, Heilmann C, and Götz F. 2001. Characterization of the importance of Staphylococcus epidermidis autolysin and polysaccharide intercellular adhesin in the pathogenesis of intravascular catheter-associated infection in a rat model. J. Infect. Dis. 183:1038–1042.
    261.
    Allignet J, England P, Old I, and El Solh N. 2002. Several regions of the repeat domain of the Staphylococcus caprae autolysin, AtlC, are involved in fibronectin binding. FEMS Microbiol. Lett. 213:193–197.
    262.
    Heilmann C, Thumm G, Chhatwal GS, Hartleib J, Uekötter A, and Peters G. 2003. Identification and characterization of a novel autolysin (Aae) with adhesive properties from Staphylococcus epidermidis. Microbiology 149:2769–2778.
    263.
    Buist G, Steen A, Kok J, and Kuipers OP. 2008. LysM, a widely distributed protein motif for binding to (peptido)glycans. Mol. Microbiol. 68:838–847.
    264.
    Zou Y and Hou C. 2010. Systematic analysis of an amidase domain CHAP in 12 Staphylococcus aureus genomes and 44 staphylococcal phage genomes. Comput. Biol. Chem. 34:251–257.
    265.
    Bowden MG, Visai L, Longshaw CM, Holland KT, Speziale P, and Höök M. 2002. Is the GehD lipase from Staphylococcus epidermidis a collagen binding adhesin? J. Biol. Chem. 277:43017–43023.
    266.
    Gill SR, Fouts DE, Archer GL, Mongodin EF, Deboy RT, Ravel J, Paulsen IT, Kolonay JF, Brinkac L, Beanan M, Dodson RJ, Daugherty SC, Madupu R, Angiuoli SV, Durkin AS, Haft DH, Vamathevan J, Khouri H, Utterback T, Lee C, Dimitrov G, Jiang L, Qin H, Weidman J, Tran K, Kang K, Hance IR, Nelson KE, and Fraser CM. 2005. Insights on evolution of virulence and resistance from the complete genome analysis of an early methicillin-resistant Staphylococcus aureus strain and a biofilm-producing methicillin-resistant Staphylococcus epidermidis strain. J. Bacteriol. 187:2426–2438.
    267.
    Christner M, Franke GC, Schommer NN, Wendt U, Wegert K, Pehle P, Kroll G, Schulze C, Buck F, Mack D, Aepfelbacher M, and Rohde H. 2010. The giant extracellular matrix-binding protein of Staphylococcus epidermidis mediates biofilm accumulation and attachment to fibronectin. Mol. Microbiol. 75:187–207.
    268.
    Williams RJ, Henderson B, Sharp LJ, and Nair SP. 2002. Identification of a fibronectin-binding protein from Staphylococcus epidermidis. Infect. Immun. 70:6805–6810.
    269.
    Schneewind O, Mihaylova-Petkov D, and Model P. 1993. Cell wall sorting signals in surface proteins of gram-positive bacteria. EMBO J. 12:4803–4811.
    270.
    Mazmanian SK, Liu G, Ton-That H, and Schneewind O. 1999. Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall. Science 285:760–763.
    271.
    Bowden MG, Chen W, Singvall J, Xu Y, Peacock SJ, Valtulina V, Speziale P, and Höök M. 2005. Identification and preliminary characterization of cell-wall-anchored proteins of Staphylococcus epidermidis. Microbiology 151:1453–1464.
    272.
    Nilsson M, Frykberg L, Flock JI, Pei L, Lindberg M, and Guss B. 1998. A fibrinogen-binding protein of Staphylococcus epidermidis. Infect. Immun. 66:2666–2673.
    273.
    Pei L, Palma M, Nilsson M, Guss B, and Flock JI. 1999. Functional studies of a fibrinogen binding protein from Staphylococcus epidermidis. Infect. Immun. 67:4525–4530.
    274.
    Pei L and Flock JI. 2001. Lack of fbe, the gene for a fibrinogen-binding protein from Staphylococcus epidermidis, reduces its adherence to fibrinogen coated surfaces. Microb. Pathog. 31:185–193.
    275.
    Hartford O, O'Brien L, Schofield K, Wells J, and Foster TJ. 2001. The Fbe (SdrG) protein of Staphylococcus epidermidis HB promotes bacterial adherence to fibrinogen. Microbiology 147:2545–2552.
    276.
    Guo B, Zhao X, Shi Y, Zhu D, and Zhang Y. 2007. Pathogenic implication of a fibrinogen-binding protein of Staphylococcus epidermidis in a rat model of intravascular-catheter-associated infection. Infect. Immun. 75:2991–2995.
    277.
    Brennan MP, Loughman A, Devocelle M, Arasu S, Chubb AJ, Foster TJ, and Cox D. 2009. Elucidating the role of Staphylococcus epidermidis serine-aspartate repeat protein G in platelet activation. J. Thromb. Haemost. 7:1364–1372.
    278.
    Davis SL, Gurusiddappa S, McCrea KW, Perkins S, and Höök M. 2001. SdrG, a fibrinogen-binding bacterial adhesin of the microbial surface components recognizing adhesive matrix molecules subfamily from Staphylococcus epidermidis, targets the thrombin cleavage site in the Bβ chain. J. Biol. Chem. 276:27799–27805.
    279.
    Ponnuraj K, Bowden MG, Davis S, Gurusiddappa S, Moore D, Choe D, Xu Y, Hook M, and Narayana SV. 2003. A “dock, lock, and latch” structural model for a staphylococcal adhesin binding to fibrinogen. Cell 115:217–228.
    280.
    McCrea KW, Hartford O, Davis S, Eidhin DN, Lina G, Speziale P, Foster TJ, and Höök M. 2000. The serine-aspartate repeat (Sdr) protein family in Staphylococcus epidermidis. Microbiology 146:1535–1546.
    281.
    Arrecubieta C, Lee MH, Macey A, Foster TJ, and Lowy FD. 2007. SdrF, a Staphylococcus epidermidis surface protein, binds type I collagen. J. Biol. Chem. 282:18767–18776.
    282.
    Shahrooei M, Hira V, Stijlemans B, Merckx R, Hermans PW, and Van EJ. 2009. Inhibition of Staphylococcus epidermidis biofilm formation by rabbit polyclonal antibodies against the SesC protein. Infect. Immun. 77:3670–3678.
    283.
    Shahrooei M, Hira V, Khodaparast L, Khodaparast L, Stijlemans B, Kucharikova S, Burghout P, Hermans PW, and Van Eldere J. 2012. Vaccination with SesC decreases Staphylococcus epidermidis biofilm formation. Infect. Immun. 80:3660–3668.
    284.
    Macintosh RL, Brittan JL, Bhattacharya R, Jenkinson HF, Derrick J, Upton M, and Handley PS. 2009. The terminal A domain of the fibrillar accumulation-associated protein (Aap) of Staphylococcus epidermidis mediates adhesion to human corneocytes. J. Bacteriol. 191:7007–7016.
    285.
    Hussain M, Heilmann C, Peters G, and Herrmann M. 2001. Teichoic acid enhances adhesion of Staphylococcus epidermidis to immobilized fibronectin. Microb. Pathog. 31:261–270.
    286.
    McKenney D, Hübner J, Muller E, Wang Y, Goldmann DA, and Pier GB. 1998. The ica locus of Staphylococcus epidermidis encodes production of the capsular polysaccharide/adhesin. Infect. Immun. 66:4711–4720.
    287.
    Mack D, Nedelmann M, Krokotsch A, Schwarzkopf A, Heesemann J, and Laufs R. 1994. Characterization of transposon mutants of biofilm-producing Staphylococcus epidermidis impaired in the accumulative phase of biofilm production: genetic identification of a hexosamine-containing polysaccharide intercellular adhesin. Infect. Immun. 62:3244–3253.
    288.
    Cramton SE, Gerke C, Schnell NF, Nichols WW, and Götz F. 1999. The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation. Infect. Immun. 67:5427–5433.
    289.
    McKenney D, Pouliot KL, Wang Y, Murthy V, Ulrich M, Döring G, Lee JC, Goldmann DA, and Pier GB. 1999. Broadly protective vaccine for Staphylococcus aureus based on an in vivo-expressed antigen. Science 284:1523–1527.
    290.
    Maira-Litran T, Kropec A, Abeygunawardana C, Joyce J, Mark G, Goldmann DA III, and Pier GB. 2002. Immunochemical properties of the staphylococcal poly-N-acetylglucosamine surface polysaccharide. Infect. Immun. 70:4433–4440.
    291.
    Vuong C, Kocianova S, Voyich JM, Yao Y, Fischer ER, DeLeo FR, and Otto M. 2004. A crucial role for exopolysaccharide modification in bacterial biofilm formation, immune evasion, and virulence. J. Biol. Chem. 279:54881–54886.
    292.
    Kaplan JB, Velliyagounder K, Ragunath C, Rohde H, Mack D, Knobloch JK, and Ramasubbu N. 2004. Genes involved in the synthesis and degradation of matrix polysaccharide in Actinobacillus actinomycetemcomitans and Actinobacillus pleuropneumoniae biofilms. J. Bacteriol. 186:8213–8220.
    293.
    Gerke C, Kraft A, Süssmuth R, Schweitzer O, and Götz F. 1998. Characterization of the N-acetylglucosaminyltransferase activity involved in the biosynthesis of the Staphylococcus epidermidis polysaccharide intercellular adhesin. J. Biol. Chem. 273:18586–18593.
    294.
    Heilmann C, Schweitzer O, Gerke C, Vanittanakom N, Mack D, and Götz F. 1996. Molecular basis of intercellular adhesion in the biofilm-forming Staphylococcus epidermidis. Mol. Microbiol. 20:1083–1091.
    295.
    Rupp ME, Ulphani JS, Fey PD, Bartscht K, and Mack D. 1999. Characterization of the importance of polysaccharide intercellular adhesin/hemagglutinin of Staphylococcus epidermidis in the pathogenesis of biomaterial-based infection in a mouse foreign body infection model. Infect. Immun. 67:2627–2632.
    296.
    Rupp ME, Ulphani JS, Fey PD, and Mack D. 1999. Characterization of Staphylococcus epidermidis polysaccharide intercellular adhesin/hemagglutinin in the pathogenesis of intravascular catheter-associated infection in a rat model. Infect. Immun. 67:2656–2659.
    297.
    Ziebuhr W, Heilmann C, Götz F, Meyer P, Wilms K, Straube E, and Hacker J. 1997. Detection of the intercellular adhesion gene cluster (ica) and phase variation in Staphylococcus epidermidis blood culture strains and mucosal isolates. Infect. Immun. 65:890–896.
    298.
    Frank KL and Patel R. 2007. Poly-N-acetylglucosamine is not a major component of the extracellular matrix in biofilms formed by icaADBC-positive Staphylococcus lugdunensis isolates. Infect. Immun. 75:4728–4742.
    299.
    Chokr A, Watier D, Eleaume H, Pangon B, Ghnassia JC, Mack D, and Jabbouri S. 2006. Correlation between biofilm formation and production of polysaccharide intercellular adhesin in clinical isolates of coagulase-negative staphylococci. Int. J. Med. Microbiol. 296:381–388.
    300.
    Hussain M, Herrmann M, von Eiff C, Perdreau-Remington F, and Peters G. 1997. A 140-kilodalton extracellular protein is essential for the accumulation of Staphylococcus epidermidis strains on surfaces. Infect. Immun. 65:519–524.
    301.
    Schumacher-Perdreau F, Heilmann C, Peters G, Götz F, and Pulverer G. 1994. Comparative analysis of a biofilm-forming Staphylococcus epidermidis strain and its adhesion-positive, accumulation-negative mutant M7. FEMS Microbiol. Lett. 117:71–78.
    302.
    Rohde H, Kalitzky M, Kroger N, Scherpe S, Horstkotte MA, Knobloch JK, Zander AR, and Mack D. 2004. Detection of virulence-associated genes not useful for discriminating between invasive and commensal Staphylococcus epidermidis strains from a bone marrow transplant unit. J. Clin. Microbiol. 42:5614–5619.
    303.
    Vandecasteele SJ, Peetermans WE, Merckx R, Rijnders BJ, and Van EJ. 2003. Reliability of the ica, aap and atlE genes in the discrimination between invasive, colonizing and contaminant Staphylococcus epidermidis isolates in the diagnosis of catheter-related infections. Clin. Microbiol. Infect. 9:114–119.
    304.
    Conrady DG, Brescia CC, Horii K, Weiss AA, Hassett DJ, and Herr AB. 2008. A zinc-dependent adhesion module is responsible for intercellular adhesion in staphylococcal biofilms. Proc. Natl. Acad. Sci. U. S. A. 105:19456–19461.
    305.
    Bateman A, Holden MT, and Yeats C. 2005. The G5 domain: a potential N-acetylglucosamine recognition domain involved in biofilm formation. Bioinformatics 21:1301–1303.
    306.
    Banner MA, Cunniffe JG, Macintosh RL, Foster TJ, Rohde H, Mack D, Hoyes E, Derrick J, Upton M, and Handley PS. 2007. Localized tufts of fibrils on Staphylococcus epidermidis NCTC 11047 are comprised of the accumulation-associated protein. J. Bacteriol. 189:2793–2804.
    307.
    Conrady DG, Wilson JJ, and Herr AB. 2013. Structural basis for Zn2+-dependent intercellular adhesion in staphylococcal biofilms. Proc. Natl. Acad. Sci. U. S. A. 110:E202–E211.
    308.
    Sun D, Accavitti MA, and Bryers JD. 2005. Inhibition of biofilm formation by monoclonal antibodies against Staphylococcus epidermidis RP62A accumulation-associated protein. Clin. Diagn. Lab. Immunol. 12:93–100.
    309.
    Itoh Y, Wang X, Hinnebusch BJ, Preston JF III, and Romeo T. 2005. Depolymerization of β-1,6-N-acetyl-d-glucosamine disrupts the integrity of diverse bacterial biofilms. J. Bacteriol. 187:382–387.
    310.
    Rice KC, Mann EE, Endres JL, Weiss EC, Cassat JE, Smeltzer MS, and Bayles KW. 2007. The cidA murein hydrolase regulator contributes to DNA release and biofilm development in Staphylococcus aureus. Proc. Natl. Acad. Sci. U. S. A. 104:8113–8118.
    311.
    Kiedrowski MR, Kavanaugh JS, Malone CL, Mootz JM, Voyich JM, Smeltzer MS, Bayles KW, and Horswill AR. 2011. Nuclease modulates biofilm formation in community-associated methicillin-resistant Staphylococcus aureus. PLoS One 6:e26714.
    312.
    Hu Y, Meng J, Shi C, Hervin K, Fratamico PM, and Shi X. 2013. Characterization and comparative analysis of a second thermonuclease from Staphylococcus aureus. Microbiol. Res. 168:174–182.
    313.
    Beenken KE, Spencer H, Griffin LM, and Smeltzer MS. 2012. Impact of extracellular nuclease production on the biofilm phenotype of Staphylococcus aureus under in vitro and in vivo conditions. Infect. Immun. 80:1634–1638.
    314.
    Kogan G, Sadovskaya I, Chaignon P, Chokr A, and Jabbouri S. 2006. Biofilms of clinical strains of Staphylococcus that do not contain polysaccharide intercellular adhesin. FEMS Microbiol. Lett. 255:11–16.
    315.
    Rohde H, Burandt EC, Siemssen N, Frommelt L, Burdelski C, Wurster S, Scherpe S, Davies AP, Harris LG, Horstkotte MA, Knobloch JK, Ragunath C, Kaplan JB, and Mack D. 2007. Polysaccharide intercellular adhesin or protein factors in biofilm accumulation of Staphylococcus epidermidis and Staphylococcus aureus isolated from prosthetic hip and knee joint infections. Biomaterials 28:1711–1720.
    316.
    Heidrich C, Hantke K, Bierbaum G, and Sahl HG. 1996. Identification and analysis of a gene encoding a Fur-like protein of Staphylococcus epidermidis. FEMS Microbiol. Lett. 140:253–259.
    317.
    Chaignon P, Sadovskaya I, Ragunah C, Ramasubbu N, Kaplan JB, and Jabbouri S. 2007. Susceptibility of staphylococcal biofilms to enzymatic treatments depends on their chemical composition. Appl. Microbiol. Biotechnol. 75:125–132.
    318.
    Boles BR and Horswill AR. 2008. agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog. 4:e1000052.
    319.
    Dubin G, Chmiel D, Mak P, Rakwalska M, Rzychon M, and Dubin A. 2001. Molecular cloning and biochemical characterisation of proteases from Staphylococcus epidermidis. Biol. Chem. 382:1575–1582.
    320.
    Moon JL, Banbula A, Oleksy A, Mayo JA, and Travis J. 2001. Isolation and characterization of a highly specific serine endopeptidase from an oral strain of Staphylococcus epidermidis. Biol. Chem. 382:1095–1099.
    321.
    Ohara-Nemoto Y, Ikeda Y, Kobayashi M, Sasaki M, Tajika S, and Kimura S. 2002. Characterization and molecular cloning of a glutamyl endopeptidase from Staphylococcus epidermidis. Microb. Pathog. 33:33–41.
    322.
    Sugimoto S, Iwamoto T, Takada K, Okuda K, Tajima A, Iwase T, and Mizunoe Y. 2013. Staphylococcus epidermidis Esp degrades specific proteins associated with Staphylococcus aureus biofilm formation and host-pathogen interaction. J. Bacteriol. 195:1645–1655.
    323.
    Chen C, Krishnan V, Macon K, Manne K, Narayana SV, and Schneewind O. 2013. Secreted proteases control autolysin-mediated biofilm growth of Staphylococcus aureus. J. Biol. Chem. 288:29440–29452.
    324.
    Geissler S, Götz F, and Kupke T. 1996. Serine protease EpiP from Staphylococcus epidermidis catalyzes the processing of the epidermin precursor peptide. J. Bacteriol. 178:284–288.
    325.
    Cockayne A, Hill PJ, Powell NB, Bishop K, Sims C, and Williams P. 1998. Molecular cloning of a 32-kilodalton lipoprotein component of a novel iron-regulated Staphylococcus epidermidis ABC transporter. Infect. Immun. 66:3767–3774.
    326.
    Teufel P and Götz F. 1993. Characterization of an extracellular metalloprotease with elastase activity from Staphylococcus epidermidis. J. Bacteriol. 175:4218–4224.
    327.
    Lai Y, Villaruz AE, Li M, Cha DJ, Sturdevant DE, and Otto M. 2007. The human anionic antimicrobial peptide dermcidin induces proteolytic defence mechanisms in staphylococci. Mol. Microbiol. 63:497–506.
    328.
    Oleksy A, Golonka E, Banbula A, Szmyd G, Moon J, Kubica M, Greenbaum D, Bogyo M, Foster TJ, Travis J, and Potempa J. 2004. Growth phase-dependent production of a cell wall-associated elastinolytic cysteine proteinase by Staphylococcus epidermidis. Biol. Chem. 385:525–535.
    329.
    Vuong C, Gerke C, Somerville GA, Fischer ER, and Otto M. 2003. Quorum-sensing control of biofilm factors in Staphylococcus epidermidis. J. Infect. Dis. 188:706–718.
    330.
    Mehlin C, Headley CM, and Klebanoff SJ. 1999. An inflammatory polypeptide complex from Staphylococcus epidermidis: isolation and characterization. J. Exp. Med. 189:907–918.
    331.
    Cheung GY, Rigby K, Wang R, Queck SY, Braughton KR, Whitney AR, Teintze M, DeLeo FR, and Otto M. 2010. Staphylococcus epidermidis strategies to avoid killing by human neutrophils. PLoS Pathog. 6:e1001133.
    332.
    McKevitt AI, Bjornson GL, Mauracher CA, and Scheifele DW. 1990. Amino acid sequence of a deltalike toxin from Staphylococcus epidermidis. Infect. Immun. 58:1473–1475.
    333.
    Queck SY, Khan BA, Wang R, Bach TH, Kretschmer D, Chen L, Kreiswirth BN, Peschel A, DeLeo FR, and Otto M. 2009. Mobile genetic element-encoded cytolysin connects virulence to methicillin resistance in MRSA. PLoS Pathog. 5:e1000533.
    334.
    Vuong C, Saenz HL, Götz F, and Otto M. 2000. Impact of the agr quorum-sensing system on adherence to polystyrene in Staphylococcus aureus. J. Infect. Dis. 182:1688–1693.
    335.
    Yao Y, Sturdevant DE, and Otto M. 2005. Genomewide analysis of gene expression in Staphylococcus epidermidis biofilms: insights into the pathophysiology of S. epidermidis biofilms and the role of phenol-soluble modulins in formation of biofilms. J. Infect. Dis. 191:289–298.
    336.
    Wang R, Khan BA, Cheung GY, Bach TH, Jameson-Lee M, Kong KF, Queck SY, and Otto M. 2011. Staphylococcus epidermidis surfactant peptides promote biofilm maturation and dissemination of biofilm-associated infection in mice. J. Clin. Invest. 121:238–248.
    337.
    Hirschhausen N, Schlesier T, Schmidt MA, Götz F, Peters G, and Heilmann C. 2010. A novel staphylococcal internalization mechanism involves the major autolysin Atl and heat shock cognate protein Hsc70 as host cell receptor. Cell. Microbiol. 12:1746–1764.
    338.
    Khalil H, Williams RJ, Stenbeck G, Henderson B, Meghji S, and Nair SP. 2007. Invasion of bone cells by Staphylococcus epidermidis. Microbes Infect. 9:460–465.
    339.
    Valour F, Trouillet-Assant S, Rasigade JP, Lustig S, Chanard E, Meugnier H, Tigaud S, Vandenesch F, Etienne J, Ferry T, and Laurent F. 2013. Staphylococcus epidermidis in orthopedic device infections: the role of bacterial internalization in human osteoblasts and biofilm formation. PLoS One 8:e67240.
    340.
    Szabados F, Kleine B, Anders A, Kaase M, Sakinç T, Schmitz I, and Gatermann S. 2008. Staphylococcus saprophyticus ATCC 15305 is internalized into human urinary bladder carcinoma cell line 5637. FEMS Microbiol. Lett. 285:163–169.
    341.
    Kriegeskorte A, König S, Sander G, Pirkl A, Mahabir E, Proctor RA, von Eiff C, Peters G, and Becker K. 2011. Small colony variants of Staphylococcus aureus reveal distinct protein profiles. Proteomics 11:2476–2490.
    342.
    von Eiff C, McNamara P, Becker K, Bates D, Lei XH, Ziman M, Bochner BR, Peters G, and Proctor RA. 2006. Phenotype microarray profiling of Staphylococcus aureus menD and hemB mutants with the small-colony-variant phenotype. J. Bacteriol. 188:687–693.
    343.
    Seggewiss J, Becker K, Kotte O, Eisenacher M, Khoschkhoi Yazdi MR, Fischer A, McNamara P, Al Laham N, Proctor R, Peters G, Heinemann M, and von Eiff C. 2006. Reporter metabolite analysis of transcriptional profiles of a Staphylococcus aureus strain with normal phenotype and its isogenic hemB mutant displaying the small-colony-variant phenotype. J. Bacteriol. 188:7765–7777.
    344.
    Besier S, Ludwig A, Ohlsen K, Brade V, and Wichelhaus TA. 2007. Molecular analysis of the thymidine-auxotrophic small colony variant phenotype of Staphylococcus aureus. Int. J. Med. Microbiol. 297:217–225.
    345.
    Chatterjee I, Kriegeskorte A, Fischer A, Deiwick S, Theimann N, Proctor RA, Peters G, Herrmann M, and Kahl BC. 2008. In vivo mutations of thymidylate synthase (encoded by thyA) are responsible for thymidine dependency in clinical small-colony variants of Staphylococcus aureus. J. Bacteriol. 190:834–842.
    346.
    Lannergård J, von Eiff C, Sander G, Cordes T, Seggewiss J, Peters G, Proctor RA, Becker K, and Hughes D. 2008. Identification of the genetic basis for clinical menadione-auxotrophic small-colony variant isolates of Staphylococcus aureus. Antimicrob. Agents Chemother. 52:4017–4022.
    347.
    von Eiff C, Heilmann C, Proctor RA, Woltz C, Peters G, and Götz F. 1997. A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly. J. Bacteriol. 179:4706–4712.
    348.
    Abu-Qatouseh LF, Chinni SV, Seggewiss J, Proctor RA, Brosius J, Rozhdestvensky TS, Peters G, von Eiff C, and Becker K. 2010. Identification of differentially expressed small non-protein-coding RNAs in Staphylococcus aureus displaying both the normal and the small-colony variant phenotype. J. Mol. Med. 88:565–575.
    349.
    Tuchscherr L, Heitmann V, Hussain M, Viemann D, Roth J, von Eiff C, Peters G, Becker K, and Löffler B. 2010. Staphylococcus aureus small-colony variants are adapted phenotypes for intracellular persistence. J. Infect. Dis. 202:1031–1040.
    350.
    Tuchscherr L, Medina E, Hussain M, Völker W, Heitmann V, Niemann S, Holzinger D, Roth J, Proctor RA, Becker K, Peters G, and Löffler B. 2011. Staphylococcus aureus phenotype switching: an effective bacterial strategy to escape host immune response and establish a chronic infection. EMBO Mol. Med. 3:129–141.
    351.
    von Eiff C, Becker K, Metze D, Lubritz G, Hockmann J, Schwarz T, and Peters G. 2001. Intracellular persistence of Staphylococcus aureus small-colony variants within keratinocytes: a cause for antibiotic treatment failure in a patient with Darier's disease. Clin. Infect. Dis. 32:1643–1647.
    352.
    Mattsson E, Verhage L, Rollof J, Fleer A, Verhoef J, and van Dijk H. 1993. Peptidoglycan and teichoic acid from Staphylococcus epidermidis stimulate human monocytes to release tumour necrosis factor-α, interleukin-1 β and interleukin-6. FEMS Immunol. Med. Microbiol. 7:281–287.
    353.
    Mattsson E, Rollof J, Verhoef J, van Dijk H, and Fleer A. 1994. Serum-induced potentiation of tumor necrosis factor alpha production by human monocytes in response to staphylococcal peptidoglycan: involvement of different serum factors. Infect. Immun. 62:3837–3843.
    354.
    Kristian SA, Birkenstock TA, Sauder U, Mack D, Götz F, and Landmann R. 2008. Biofilm formation induces C3a release and protects Staphylococcus epidermidis from IgG and complement deposition and from neutrophil-dependent killing. J. Infect. Dis. 197:1028–1035.
    355.
    Johnson GM, Lee DA, Regelmann WE, Gray ED, Peters G, and Quie PG. 1986. Interference with granulocyte function by Staphylococcus epidermidis slime. Infect. Immun. 54:13–20.
    356.
    Begun J, Gaiani JM, Rohde H, Mack D, Calderwood SB, Ausubel FM, and Sifri CD. 2007. Staphylococcal biofilm exopolysaccharide protects against Caenorhabditis elegans immune defenses. PLoS Pathog. 3:e57.
    357.
    Rennermalm A, Nilsson M, and Flock JI. 2004. The fibrinogen binding protein of Staphylococcus epidermidis is a target for opsonic antibodies. Infect. Immun. 72:3081–3083.
    358.
    Farrell AM, Foster TJ, and Holland KT. 1993. Molecular analysis and expression of the lipase of Staphylococcus epidermidis. J. Gen. Microbiol. 139:267–277.
    359.
    Simons JW, van Kampen MD, Riel S, Götz F, Egmond MR, and Verheij HM. 1998. Cloning, purification and characterisation of the lipase from Staphylococcus epidermidis—comparison of the substrate selectivity with those of other microbial lipases. Eur. J. Biochem. 253:675–683.
    360.
    Longshaw CM, Farrell AM, Wright JD, and Holland KT. 2000. Identification of a second lipase gene, gehD, in Staphylococcus epidermidis: comparison of sequence with those of other staphylococcal lipases. Microbiology 146:1419–1427.
    361.
    Liles WC, Thomsen AR, O'Mahony DS, and Klebanoff SJ. 2001. Stimulation of human neutrophils and monocytes by staphylococcal phenol-soluble modulin. J. Leukoc. Biol. 70:96–102.
    362.
    Vuong C, Dürr M, Carmody AB, Peschel A, Klebanoff SJ, and Otto M. 2004. Regulated expression of pathogen-associated molecular pattern molecules in Staphylococcus epidermidis: quorum-sensing determines pro-inflammatory capacity and production of phenol-soluble modulins. Cell. Microbiol. 6:753–759.
    363.
    Scheifele DW, Bjornson GL, Dyer RA, and Dimmick JE. 1987. Delta-like toxin produced by coagulase-negative staphylococci is associated with neonatal necrotizing enterocolitis. Infect. Immun. 55:2268–2273.
    364.
    Kahler RC, Boyce JM, Bergdoll MS, Lockwood WR, and Taylor MR. 1986. Toxic shock syndrome associated with TSST-1 producing coagulase-negative staphylococci. Am. J. Med. Sci. 292:310–312.
    365.
    Kreiswirth BN, Schlievert PM, and Novick RP. 1987. Evaluation of coagulase-negative staphylococci for ability to produce toxic shock syndrome toxin 1. J. Clin. Microbiol. 25:2028–2029.
    366.
    Becker K, Haverkämper G, von Eiff C, Roth R, and Peters G. 2001. Survey of staphylococcal enterotoxin genes, exfoliative toxin genes, and toxic shock syndrome toxin 1 gene in non-Staphylococcus aureus species. Eur. J. Clin. Microbiol. Infect. Dis. 20:407–409.
    367.
    Blaiotta G, Ercolini D, Pennacchia C, Fusco V, Casaburi A, Pepe O, and Villani F. 2004. PCR detection of staphylococcal enterotoxin genes in Staphylococcus spp. strains isolated from meat and dairy products. Evidence for new variants of seG and seI in S. aureus AB-8802. J. Appl. Microbiol. 97:719–730.
    368.
    Spaulding AR, Salgado-Pabón W, Kohler PL, Horswill AR, Leung DY, and Schlievert PM. 2013. Staphylococcal and streptococcal superantigen exotoxins. Clin. Microbiol. Rev. 26:422–447.
    369.
    Madhusoodanan J, Seo KS, Remortel B, Park JY, Hwang SY, Fox LK, Park YH, Deobald CF, Wang D, Liu S, Daugherty SC, Gill AL, Bohach GA, and Gill SR. 2011. An enterotoxin-bearing pathogenicity island in Staphylococcus epidermidis. J. Bacteriol. 193:1854–1862.
    370.
    Valle J, Vadillo S, Piriz S, and Gomez-Lucia E. 1991. Toxic shock syndrome toxin 1 (TSST-1) production by staphylococci isolated from goats and presence of specific antibodies to TSST-1 in serum and milk. Appl. Environ. Microbiol. 57:889–891.
    371.
    Park JY, Fox LK, Seo KS, McGuire MA, Park YH, Rurangirwa FR, Sischo WM, and Bohach GA. 2011. Detection of classical and newly described staphylococcal superantigen genes in coagulase-negative staphylococci isolated from bovine intramammary infections. Vet. Microbiol. 147:149–154.
    372.
    Rosec JP, Guiraud JP, Dalet C, and Richard N. 1997. Enterotoxin production by staphylococci isolated from foods in France. Int. J. Food Microbiol. 35:213–221.
    373.
    Nemati M, Hermans K, Vancraeynest D, De Vliegher S, Sampimon OC, Baele M, De Graef EM, Pasmans F, and Haesebrouck F. 2008. Screening of bovine coagulase-negative staphylococci from milk for superantigen-encoding genes. Vet. Rec. 163:740–743.
    374.
    Götz F, Perconti S, Popella P, Werner R, and Schlag M. 2014. Epidermin and gallidermin: staphylococcal lantibiotics. Int. J. Med. Microbiol. 304:63–71.
    375.
    Sahl HG and Bierbaum G. 1998. Lantibiotics: biosynthesis and biological activities of uniquely modified peptides from gram-positive bacteria. Annu. Rev. Microbiol. 52:41–79.
    376.
    Novick RP. 2003. Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol. Microbiol. 48:1429–1449.
    377.
    Dufour P, Jarraud S, Vandenesch F, Greenland T, Novick RP, Bes M, Etienne J, and Lina G. 2002. High genetic variability of the agr locus in Staphylococcus species. J. Bacteriol. 184:1180–1186.
    378.
    Xu L, Li H, Vuong C, Vadyvaloo V, Wang J, Yao Y, Otto M, and Gao Q. 2006. Role of the luxS quorum-sensing system in biofilm formation and virulence of Staphylococcus epidermidis. Infect. Immun. 74:488–496.
    379.
    Novick RP and Geisinger E. 2008. Quorum sensing in staphylococci. Annu. Rev. Genet. 42:541–564.
    380.
    Otto M, Süssmuth R, Vuong C, Jung G, and Götz F. 1999. Inhibition of virulence factor expression in Staphylococcus aureus by the Staphylococcus epidermidis agr pheromone and derivatives. FEBS Lett. 450:257–262.
    381.
    van Wamel WJ, van Rossum G, Verhoef J, Vandenbroucke-Grauls CM, and Fluit AC. 1998. Cloning and characterization of an accessory gene regulator (agr)-like locus from Staphylococcus epidermidis. FEMS Microbiol. Lett. 163:1–9.
    382.
    Otto M, Süssmuth R, Jung G, and Götz F. 1998. Structure of the pheromone peptide of the Staphylococcus epidermidis agr system. FEBS Lett. 424:89–94.
    383.
    Vuong C, Götz F, and Otto M. 2000. Construction and characterization of an agr deletion mutant of Staphylococcus epidermidis. Infect. Immun. 68:1048–1053.
    384.
    Vuong C, Kocianova S, Yao Y, Carmody AB, and Otto M. 2004. Increased colonization of indwelling medical devices by quorum-sensing mutants of Staphylococcus epidermidis in vivo. J. Infect. Dis. 190:1498–1505.
    385.
    Yarwood JM, Bartels DJ, Volper EM, and Greenberg EP. 2004. Quorum sensing in Staphylococcus aureus biofilms. J. Bacteriol. 186:1838–1850.
    386.
    Doherty N, Holden MT, Qazi SN, Williams P, and Winzer K. 2006. Functional analysis of luxS in Staphylococcus aureus reveals a role in metabolism but not quorum sensing. J. Bacteriol. 188:2885–2897.
    387.
    Fluckiger U, Wolz C, and Cheung AL. 1998. Characterization of a sar homolog of Staphylococcus epidermidis. Infect. Immun. 66:2871–2878.
    388.
    Tormo MA, Marti M, Valle J, Manna AC, Cheung AL, Lasa I, and Penades JR. 2005. SarA is an essential positive regulator of Staphylococcus epidermidis biofilm development. J. Bacteriol. 187:2348–2356.
    389.
    Handke LD, Slater SR, Conlon KM, O'Donnell ST, Olson ME, Bryant KA, Rupp ME, O'Gara JP, and Fey PD. 2007. SigmaB and SarA independently regulate polysaccharide intercellular adhesin production in Staphylococcus epidermidis. Can. J. Microbiol. 53:82–91.
    390.
    Christner M, Heinze C, Busch M, Franke G, Hentschke M, Bayard Dühring S, Büttner H, Kotasinska M, Wischnewski V, Kroll G, Buck F, Molin S, Otto M, and Rohde H. 2012. sarA negatively regulates Staphylococcus epidermidis biofilm formation by modulating expression of 1 MDa extracellular matrix binding protein and autolysis-dependent release of eDNA. Mol. Microbiol. 86:394–410.
    391.
    Wang L, Li M, Dong D, Bach TH, Sturdevant DE, Vuong C, Otto M, and Gao Q. 2008. SarZ is a key regulator of biofilm formation and virulence in Staphylococcus epidermidis. J. Infect. Dis. 197:1254–1262.
    392.
    Rowe SE, Mahon V, Smith SG, and O'Gara JP. 2011. A novel role for SarX in Staphylococcus epidermidis biofilm regulation. Microbiology 157:1042–1049.
    393.
    Kies S, Otto M, Vuong C, and Götz F. 2001. Identification of the sigB operon in Staphylococcus epidermidis: construction and characterization of a sigB deletion mutant. Infect. Immun. 69:7933–7936.
    394.
    Knobloch JK, Bartscht K, Sabottke A, Rohde H, Feucht HH, and Mack D. 2001. Biofilm formation by Staphylococcus epidermidis depends on functional RsbU, an activator of the sigB operon: differential activation mechanisms due to ethanol and salt stress. J. Bacteriol. 183:2624–2633.
    395.
    Conlon KM, Humphreys H, and O'Gara JP. 2002. icaR encodes a transcriptional repressor involved in environmental regulation of ica operon expression and biofilm formation in Staphylococcus epidermidis. J. Bacteriol. 184:4400–4408.
    396.
    Becker K and von Eiff C. 2011. Staphylococcus, Micrococcus, and other catalase-positive cocci, p 308–330. In Versalovic J, Carroll KC, Funke G, Jorgensen JH, Landry ML, and Warnock DW (ed), Manual of clinical microbiology, 10th ed. ASM Press, Washington, DC.
    397.
    Winn WC Jr, Allen SD, Janda WM, Koneman EW, Procop GW, Schreckenberger PC, and Woods GL. 2006. Koneman's color atlas and textbook of diagnostic microbiology. Lippincott, Philadelphia, PA.
    398.
    Garcia LS. 2010. Clinical microbiology procedures handbook, 3rd ed. ASM Press, Washington, DC.
    399.
    Maki DG, Weise CE, and Sarafin HW. 1977. A semiquantitative culture method for identifying intravenous-catheter-related infection. N. Engl. J. Med. 296:1305–1309.
    400.
    Blot F, Nitenberg G, Chachaty E, Raynard B, Germann N, Antoun S, Laplanche A, Brun-Buisson C, and Tancrède C. 1999. Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures. Lancet 354:1071–1077.
    401.
    Raad I, Hanna HA, Alakech B, Chatzinikolaou I, Johnson MM, and Tarrand J. 2004. Differential time to positivity: a useful method for diagnosing catheter-related bloodstream infections. Ann. Intern. Med. 140:18–25.
    402.
    Safdar N, Fine JP, and Maki DG. 2005. Meta-analysis: methods for diagnosing intravascular device-related bloodstream infection. Ann. Intern. Med. 142:451–466.
    403.
    Trampuz A, Piper KE, Jacobson MJ, Hanssen AD, Unni KK, Osmon DR, Mandrekar JN, Cockerill FR, Steckelberg JM, Greenleaf JF, and Patel R. 2007. Sonication of removed hip and knee prostheses for diagnosis of infection. N. Engl. J. Med. 357:654–663.
    404.
    Rieger UM, Pierer G, Lüscher NJ, and Trampuz A. 2009. Sonication of removed breast implants for improved detection of subclinical infection. Aesthetic Plast. Surg. 33:404–408.
    405.
    Rohacek M, Weisser M, Kobza R, Schoenenberger AW, Pfyffer GE, Frei R, Erne P, and Trampuz A. 2010. Bacterial colonization and infection of electrophysiological cardiac devices detected with sonication and swab culture. Circulation 121:1691–1697.
    406.
    Sampedro MF, Huddleston PM, Piper KE, Karau MJ, Dekutoski MB, Yaszemski MJ, Currier BL, Mandrekar JN, Osmon DR, McDowell A, Patrick S, Steckelberg JM, and Patel R. 2010. A biofilm approach to detect bacteria on removed spinal implants. Spine 35:1218–1224.
    407.
    Kloos WE and Schleifer KH. 1975. Simplified scheme for routine identification of human Staphylococcus species. J. Clin. Microbiol. 1:82–88.
    408.
    Becker K, Laham NA, Fegeler W, Proctor RA, Peters G, and von Eiff C. 2006. Fourier-transform infrared spectroscopic analysis is a powerful tool for studying the dynamic changes in Staphylococcus aureus small-colony variants. J. Clin. Microbiol. 44:3274–3278.
    409.
    van Griethuysen A, Bes M, Etienne J, Zbinden R, and Kluytmans J. 2001. International multicenter evaluation of latex agglutination tests for identification of Staphylococcus aureus. J. Clin. Microbiol. 39:86–89.
    410.
    Personne P, Bes M, Lina G, Vandenesch F, Brun Y, and Etienne J. 1997. Comparative performances of six agglutination kits assessed by using typical and atypical strains of Staphylococcus aureus. J. Clin. Microbiol. 35:1138–1140.
    411.
    Fournier JM, Bouvet A, Mathieu D, Nato F, Boutonnier A, Gerbal R, Brunengo P, Saulnier C, Sagot N, and Slizewicz B. 1993. New latex reagent using monoclonal antibodies to capsular polysaccharide for reliable identification of both oxacillin-susceptible and oxacillin-resistant Staphylococcus aureus. J. Clin. Microbiol. 31:1342–1344.
    412.
    Blake JE and Metcalfe MA. 2001. A shared noncapsular antigen is responsible for false-positive reactions by Staphylococcus epidermidis in commercial agglutination tests for Staphylococcus aureus. J. Clin. Microbiol. 39:544–550.
    413.
    Poutrel B, Mendolia C, Sutra L, and Fournier JM. 1990. Reactivity of coagulase-negative staphylococci isolated from cow and goat milk with monoclonal antibodies to Staphylococcus aureus capsular polysaccharide types 5 and 8. J. Clin. Microbiol. 28:358–360.
    414.
    Meyer HG, Muthing J, and Gatermann SG. 1997. The hemagglutinin of Staphylococcus saprophyticus binds to a protein receptor on sheep erythrocytes. Med. Microbiol. Immunol. (Berl.) 186:37–43.
    415.
    Hébert GA, Crowder CG, Hancock GA, Jarvis WR, and Thornsberry C. 1988. Characteristics of coagulase-negative staphylococci that help differentiate these species and other members of the family Micrococcaceae. J. Clin. Microbiol. 26:1939–1949.
    416.
    Bannerman TL, Kleeman KT, and Kloos W. 1993. Evaluation of the Vitek systems Gram-positive identification card for species identification of coagulase-negative staphylococci. J. Clin. Microbiol. 31:1322–1325.
    417.
    Ieven MJ, Verhoeven SR, Pattyn SR, and Goossens H. 1995. Rapid and economical method for species identification of clinically significant coagulase-negative staphylococci. J. Clin. Microbiol. 33:1060–1063.
    418.
    Kellogg JA, Hanna MD, Nelsen SJ, Sprenkle LS, Thomas ML, and Young KS. 1996. Predictive values of species identification from the Vitek Gram-positive identification card using clinical isolates of coagulase-negative staphylococci. Am. J. Clin. Pathol. 106:374–377.
    419.
    Renneberg J, Rieneck K, and Gutschik E. 1995. Evaluation of Staph ID 32 system and Staph-Zym system for identification of coagulase-negative staphylococci. J. Clin. Microbiol. 33:1150–1153.
    420.
    Olendzki AN, Barros EM, Laport MS, dos Santos KR, and Giambiagi-deMarval M. 2014. Reliability of the MicroScan WalkAway PC21 panel in identifying and detecting oxacillin resistance in clinical coagulase-negative staphylococci strains. Eur. J. Clin. Microbiol. Infect. Dis. 33:29–33.
    421.
    Zadoks RN and Watts JL. 2009. Species identification of coagulase-negative staphylococci: genotyping is superior to phenotyping. Vet. Microbiol. 134:20–28.
    422.
    Becker K, Harmsen D, Mellmann A, Meier C, Schumann P, Peters G, and von Eiff C. 2004. Development and evaluation of a quality-controlled ribosomal sequence database for 16S ribosomal DNA-based identification of Staphylococcus species. J. Clin. Microbiol. 42:4988–4995.
    423.
    Sethi S, Nanda R, and Chakraborty T. 2013. Clinical application of volatile organic compound analysis for detecting infectious diseases. Clin. Microbiol. Rev. 26:462–475.
    424.
    Niederbracht Y, Idelevich EA, Penner H, Berdel WE, Peters G, Silling G, and Becker K. 2013. Applicability of a commercial multiplex PCR test for identification of true blood stream infections with coagulase-negative staphylococci in neutropenic hematological patients. Int. J. Med. Microbiol. 303:13.
    425.
    Straub JA, Hertel C, and Hammes WP. 1999. A 23S rDNA-targeted polymerase chain reaction-based system for detection of Staphylococcus aureus in meat starter cultures and dairy products. J. Food Prot. 62:1150–1156.
    426.
    Edwards KJ, Kaufmann ME, and Saunders NA. 2001. Rapid and accurate identification of coagulase-negative staphylococci by real-time PCR. J. Clin. Microbiol. 39:3047–3051.
    427.
    Mendoza M, Meugnier H, Bes M, Etienne J, and Freney J. 1998. Identification of Staphylococcus species by 16S-23S rDNA intergenic spacer PCR analysis. Int. J. Syst. Bacteriol. 48:1049–1055.
    428.
    Goh SH, Santucci Z, Kloos WE, Faltyn M, George CG, Driedger D, and Hemmingsen SM. 1997. Identification of Staphylococcus species and subspecies by the chaperonin 60 gene identification method and reverse checkerboard hybridization. J. Clin. Microbiol. 35:3116–3121.
    429.
    Goh SH, Potter S, Wood JO, Hemmingsen SM, Reynolds RP, and Chow AW. 1996. HSP60 gene sequences as universal targets for microbial species identification: studies with coagulase-negative staphylococci. J. Clin. Microbiol. 34:818–823.
    430.
    Martineau F, Picard FJ, Ke D, Paradis S, Roy PH, Ouellette M, and Bergeron MG. 2001. Development of a PCR assay for identification of staphylococci at genus and species levels. J. Clin. Microbiol. 39:2541–2547.
    431.
    Poyart C, Quesne G, Boumaila C, and Trieu-Cuot P. 2001. Rapid and accurate species-level identification of coagulase-negative staphylococci by using the sodA gene as a target. J. Clin. Microbiol. 39:4296–4301.
    432.
    Mellmann A, Becker K, von Eiff C, Keckevoet U, Schumann P, and Harmsen D. 2006. Sequencing and staphylococci identification. Emerg. Infect. Dis. 12:333–336.
    433.
    Monecke S and Ehricht R. 2005. Rapid genotyping of methicillin-resistant Staphylococcus aureus (MRSA) isolates using miniaturised oligonucleotide arrays. Clin. Microbiol. Infect. 11:825–833.
    434.
    Frye JG, Jesse T, Long F, Rondeau G, Porwollik S, McClelland M, Jackson CR, Englen M, and Fedorka-Cray PJ. 2006. DNA microarray detection of antimicrobial resistance genes in diverse bacteria. Int. J. Antimicrob. Agents 27:138–151.
    435.
    Hensley DM, Tapia R, and Encina Y. 2009. An evaluation of the AdvanDx Staphylococcus aureus/CNS PNA FISH™ assay. Clin. Lab. Sci. 22:30–33.
    436.
    Amiali NM, Mulvey MR, Sedman J, Louie M, Simor AE, and Ismail AA. 2007. Rapid identification of coagulase-negative staphylococci by Fourier transform infrared spectroscopy. J. Microbiol. Methods 68:236–242.
    437.
    Clark AE, Kaleta EJ, Arora A, and Wolk DM. 2013. Matrix-assisted laser desorption ionization–time of flight mass spectrometry: a fundamental shift in the routine practice of clinical microbiology. Clin. Microbiol. Rev. 26:547–603.
    438.
    Carbonnelle E, Beretti JL, Cottyn S, Quesne G, Berche P, Nassif X, and Ferroni A. 2007. Rapid identification of staphylococci isolated in clinical microbiology laboratories by matrix-assisted laser desorption ionization–time of flight mass spectrometry. J. Clin. Microbiol. 45:2156–2161.
    439.
    Dubois D, Leyssene D, Chacornac JP, Kostrzewa M, Schmit PO, Talon R, Bonnet R, and Delmas J. 2010. Identification of a variety of Staphylococcus species by matrix-assisted laser desorption ionization–time of flight mass spectrometry. J. Clin. Microbiol. 48:941–945.
    440.
    Wolk DM, Blyn LB, Hall TA, Sampath R, Ranken R, Ivy C, Melton R, Matthews H, White N, Li F, Harpin V, Ecker DJ, Limbago B, McDougal LK, Wysocki VH, Cai M, and Carroll KC. 2009. Pathogen profiling: rapid molecular characterization of Staphylococcus aureus by PCR/electrospray ionization-mass spectrometry and correlation with phenotype. J. Clin. Microbiol. 47:3129–3137.
    441.
    Souvenir D, Anderson DE Jr, Palpant S, Mroch H, Askin S, Anderson J, Claridge J, Eiland J, Malone C, Garrison MW, Watson P, and Campbell DM. 1998. Blood cultures positive for coagulase-negative staphylococci: antisepsis, pseudobacteremia, and therapy of patients. J. Clin. Microbiol. 36:1923–1926.
    442.
    Hall KK and Lyman JA. 2006. Updated review of blood culture contamination. Clin. Microbiol. Rev. 19:788–802.
    443.
    Tokars JI. 2004. Predictive value of blood cultures positive for coagulase-negative staphylococci: implications for patient care and health care quality assurance. Clin. Infect. Dis. 39:333–341.
    444.
    Beekmann SE, Diekema DJ, and Doern GV. 2005. Determining the clinical significance of coagulase-negative staphylococci isolated from blood cultures. Infect. Control Hosp. Epidemiol. 26:559–566.
    445.
    Favre B, Hugonnet S, Correa L, Sax H, Rohner P, and Pittet D. 2005. Nosocomial bacteremia: clinical significance of a single blood culture positive for coagulase-negative staphylococci. Infect. Control Hosp. Epidemiol. 26:697–702.
    446.
    García-Vázquez E, Fernández-Rufete A, Hernández-Torres A, Canteras M, Ruiz J, and Gómez J. 2013. When is coagulase-negative Staphylococcus bacteraemia clinically significant? Scand. J. Infect. Dis. 45:664–671.
    447.
    Kresken M and Hafner D. 1999. Drug resistance among clinical isolates of frequently encountered bacterial species in central Europe during 1975–1995. Infection 27(Suppl 2):S2–S8.
    448.
    Andrews J, Ashby J, Jevons G, Marshall T, Lines N, and Wise R. 2000. A comparison of antimicrobial resistance rates in Gram-positive pathogens isolated in the UK from October 1996 to January 1997 and October 1997 to January 1998. J. Antimicrob. Chemother. 45:285–293.
    449.
    Lyytikäinen O, Vaara M, Järviluoma E, Rosenqvist K, Tiittanen L, and Valtonen V. 1996. Increased resistance among Staphylococcus epidermidis isolates in a large teaching hospital over a 12-year period. Eur. J. Clin. Microbiol. Infect. Dis. 15:133–138.
    450.
    European Committee on Antimicrobial Susceptibility Testing. 2013. Breakpoint tables for interpretation of MICs and zone diameters, version 3.1. http://www.eucast.org.
    451.
    Clinical and Laboratory Standards Institute (CLSI). 2013. Performance standards for antimicrobial susceptibility testing; 23rd informational supplement. M100-S23. CLSI, Wayne, PA.
    452.
    Griffith GC and Levinson DC. 1949. Subacute bacterial endocarditis; a report on 57 patients treated with massive doses of penicillin. Calif. Med. 71:403–408.
    453.
    Kirby WM. 1944. Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci. Science 99:452–453.
    454.
    Cherifi S, Byl B, Deplano A, Nonhoff C, Denis O, and Hallin M. 2013. Comparative epidemiology of Staphylococcus epidermidis isolates from patients with catheter-related bacteremia and from healthy volunteers. J. Clin. Microbiol. 51:1541–1547.
    455.
    Hartman BJ and Tomasz A. 1984. Low-affinity penicillin-binding protein associated with beta-lactam resistance in Staphylococcus aureus. J. Bacteriol. 158:513–516.
    456.
    Kjellander JO, Klein JO, and Finland M. 1963. In vitro activity of penicillins against Staphylococcus albus. Proc. Soc. Exp. Biol. Med. 113:1023–1031.
    457.
    Katayama Y, Ito T, and Hiramatsu K. 2000. A new class of genetic element, staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 44:1549–1555.
    458.
    Matsuhashi M, Song MD, Ishino F, Wachi M, Doi M, Inoue M, Ubukata K, Yamashita N, and Konno M. 1986. Molecular cloning of the gene of a penicillin-binding protein supposed to cause high resistance to beta-lactam antibiotics in Staphylococcus aureus. J. Bacteriol. 167:975–980.
    459.
    Ubukata K, Nonoguchi R, Matsuhashi M, and Konno M. 1989. Expression and inducibility in Staphylococcus aureus of the mecA gene, which encodes a methicillin-resistant S. aureus-specific penicillin-binding protein. J. Bacteriol. 171:2882–2885.
    460.
    Ubukata K, Nonoguchi R, Song MD, Matsuhashi M, and Konno M. 1990. Homology of mecA gene in methicillin-resistant Staphylococcus haemolyticus and Staphylococcus simulans to that of Staphylococcus aureus. Antimicrob. Agents Chemother. 34:170–172.
    461.
    Ito T, Hiramatsu K, Tomasz A, de Lencastre H, Perreten V, Holden MT, Coleman DC, Goering R, Giffard PM, Skov RL, Zhang K, Westh H, O'Brien F, Tenover FC, Oliveira DC, Boyle-Vavra S, Laurent F, Kearns AM, Kreiswirth B, Ko KS, Grundmann H, Sollid JE, John JF Jr, Daum R, Soderquist B, and Buist G. 2012. Guidelines for reporting novel mecA gene homologues. Antimicrob. Agents Chemother. 56:4997–4999.
    462.
    Monecke S, Müller E, Schwarz S, Hotzel H, and Ehricht R. 2012. Rapid microarray-based identification of different mecA alleles in staphylococci. Antimicrob. Agents Chemother. 56:5547–5554.
    463.
    Wu S, de Lencastre H, and Tomasz A. 1998. Genetic organization of the mecA region in methicillin-susceptible and methicillin-resistant strains of Staphylococcus sciuri. J. Bacteriol. 180:236–242.
    464.
    Schnellmann C, Gerber V, Rossano A, Jaquier V, Panchaud Y, Doherr MG, Thomann A, Straub R, and Perreten V. 2006. Presence of new mecA and mph(C) variants conferring antibiotic resistance in Staphylococcus spp. isolated from the skin of horses before and after clinic admission. J. Clin. Microbiol. 44:4444–4454.
    465.
    Tsubakishita S, Kuwahara-Arai K, Sasaki T, and Hiramatsu K. 2010. Origin and molecular evolution of the determinant of methicillin resistance in staphylococci. Antimicrob. Agents Chemother. 54:4352–4359.
    466.
    Wu S, Piscitelli C, de Lencastre H, and Tomasz A. 1996. Tracking the evolutionary origin of the methicillin resistance gene: cloning and sequencing of a homologue of mecA from a methicillin susceptible strain of Staphylococcus sciuri. Microb. Drug Resist. 2:435–441.
    467.
    Couto I, de Lencastre H, Severina E, Kloos W, Webster JA, Hubner RJ, Sanches IS, and Tomasz A. 1996. Ubiquitous presence of a mecA homologue in natural isolates of Staphylococcus sciuri. Microb. Drug Resist. 2:377–391.
    468.
    Harrison EM, Paterson GK, Holden MT, Ba X, Rolo J, Morgan FJ, Pichon B, Kearns A, Zadoks RN, Peacock SJ, Parkhill J, and Holmes MA. 2014. A novel hybrid SCCmec-mecC region in Staphylococcus sciuri. J. Antimicrob. Chemother. 69:911–918.
    469.
    Tsubakishita S, Kuwahara-Arai K, Baba T, and Hiramatsu K. 2010. Staphylococcal cassette chromosome mec-like element in Macrococcus caseolyticus. Antimicrob. Agents Chemother. 54:1469–1475.
    470.
    García-Álvarez L, Holden MT, Lindsay H, Webb CR, Brown DF, Curran MD, Walpole E, Brooks K, Pickard DJ, Teale C, Parkhill J, Bentley SD, Edwards GF, Girvan EK, Kearns AM, Pichon B, Hill RL, Larsen AR, Skov RL, Peacock SJ, Maskell DJ, and Holmes MA. 2011. Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study. Lancet Infect. Dis. 11:595–603.
    471.
    Kriegeskorte A, Ballhausen B, Idelevich EA, Köck R, Friedrich AW, Karch H, Peters G, and Becker K. 2012. Human MRSA isolates with novel genetic homolog, Germany. Emerg. Infect. Dis. 18:1016–1018.
    472.
    Shore AC, Deasy EC, Slickers P, Brennan G, O'Connell B, Monecke S, Ehricht R, and Coleman DC. 2011. Detection of staphylococcal cassette chromosome mec type XI encoding highly divergent mecA, mecI, mecR1, blaZ and ccr genes in human clinical clonal complex 130 methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 55:3765–3773.
    473.
    Loncaric I, Kübber-Heiss A, Posautz A, Stalder GL, Hoffmann D, Rosengarten R, and Walzer C. 2013. Characterization of methicillin-resistant Staphylococcus spp. carrying the mecC gene, isolated from wildlife. J. Antimicrob. Chemother. 68:2222–2225.
    474.
    Harrison EM, Paterson GK, Holden MT, Morgan FJ, Larsen AR, Petersen A, Leroy S, De Vliegher S, Perreten V, Fox LK, Lam TJ, Sampimon OC, Zadoks RN, Peacock SJ, Parkhill J, and Holmes MA. 2013. A Staphylococcus xylosus isolate with a new mecC allotype. Antimicrob. Agents Chemother. 57:1524–1528.
    475.
    Malyszko I, Schwarz S, and Hauschild T. 2014. Detection of a new mecC allotype, mecC2, in methicillin-resistant Staphylococcus saprophyticus. J. Antimicrob. Chemother. 69:2003–2005.
    476.
    Hiramatsu K, Katayama Y, Yuzawa H, and Ito T. 2002. Molecular genetics of methicillin-resistant Staphylococcus aureus. Int. J. Med. Microbiol. 292:67–74.
    477.
    Hiramatsu K, Asada K, Suzuki E, Okonogi K, and Yokota T. 1992. Molecular cloning and nucleotide sequence determination of the regulator region of mecA gene in methicillin-resistant Staphylococcus aureus (MRSA). FEBS Lett. 298:133–136.
    478.
    Tesch W, Ryffel C, Strässle A, Kayser FH, and Berger-Bächi B. 1990. Evidence of a novel staphylococcal mec-encoded element (mecR) controlling expression of penicillin-binding protein 2′. Antimicrob. Agents Chemother. 34:1703–1706.
    479.
    International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements (IWG-SCC). 2009. Classification of staphylococcal cassette chromosome mec (SCCmec): guidelines for reporting novel SCCmec elements. Antimicrob. Agents Chemother. 53:4961–4967.
    480.
    Shore AC and Coleman DC. 2013. Staphylococcal cassette chromosome mec: recent advances and new insights. Int. J. Med. Microbiol. 303:350–359.
    481.
    Katayama Y, Takeuchi F, Ito T, Ma XX, Ui-Mizutani Y, Kobayashi I, and Hiramatsu K. 2003. Identification in methicillin-susceptible Staphylococcus hominis of an active primordial mobile genetic element for the staphylococcal cassette chromosome mec of methicillin-resistant Staphylococcus aureus. J. Bacteriol. 185:2711–2722.
    482.
    Bouchami O, Ben Hassen A, de Lencastre H, and Miragaia M. 2011. Molecular epidemiology of methicillin-resistant Staphylococcus hominis (MRSHo): low clonality and reservoirs of SCCmec structural elements. PLoS One 6:e21940.
    483.
    Bouchami O, Ben Hassen A, de Lencastre H, and Miragaia M. 2012. High prevalence of mec complex C and ccrC is independent of SCCmec type V in Staphylococcus haemolyticus. Eur. J. Clin. Microbiol. Infect. Dis. 31:605–614.
    484.
    Shore AC, Rossney AS, Brennan OM, Kinnevey PM, Humphreys H, Sullivan DJ, Goering RV, Ehricht R, Monecke S, and Coleman DC. 2011. Characterization of a novel arginine catabolic mobile element (ACME) and staphylococcal chromosomal cassette mec composite island with significant homology to Staphylococcus epidermidis ACME type II in methicillin-resistant Staphylococcus aureus genotype ST22-MRSA-IV. Antimicrob. Agents Chemother. 55:1896–1905.
    485.
    Miragaia M, de Lencastre H, Perdreau-Remington F, Chambers HF, Higashi J, Sullam PM, Lin J, Wong KI, King KA, Otto M, Sensabaugh GF, and Diep BA. 2009. Genetic diversity of arginine catabolic mobile element in Staphylococcus epidermidis. PLoS One 4:e7722.
    486.
    Barbier F, Lebeaux D, Hernandez D, Delannoy AS, Caro V, Francois P, Schrenzel J, Ruppe E, Gaillard K, Wolff M, Brisse S, Andremont A, and Ruimy R. 2011. High prevalence of the arginine catabolic mobile element in carriage isolates of methicillin-resistant Staphylococcus epidermidis. J. Antimicrob. Chemother. 66:29–36.
    487.
    Kinnevey PM, Shore AC, Brennan GI, Sullivan DJ, Ehricht R, Monecke S, Slickers P, and Coleman DC. 2013. Emergence of sequence type 779 methicillin-resistant Staphylococcus aureus harboring a novel pseudo staphylococcal cassette chromosome mec (SCCmec)-SCC-SCCCRISPR composite element in Irish hospitals. Antimicrob. Agents Chemother. 57:524–531.
    488.
    Mongkolrattanothai K, Boyle S, Murphy TV, and Daum RS. 2004. Novel non-mecA-containing staphylococcal chromosomal cassette composite island containing pbp4 and tagF genes in a commensal staphylococcal species: a possible reservoir for antibiotic resistance islands in Staphylococcus aureus. Antimicrob. Agents Chemother. 48:1823–1836.
    489.
    Ito T, Katayama Y, Asada K, Mori N, Tsutsumimoto K, Tiensasitorn C, and Hiramatsu K. 2001. Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 45:1323–1336.
    490.
    Shore AC, Brennan OM, Deasy EC, Rossney AS, Kinnevey PM, Ehricht R, Monecke S, and Coleman DC. 2012. DNA microarray profiling of a diverse collection of nosocomial methicillin-resistant Staphylococcus aureus isolates assigns the majority to the correct sequence type and staphylococcal cassette chromosome mec (SCCmec) type and results in the subsequent identification and characterization of novel SCCmec-SCCM1 composite islands. Antimicrob. Agents Chemother. 56:5340–5355.
    491.
    Monecke S, Engelmann I, Archambault M, Coleman DC, Coombs GW, Cortez de Jäckel S, Pelletier-Jacques G, Schwarz S, Shore AC, Slickers P, and Ehricht R. 2012. Distribution of SCCmec-associated phenol-soluble modulin in staphylococci. Mol. Cell. Probes 26:99–103.
    492.
    Hamilton-Miller JM and Iliffe A. 1985. Antimicrobial resistance in coagulase-negative staphylococci. J. Med. Microbiol. 19:217–226.
    493.
    Guggenheim M, Zbinden R, Handschin AE, Gohritz A, Altintas MA, and Giovanoli P. 2009. Changes in bacterial isolates from burn wounds and their antibiograms: a 20-year study (1986-2005). Burns 35:553–560.
    494.
    Jones ME, Karlowsky JA, Draghi DC, Thornsberry C, Sahm DF, and Nathwani D. 2003. Epidemiology and antibiotic susceptibility of bacteria causing skin and soft tissue infections in the U.S.A. and Europe: a guide to appropriate antimicrobial therapy. Int. J. Antimicrob. Agents 22:406–419.
    495.
    Sader HS and Jones RN. 2012. Antimicrobial activity of daptomycin in comparison to glycopeptides and other antimicrobials when tested against numerous species of coagulase-negative Staphylococcus. Diagn. Microbiol. Infect. Dis. 73:212–214.
    496.
    Zhanel GG, Adam HJ, Baxter MR, Fuller J, Nichol KA, Denisuik AJ, Lagacé-Wiens P, Walkty A, Karlowsky JA, Schweizer F, and Hoban DJ. 2013. Antimicrobial susceptibility of 22746 pathogens from Canadian hospitals: results of the CANWARD 2007–11 study. J. Antimicrob. Chemother. 68(Suppl 1):i7–i22.
    497.
    Mendes RE, Sader HS, and Jones RN. 2010. Activity of telavancin and comparator antimicrobial agents tested against Staphylococcus spp. isolated from hospitalised patients in Europe (2007-2008). Int. J. Antimicrob. Agents 36:374–379.
    498.
    Higashide M, Kuroda M, Omura CT, Kumano M, Ohkawa S, Ichimura S, and Ohta T. 2008. Methicillin-resistant Staphylococcus saprophyticus isolates carrying staphylococcal cassette chromosome mec have emerged in urogenital tract infections. Antimicrob. Agents Chemother. 52:2061–2068.
    499.
    Hellmark B, Unemo M, Nilsdotter-Augustinsson Å, and Söderquist B. 2009. Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections with special focus on rifampicin and variability of the rpoB gene. Clin. Microbiol. Infect. 15:238–244.
    500.
    von Eiff C, Friedrich AW, Becker K, and Peters G. 2005. Comparative in vitro activity of ceftobiprole against staphylococci displaying normal and small-colony variant phenotypes. Antimicrob. Agents Chemother. 49:4372–4374.
    501.
    Karlowsky JA, Adam HJ, Decorby MR, Lagace-Wiens PR, Hoban DJ, and Zhanel GG. 2011. In vitro activity of ceftaroline against gram-positive and gram-negative pathogens isolated from patients in Canadian hospitals in 2009. Antimicrob. Agents Chemother. 55:2837–2846.
    502.
    Walkty A, Adam HJ, Laverdière M, Karlowsky JA, Hoban DJ, and Zhanel GG. 2011. In vitro activity of ceftobiprole against frequently encountered aerobic and facultative Gram-positive and Gram-negative bacterial pathogens: results of the CANWARD 2007–2009 study. Diagn. Microbiol. Infect. Dis. 69:348–355.
    503.
    Sader HS, Flamm RK, and Jones RN. 2013. Antimicrobial activity of ceftaroline tested against staphylococci with reduced susceptibility to linezolid, daptomycin or vancomycin from U.S.A. hospitals (2008-2011). Antimicrob. Agents Chemother. 57:3178–3181.
    504.
    Sieradzki K, Villari P, and Tomasz A. 1998. Decreased susceptibilities to teicoplanin and vancomycin among coagulase-negative methicillin-resistant clinical isolates of staphylococci. Antimicrob. Agents Chemother. 42:100–107.
    505.
    Hiramatsu K, Aritaka N, Hanaki H, Kawasaki S, Hosoda Y, Hori S, Fukuchi Y, and Kobayashi I. 1997. Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet 350:1670–1673.
    506.
    Cui L, Ma X, Sato K, Okuma K, Tenover FC, Mamizuka EM, Gemmell CG, Kim MN, Ploy MC, El-Solh N, Ferraz V, and Hiramatsu K. 2003. Cell wall thickening is a common feature of vancomycin resistance in Staphylococcus aureus. J. Clin. Microbiol. 41:5–14.
    507.
    Boyle-Vavra S, Labischinski H, Ebert CC, Ehlert K, and Daum RS. 2001. A spectrum of changes occurs in peptidoglycan composition of glycopeptide-intermediate clinical Staphylococcus aureus isolates. Antimicrob. Agents Chemother. 45:280–287.
    508.
    Howden BP, Davies JK, Johnson PD, Stinear TP, and Grayson ML. 2010. Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clin. Microbiol. Rev. 23:99–139.
    509.
    Howden BP, Smith DJ, Mansell A, Johnson PD, Ward PB, Stinear TP, and Davies JK. 2008. Different bacterial gene expression patterns and attenuated host immune responses are associated with the evolution of low-level vancomycin resistance during persistent methicillin-resistant Staphylococcus aureus bacteraemia. BMC Microbiol. 8:39.
    510.
    Giovanetti E, Biavasco F, Pugnaloni A, Lupidi R, Biagini G, and Varaldo PE. 1996. An electron microscopic study of clinical and laboratory-derived strains of teicoplanin-resistant Staphylococcus haemolyticus. Microb. Drug Resist. 2:239–243.
    511.
    Sanyal D and Greenwood D. 1993. An electron microscope study of glycopeptide antibiotic-resistant strains of Staphylococcus epidermidis. J. Med. Microbiol. 39:204–210.
    512.
    Biavasco F, Vignaroli C, and Varaldo PE. 2000. Glycopeptide resistance in coagulase-negative staphylococci. Eur. J. Clin. Microbiol. Infect. Dis. 19:403–417.
    513.
    Centers for Disease Control and Prevention. 2002. Staphylococcus aureus resistant to vancomycin—United States, 2002. MMWR Morb. Mortal. Wkly. Rep. 51:565–567.
    514.
    Ishihara S, Bitner JJ, Farley GH, and Gillock ET. 2013. Vancomycin-resistant gram-positive cocci isolated from the saliva of wild songbirds. Curr. Microbiol. 66:337–343.
    515.
    Okee MS, Joloba ML, Okello M, Najjuka FC, Katabazi FA, Bwanga F, Nanteza A, and Kateete DP. 2012. Prevalence of virulence determinants in Staphylococcus epidermidis from ICU patients in Kampala, Uganda. J. Infect. Dev. Ctries. 6:242–250.
    516.
    Steinkraus G, White R, and Friedrich L. 2007. Vancomycin MIC creep in non-vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-susceptible clinical methicillin-resistant S. aureus (MRSA) blood isolates from 2001–05. J. Antimicrob. Chemother. 60:788–794.
    517.
    Wang G, Hindler JF, Ward KW, and Bruckner DA. 2006. Increased vancomycin MICs for Staphylococcus aureus clinical isolates from a university hospital during a 5-year period. J. Clin. Microbiol. 44:3883–3886.
    518.
    Holmes RL and Jorgensen JH. 2008. Inhibitory activities of 11 antimicrobial agents and bactericidal activities of vancomycin and daptomycin against invasive methicillin-resistant Staphylococcus aureus isolates obtained from 1999 through 2006. Antimicrob. Agents Chemother. 52:757–760.
    519.
    Musta AC, Riederer K, Shemes S, Chase P, Jose J, Johnson LB, and Khatib R. 2009. Vancomycin MIC plus heteroresistance and outcome of methicillin-resistant Staphylococcus aureus bacteremia: trends over 11 years. J. Clin. Microbiol. 47:1640–1644.
    520.
    Ahlstrand E, Svensson K, Persson L, Tidefelt U, and Söderquist B. 2011. Glycopeptide resistance in coagulase-negative staphylococci isolated in blood cultures from patients with hematological malignancies during three decades. Eur. J. Clin. Microbiol. Infect. Dis. 30:1349–1354.
    521.
    Schwalbe RS, Stapleton JT, and Gilligan PH. 1987. Emergence of vancomycin resistance in coagulase-negative staphylococci. N. Engl. J. Med. 316:927–931.
    522.
    Tuazon CU and Miller H. 1983. Clinical and microbiologic aspects of serious infections caused by Staphylococcus epidermidis. Scand. J. Infect. Dis. 15:347–360.
    523.
    Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, and Tenover FC. 1997. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J. Antimicrob. Chemother. 40:135–136.
    524.
    Tacconelli E, Tumbarello M, Donati KG, Bettio M, Spanu T, Leone F, Sechi LA, Zanetti S, Fadda G, and Cauda R. 2001. Glycopeptide resistance among coagulase-negative staphylococci that cause bacteremia: epidemiological and clinical findings from a case-control study. Clin. Infect. Dis. 33:1628–1635.
    525.
    Kratzer C, Rabitsch W, Hirschl AM, Graninger W, and Presterl E. 2007. In vitro activity of daptomycin and tigecycline against coagulase-negative staphylococcus blood isolates from bone marrow transplant recipients. Eur. J. Haematol. 79:405–409.
    526.
    Karlowsky JA, Adam HJ, Poutanen SM, Hoban DJ, and Zhanel GG. 2011. In vitro activity of dalbavancin and telavancin against staphylococci and streptococci isolated from patients in Canadian hospitals: results of the CANWARD 2007–2009 study. Diagn. Microbiol. Infect. Dis. 69:342–347.
    527.
    Arias CA, Reyes J, Zúñiga M, Cortés L, Cruz C, Rico CL, and Panesso D. 2003. Multicentre surveillance of antimicrobial resistance in enterococci and staphylococci from Colombian hospitals, 2001–2002. J. Antimicrob. Chemother. 51:59–68.
    528.
    Natoli S, Fontana C, Favaro M, Bergamini A, Testore GP, Minelli S, Bossa MC, Casapulla M, Broglio G, Beltrame A, Cudillo L, Cerretti R, and Leonardis F. 2009. Characterization of coagulase-negative staphylococcal isolates from blood with reduced susceptibility to glycopeptides and therapeutic options. BMC Infect. Dis. 9:83.
    529.
    Peters G and Pulverer G. 1983. Antibacterial activity of teichomycin, a new glycopeptide antibiotic, in comparison to vancomycin. J. Antimicrob. Chemother. 11:94–95.
    530.
    Fainstein V, LeBlanc B, and Bodey GP. 1983. Comparative in vitro study of teichomycin A2. Antimicrob. Agents Chemother. 23:497–499.
    531.
    Del Bene VE, John JF Jr, Twitty JA, and Lewis JW. 1986. Anti-staphylococcal activity of teicoplanin, vancomycin, and other antimicrobial agents: the significance of methicillin resistance. J. Infect. Dis. 154:349–352.
    532.
    Wilson AP, O'Hare MD, Felmingham D, and Gruneberg RN. 1986. Teicoplanin-resistant coagulase-negative Staphylococcus. Lancet 328:973.
    533.
    Grant AC, Lacey RW, Brownjohn AM, and Turney JH. 1986. Teicoplanin-resistant coagulase-negative Staphylococcus. Lancet 328:1166–1167.
    534.
    Flamm RK, Mendes RE, Ross JE, Sader HS, and Jones RN. 2013. Linezolid surveillance results for the United States: LEADER surveillance program 2011. Antimicrob. Agents Chemother. 57:1077–1081.
    535.
    Guzek A, Korzeniewski K, Nitsch-Osuch A, Rybicki Z, and Prokop E. 2013. In vitro susceptibility of staphylococci and enterococci to vancomycin and teicoplanin. Adv. Exp. Med. Biol. 788:125–132.
    536.
    Trueba F, Garrabe E, Hadef R, Fabre R, Cavallo JD, Tsvetkova K, and Chesneau O. 2006. High prevalence of teicoplanin resistance among Staphylococcus epidermidis strains in a 5-year retrospective study. J. Clin. Microbiol. 44:1922–1923.
    537.
    Hope R, Livermore DM, Brick G, Lillie M, and Reynolds R. 2008. Non-susceptibility trends among staphylococci from bacteraemias in the UK and Ireland, 2001–06. J. Antimicrob. Chemother. 62(Suppl 2):ii65–ii74.
    538.
    Friedman L, Alder JD, and Silverman JA. 2006. Genetic changes that correlate with reduced susceptibility to daptomycin in Staphylococcus aureus. Antimicrob. Agents Chemother. 50:2137–2145.
    539.
    Bayer AS, Schneider T, and Sahl HG. 2013. Mechanisms of daptomycin resistance in Staphylococcus aureus: role of the cell membrane and cell wall. Ann. N. Y. Acad. Sci. 1277:139–158.
    540.
    Yang SJ, Kreiswirth BN, Sakoulas G, Yeaman MR, Xiong YQ, Sawa A, and Bayer AS. 2009. Enhanced expression of dltABCD is associated with the development of daptomycin nonsusceptibility in a clinical endocarditis isolate of Staphylococcus aureus. J. Infect. Dis. 200:1916–1920.
    541.
    Bertsche U, Yang SJ, Kuehner D, Wanner S, Mishra NN, Roth T, Nega M, Schneider A, Mayer C, Grau T, Bayer AS, and Weidenmaier C. 2013. Increased cell wall teichoic acid production and d-alanylation are common phenotypes among daptomycin-resistant methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. PLoS One 8:e67398.
    542.
    Zhanel GG, Calic D, Schweizer F, Zelenitsky S, Adam H, Lagace-Wiens PR, Rubinstein E, Gin AS, Hoban DJ, and Karlowsky JA. 2010. New lipoglycopeptides: a comparative review of dalbavancin, oritavancin and telavancin. Drugs 70:859–886.
    543.
    Putnam SD, Sader HS, Moet GJ, Mendes RE, and Jones RN. 2010. Worldwide summary of telavancin spectrum and potency against Gram-positive pathogens: 2007 to 2008 surveillance results. Diagn. Microbiol. Infect. Dis. 67:359–368.
    544.
    Hope R, Chaudhry A, Adkin R, and Livermore DM. 2013. In vitro activity of telavancin and comparators against selected groups of Gram-positive cocci. Int. J. Antimicrob. Agents 41:213–217.
    545.
    Kloss P, Xiong L, Shinabarger DL, and Mankin AS. 1999. Resistance mutations in 23S rRNA identify the site of action of the protein synthesis inhibitor linezolid in the ribosomal peptidyl transferase center. J. Mol. Biol. 294:93–101.
    546.
    Pillai SK, Sakoulas G, Wennersten C, Eliopoulos GM, Moellering RC Jr, Ferraro MJ, and Gold HS. 2002. Linezolid resistance in Staphylococcus aureus: characterization and stability of resistant phenotype. J. Infect. Dis. 186:1603–1607.
    547.
    Locke JB, Hilgers M, and Shaw KJ. 2009. Novel ribosomal mutations in Staphylococcus aureus strains identified through selection with the oxazolidinones linezolid and torezolid (TR-700). Antimicrob. Agents Chemother. 53:5265–5274.
    548.
    Toh SM, Xiong L, Arias CA, Villegas MV, Lolans K, Quinn J, and Mankin AS. 2007. Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid. Mol. Microbiol. 64:1506–1514.
    549.
    Quiles-Melero I, Gómez-Gil R, Romero-Gómez MP, Sánchez-Díaz AM, de Pablos M, García-Rodriguez J, Gutiérrez A, and Mingorance J. 2013. Mechanisms of linezolid resistance among staphylococci in a tertiary hospital. J. Clin. Microbiol. 51:998–1001.
    550.
    Pournaras S, Ntokou E, Zarkotou O, Ranellou K, Themeli-Digalaki K, Stathopoulos C, and Tsakris A. 2013. Linezolid dependence in Staphylococcus epidermidis bloodstream isolates. Emerg. Infect. Dis. 19:129–132.
    551.
    Mazzariol A, Kocsis E, Bragagnolo L, Pellizzer G, Rassu M, and Cornaglia G. 2012. Co-infection by two linezolid-resistant coagulase-negative staphylococci with two different resistance determinants. Scand. J. Infect. Dis. 44:978–981.
    552.
    Long KS, Poehlsgaard J, Kehrenberg C, Schwarz S, and Vester B. 2006. The Cfr rRNA methyltransferase confers resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antibiotics. Antimicrob. Agents Chemother. 50:2500–2505.
    553.
    Bonilla H, Huband MD, Seidel J, Schmidt H, Lescoe M, McCurdy SP, Lemmon MM, Brennan LA, Tait-Kamradt A, Puzniak L, and Quinn JP. 2010. Multicity outbreak of linezolid-resistant Staphylococcus epidermidis associated with clonal spread of a cfr-containing strain. Clin. Infect. Dis. 51:796–800.
    554.
    Baos E, Candel FJ, Merino P, Pena I, and Picazo JJ. 2013. Characterization and monitoring of linezolid-resistant clinical isolates of Staphylococcus epidermidis in an intensive care unit 4 years after an outbreak of infection by cfr-mediated linezolid-resistant Staphylococcus aureus. Diagn. Microbiol. Infect. Dis. 76:325–329.
    555.
    Shen J, Wang Y, and Schwarz S. 2013. Presence and dissemination of the multiresistance gene cfr in Gram-positive and Gram-negative bacteria. J. Antimicrob. Chemother. 68:1697–1706.
    556.
    Rybak MJ, Cappelletty DM, Moldovan T, Aeschlimann JR, and Kaatz GW. 1998. Comparative in vitro activities and postantibiotic effects of the oxazolidinone compounds eperezolid (PNU-100592) and linezolid (PNU-100766) versus vancomycin against Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, and Enterococcus faecium. Antimicrob. Agents Chemother. 42:721–724.
    557.
    Beibei L, Yun C, Mengli C, Nan B, Xuhong Y, and Rui W. 2010. Linezolid versus vancomycin for the treatment of gram-positive bacterial infections: meta-analysis of randomised controlled trials. Int. J. Antimicrob. Agents 35:3–12.
    558.
    Walkey AJ, O'Donnell MR, and Wiener RS. 2011. Linezolid vs glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a meta-analysis of randomized controlled trials. Chest 139:1148–1155.
    559.
    Flamm RK, Mendes RE, Ross JE, Sader HS, and Jones RN. 2013. An international activity and spectrum analysis of linezolid: ZAAPS Program results for 2011. Diagn. Microbiol. Infect. Dis. 76:206–213.
    560.
    Gu B, Kelesidis T, Tsiodras S, Hindler J, and Humphries RM. 2013. The emerging problem of linezolid-resistant Staphylococcus. J. Antimicrob. Chemother. 68:4–11.
    561.
    Biedenbach DJ, Farrell DJ, Mendes RE, Ross JE, and Jones RN. 2010. Stability of linezolid activity in an era of mobile oxazolidinone resistance determinants: results from the 2009 Zyvox® Annual Appraisal of Potency and Spectrum program. Diagn. Microbiol. Infect. Dis. 68:459–467.
    562.
    Kresken M, Leitner E, Seifert H, Peters G, and von Eiff C. 2009. Susceptibility of clinical isolates of frequently encountered bacterial species to tigecycline one year after the introduction of this new class of antibiotics: results of the second multicentre surveillance trial in Germany (G-TEST II, 2007). Eur. J. Clin. Microbiol. Infect. Dis. 28:1007–1011.
    563.
    Mihaila L, Defrance G, Levesque E, Ichai P, Garnier F, Derouin V, Decousser JW, Doucet-Populaire F, and Bourgeois-Nicolaos N. 2012. A dual outbreak of bloodstream infections with linezolid-resistant Staphylococcus epidermidis and Staphylococcus pettenkoferi in a liver intensive care unit. Int. J. Antimicrob. Agents 40:472–474.
    564.
    Bongiorno D, Campanile F, Mongelli G, Baldi MT, Provenzani R, Reali S, Lo RC, Santagati M, and Stefani S. 2010. DNA methylase modifications and other linezolid resistance mutations in coagulase-negative staphylococci in Italy. J. Antimicrob. Chemother. 65:2336–2340.
    565.
    Schwarz S, Werckenthin C, and Kehrenberg C. 2000. Identification of a plasmid-borne chloramphenicol-florfenicol resistance gene in Staphylococcus sciuri. Antimicrob. Agents Chemother. 44:2530–2533.
    566.
    Mendes RE, Deshpande LM, Castanheira M, Dipersio J, Saubolle MA, and Jones RN. 2008. First report of cfr-mediated resistance to linezolid in human staphylococcal clinical isolates recovered in the United States. Antimicrob. Agents Chemother. 52:2244–2246.
    567.
    Cui L, Wang Y, Li Y, He T, Schwarz S, Ding Y, Shen J, and Lv Y. 2013. Cfr-mediated linezolid-resistance among methicillin-resistant coagulase-negative staphylococci from infections of humans. PLoS One 8:e57096.
    568.
    Yang XJ, Chen Y, Yang Q, Qu TT, Liu LL, Wang HP, and Yu YS. 2013. Emergence of cfr-harbouring coagulase-negative staphylococci among patients receiving linezolid therapy in two hospitals in China. J. Med. Microbiol. 62:845–850.
    569.
    Wang Y, He T, Schwarz S, Zhao Q, Shen Z, Wu C, and Shen J. 2013. Multidrug resistance gene cfr in methicillin-resistant coagulase-negative staphylococci from chickens, ducks, and pigs in China. Int. J. Med. Microbiol. 303:84–87.
    570.
    de Almeida LM, Lincopan N, de Araújo MR, and Mamizuka EM. 2012. Clonal dissemination of linezolid-resistant Staphylococcus haemolyticus exhibiting the G2576T mutation in the 23S rRNA gene in a tertiary care hospital in Brazil. Antimicrob. Agents Chemother. 56:2792–2793.
    571.
    Connell SR, Tracz DM, Nierhaus KH, and Taylor DE. 2003. Ribosomal protection proteins and their mechanism of tetracycline resistance. Antimicrob. Agents Chemother. 47:3675–3681.
    572.
    Butaye P, Cloeckaert A, and Schwarz S. 2003. Mobile genes coding for efflux-mediated antimicrobial resistance in Gram-positive and Gram-negative bacteria. Int. J. Antimicrob. Agents 22:205–210.
    573.
    Barros EM, Ceotto H, Bastos MC, dos Santos KR, and Giambiagi-deMarval M. 2012. Staphylococcus haemolyticus as an important hospital pathogen and carrier of methicillin resistance genes. J. Clin. Microbiol. 50:166–168.
    574.
    Coenen S, Adriaenssens N, Versporten A, Muller A, Minalu G, Faes C, Vankerckhoven V, Aerts M, Hens N, Molenberghs G, and Goossens H. 2011. European Surveillance of Antimicrobial Consumption (ESAC): outpatient use of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in Europe (1997–2009). J. Antimicrob. Chemother. 66(Suppl 6):vi57–vi70.
    575.
    Chopra I. 2002. New developments in tetracycline antibiotics: glycylcyclines and tetracycline efflux pump inhibitors. Drug Resist. Updat. 5:119–125.
    576.
    McAleese F, Petersen P, Ruzin A, Dunman PM, Murphy E, Projan SJ, and Bradford PA. 2005. A novel MATE family efflux pump contributes to the reduced susceptibility of laboratory-derived Staphylococcus aureus mutants to tigecycline. Antimicrob. Agents Chemother. 49:1865–1871.
    577.
    Sader HS, Flamm RK, and Jones RN. 2013. Antimicrobial activity of daptomycin tested against Gram-positive pathogens collected in Europe, Latin America, and selected countries in the Asia-Pacific Region (2011). Diagn. Microbiol. Infect. Dis. 75:417–422.
    578.
    Forrest GN and Tamura K. 2010. Rifampin combination therapy for nonmycobacterial infections. Clin. Microbiol. Rev. 23:14–34.
    579.
    Johanson U and Hughes D. 1994. Fusidic acid-resistant mutants define three regions in elongation factor G of Salmonella typhimurium. Gene 143:55–59.
    580.
    O'Brien FG, Price C, Grubb WB, and Gustafson JE. 2002. Genetic characterization of the fusidic acid and cadmium resistance determinants of Staphylococcus aureus plasmid pUB101. J. Antimicrob. Chemother. 50:313–321.
    581.
    Nagaev I, Björkman J, Andersson DI, and Hughes D. 2001. Biological cost and compensatory evolution in fusidic acid-resistant Staphylococcus aureus. Mol. Microbiol. 40:433–439.
    582.
    O'Neill AJ, McLaws F, Kahlmeter G, Henriksen AS, and Chopra I. 2007. Genetic basis of resistance to fusidic acid in staphylococci. Antimicrob. Agents Chemother. 51:1737–1740.
    583.
    Norström T, Lannergård J, and Hughes D. 2007. Genetic and phenotypic identification of fusidic acid-resistant mutants with the small-colony-variant phenotype in Staphylococcus aureus. Antimicrob. Agents Chemother. 51:4438–4446.
    584.
    Castanheira M, Watters AA, Bell JM, Turnidge JD, and Jones RN. 2010. Fusidic acid resistance rates and prevalence of resistance mechanisms among Staphylococcus spp. isolated in North America and Australia, 2007–2008. Antimicrob. Agents Chemother. 54:3614–3617.
    585.
    Castanheira M, Watters AA, Mendes RE, Farrell DJ, and Jones RN. 2010. Occurrence and molecular characterization of fusidic acid resistance mechanisms among Staphylococcus spp. from European countries (2008). J. Antimicrob. Chemother. 65:1353–1358.
    586.
    Mlynarczyk A, Mlynarczyk G, Bardowski J, and Osowiecki H. 1985. Chromosomal localization of resistance to fosfomycin and aminocyclitol antibiotics in hospital strains of Staphylococcus aureus. Acta Microbiol. Pol. 34:145–154.
    587.
    Llaneza J, Villar CJ, Salas JA, Suarez JE, Mendoza MC, and Hardisson C. 1985. Plasmid-mediated fosfomycin resistance is due to enzymatic modification of the antibiotic. Antimicrob. Agents Chemother. 28:163–164.
    588.
    Etienne J, Gerbaud G, Courvalin P, and Fleurette J. 1989. Plasmid-mediated resistance to fosfomycin in Staphylococcus epidermidis. FEMS Microbiol. Lett. 52:133–137.
    589.
    Falagas ME, Roussos N, Gkegkes ID, Rafailidis PI, and Karageorgopoulos DE. 2009. Fosfomycin for the treatment of infections caused by Gram-positive cocci with advanced antimicrobial drug resistance: a review of microbiological, animal and clinical studies. Expert Opin. Invest. Drugs 18:921–944.
    590.
    Falagas ME, Maraki S, Karageorgopoulos DE, Kastoris AC, Kapaskelis A, and Samonis G. 2010. Antimicrobial susceptibility of Gram-positive non-urinary isolates to fosfomycin. Int. J. Antimicrob. Agents 35:497–499.
    591.
    Campbell EA, Korzheva N, Mustaev A, Murakami K, Nair S, Goldfarb A, and Darst SA. 2001. Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell 104:901–912.
    592.
    Tupin A, Gualtieri M, Roquet-Baneres F, Morichaud Z, Brodolin K, and Leonetti JP. 2010. Resistance to rifampicin: at the crossroads between ecological, genomic and medical concerns. Int. J. Antimicrob. Agents 35:519–523.
    593.
    Kresken M, Hafner D, Schmitz FJ, and Wichelhaus TA. 2004. Prevalence of mupirocin resistance in clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis: results of the Antimicrobial Resistance Surveillance Study of the Paul-Ehrlich-Society for Chemotherapy, 2001. Int. J. Antimicrob. Agents 23:577–581.
    594.
    Bathoorn E, Hetem DJ, Alphenaar J, Kusters JG, and Bonten MJ. 2012. Emergence of high-level mupirocin resistance in coagulase-negative staphylococci associated with increased short-term mupirocin use. J. Clin. Microbiol. 50:2947–2950.
    595.
    Berg T, Firth N, Apisiridej S, Hettiaratchi A, Leelaporn A, and Skurray RA. 1998. Complete nucleotide sequence of pSK41: evolution of staphylococcal conjugative multiresistance plasmids. J. Bacteriol. 180:4350–4359.
    596.
    Walsh TR, Bolmstrom A, Qwarnstrom A, Ho P, Wootton M, Howe RA, MacGowan AP, and Diekema D. 2001. Evaluation of current methods for detection of staphylococci with reduced susceptibility to glycopeptides. J. Clin. Microbiol. 39:2439–2444.
    597.
    Nunes AP, Teixeira LM, Iorio NL, Bastos CC, de Sousa Fonseca L, Souto-Padrón T, and dos Santos KR. 2006. Heterogeneous resistance to vancomycin in Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus warneri clinical strains: characterisation of glycopeptide susceptibility profiles and cell wall thickening. Int. J. Antimicrob. Agents 27:307–315.
    598.
    Iorio NL, Azevedo MB, Frazão VH, Barcellos AG, Barros EM, Pereira EM, de Mattos CS, and dos Santos KR. 2011. Methicillin-resistant Staphylococcus epidermidis carrying biofilm formation genes: detection of clinical isolates by multiplex PCR. Int. Microbiol. 14:13–17.
    599.
    Kitao T, Ishimaru M, and Nishihara S. 2010. Detection of biofilm-producing and methicillin resistance genes in Staphylococcus epidermidis isolated from healthy humans and in blood culture tests. J. Infect. Chemother. 16:170–173.
    600.
    Uekötter A, Peters G, and Becker K. 2011. Is there any rationale for treatment of Staphylococcus aureus infections with antimicrobials that are determined to be ineffective in vitro? Clin. Microbiol. Infect. 17:1142–1147.
    601.
    Deresinski S. 2009. Vancomycin in combination with other antibiotics for the treatment of serious methicillin-resistant Staphylococcus aureus infections. Clin. Infect. Dis. 49:1072–1079.
    602.
    Guay DR. 2008. Contemporary management of uncomplicated urinary tract infections. Drugs 68:1169–1205.
    603.
    Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Bolger AF, Levison ME, Ferrieri P, Gerber MA, Tani LY, Gewitz MH, Tong DC, Steckelberg JM, Baltimore RS, Shulman ST, Burns JC, Falace DA, Newburger JW, Pallasch TJ, Takahashi M, and Taubert KA. 2005. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association. Circulation 111:e394–e434.
    604.
    Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, Saint S, Schaeffer AJ, Tambayh PA, Tenke P, and Nicolle LE. 2010. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 international clinical practice guidelines from the Infectious Diseases Society of America. Clin. Infect. Dis. 50:625–663.
    605.
    Gilbert DN, Moellering RC Jr, Eliopoulos GM, Chambers HF, and Saag MS. 2013. The Sanford guide to antimicrobial therapy. Antimicrobial Therapy, Inc, Sperryville, VA.
    606.
    Olson ME, Ceri H, Morck DW, Buret AG, and Read RR. 2002. Biofilm bacteria: formation and comparative susceptibility to antibiotics. Can. J. Vet. Res. 66:86–92.
    607.
    Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, Raad II, Rijnders BJ, Sherertz RJ, and Warren DK. 2009. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin. Infect. Dis. 49:1–45.
    608.
    Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W, Steckelberg JM, Rao N, Hanssen A, and Wilson WR. 2013. Executive summary: diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin. Infect. Dis. 56:1–10.
    609.
    O'Horo JC, Silva GLM, and Safdar N. 2011. Anti-infective locks for treatment of central line-associated bloodstream infection: a systematic review and meta-analysis. Am. J. Nephrol. 34:415–422.
    610.
    Lehmann KB and Neumann RO. 1896. Atlas und Grundriss der Bakteriologie und Lehrbuch der speciellen bakteriologischen Diagnostik. J F Lehmann, Munich, Germany.
    611.
    Evans AC. 1916. The bacteria of milk freshly drawn from normal udders. J. Infect. Dis. 18:437–476.
    612.
    Skerman VBD, McGowan V, and Sneath PHA. 1980. Approved lists of bacterial names. Int. J. Syst. Bacteriol. 30:225–420.
    613.
    Passet J. 1885. Ueber Mikroorganismen der eiterigen Zellgewebsentzündung des Menschen. Fortschr. Med. 3:33–43.
    614.
    Petinaki E, Kontos F, Miriagou V, Maniati M, Hatzi F, and Maniatis AN. 2001. Survey of methicillin-resistant coagulase-negative staphylococci in the hospitals of central Greece. Int. J. Antimicrob. Agents 18:563–566.
    615.
    Cuevas O, Cercenado E, Vindel A, Guinea J, Sanchez-Conde M, Sanchez-Somolinos M, and Bouza E. 2004. Evolution of the antimicrobial resistance of Staphylococcus spp. in Spain: five nationwide prevalence studies, 1986 to 2002. Antimicrob. Agents Chemother. 48:4240–4245.
    616.
    Sivadon V, Rottman M, Chaverot S, Quincampoix JC, Avettand V, de Mazancourt P, Bernard L, Trieu-Cuot P, Féron JM, Lortat-Jacob A, Piriou P, Judet T, and Gaillard JL. 2005. Use of genotypic identification by sodA sequencing in a prospective study to examine the distribution of coagulase-negative Staphylococcus species among strains recovered during septic orthopedic surgery and evaluate their significance. J. Clin. Microbiol. 43:2952–2954.
    617.
    Gatermann SG, Koschinski T, and Friedrich S. 2007. Distribution and expression of macrolide resistance genes in coagulase-negative staphylococci. Clin. Microbiol. Infect. 13:777–781.
    618.
    Koksal F, Yasar H, and Samasti M. 2009. Antibiotic resistance patterns of coagulase-negative staphylococcus strains isolated from blood cultures of septicemic patients in Turkey. Microbiol. Res. 164:404–410.
    619.
    Jain A, Agarwal A, Verma RK, Awasthi S, and Singh KP. 2011. Intravenous device associated blood stream staphylococcal infection in paediatric patients. Indian J. Med. Res. 134:193–199.
    620.
    Gillespie BE, Headrick SI, Boonyayatra S, and Oliver SP. 2009. Prevalence and persistence of coagulase-negative Staphylococcus species in three dairy research herds. Vet. Microbiol. 134:65–72.
    621.
    Coton E, Desmonts MH, Leroy S, Coton M, Jamet E, Christieans S, Donnio PY, Lebert I, and Talon R. 2010. Biodiversity of coagulase-negative staphylococci in French cheeses, dry fermented sausages, processing environments and clinical samples. Int. J. Food Microbiol. 137:221–229.
    622.
    Hauschild T, Slizewski P, and Masiewicz P. 2010. Species distribution of staphylococci from small wild mammals. Syst. Appl. Microbiol. 33:457–460.
    623.
    Leroy S, Giammarinaro P, Chacornac JP, Lebert I, and Talon R. 2010. Biodiversity of indigenous staphylococci of naturally fermented dry sausages and manufacturing environments of small-scale processing units. Food Microbiol. 27:294–301.
    624.
    Huber H, Ziegler D, Pflüger V, Vogel G, Zweifel C, and Stephan R. 2011. Prevalence and characteristics of methicillin-resistant coagulase-negative staphylococci from livestock, chicken carcasses, bulk tank milk, minced meat, and contact persons. BMC Vet. Res. 7:6.
    625.
    Waller KP, Aspán A, Nyman A, Persson Y, and Andersson UG. 2011. CNS species and antimicrobial resistance in clinical and subclinical bovine mastitis. Vet. Microbiol. 152:112–116.
    626.
    Baba T, Kuwahara-Arai K, Uchiyama I, Takeuchi F, Ito T, and Hiramatsu K. 2009. Complete genome sequence of Macrococcus caseolyticus strain JCSCS5402, reflecting the ancestral genome of the human-pathogenic staphylococci. J. Bacteriol. 191:1180–1190.
    627.
    Mombach Pinheiro Machado AB, Reiter KC, Paiva RM, and Barth AL. 2007. Distribution of staphylococcal cassette chromosome mec (SCCmec) types I, II, III and IV in coagulase-negative staphylococci from patients attending a tertiary hospital in southern Brazil. J. Med. Microbiol. 56:1328–1333.
    628.
    Ibrahem S, Salmenlinna S, Virolainen A, Kerttula AM, Lyytikäinen O, Jägerroos Broas HM, and Vuopio-Varkila J. 2009. Carriage of methicillin-resistant staphylococci and their SCCmec types in a long-term-care facility. J. Clin. Microbiol. 47:32–37.
    629.
    Kern A and Perreten V. 2013. Clinical and molecular features of methicillin-resistant, coagulase-negative staphylococci of pets and horses. J. Antimicrob. Chemother. 68:1256–1266.
    630.
    Al-Bakri AG, Al-Hadithi H, Kasabri V, Othman G, Kriegeskorte A, and Becker K. 2013. The epidemiology and molecular characterization of methicillin-resistant staphylococci sampled from a healthy Jordanian population. Epidemiol. Infect. 141:2384–2391.
    631.
    Zhang Y, Agidi S, and LeJeune JT. 2009. Diversity of staphylococcal cassette chromosome in coagulase-negative staphylococci from animal sources. J. Appl. Microbiol. 107:1375–1383.
    632.
    Hanssen AM, Kjeldsen G, and Sollid JU. 2004. Local variants of staphylococcal cassette chromosome mec in sporadic methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci: evidence of horizontal gene transfer? Antimicrob. Agents Chemother. 48:285–296.
    633.
    Malik S, Coombs GW, O'Brien FG, Peng H, and Barton MD. 2006. Molecular typing of methicillin-resistant staphylococci isolated from cats and dogs. J. Antimicrob. Chemother. 58:428–431.
    634.
    Vanderhaeghen W, Vandendriessche S, Crombé F, Dispas M, Denis O, Hermans K, Haesebrouck F, and Butaye P. 2012. Species and staphylococcal cassette chromosome mec (SCCmec) diversity among methicillin-resistant non-Staphylococcus aureus staphylococci isolated from pigs. Vet. Microbiol. 158:123–128.
    635.
    Garza-González E, Morfín-Otero R, Llaca-Díaz JM, and Rodriguez-Noriega E. 2010. Staphylococcal cassette chromosome mec (SCCmec) in methicillin-resistant coagulase-negative staphylococci. A review and the experience in a tertiary-care setting. Epidemiol. Infect. 138:645–654.
    636.
    Pi B, Yu M, Chen Y, Yu Y, and Li L. 2009. Distribution of the ACME-arcA gene among meticillin-resistant Staphylococcus haemolyticus and identification of a novel ccr allotype in ACME-arcA-positive isolates. J. Med. Microbiol. 58:731–736.
    637.
    Hammad AM, Watanabe W, Fujii T, and Shimamoto T. 2012. Occurrence and characteristics of methicillin-resistant and -susceptible Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci from Japanese retail ready-to-eat raw fish. Int. J. Food Microbiol. 156:286–289.
    638.
    Söderquist B and Berglund C. 2009. Methicillin-resistant Staphylococcus saprophyticus in Sweden carries various types of staphylococcal cassette chromosome mec (SCCmec). Clin. Microbiol. Infect. 15:1176–1178.

    Author Bios

    Karsten Becker [email protected]
    Institute of Medical Microbiology, University Hospital Münster, Münster, Germany
    Karsten Becker, M.D., is Professor of Medical Microbiology, Assistant Medical Director, and Group Leader at the Institute of Medical Microbiology at the Westphalian Wilhelms University Münster. He is Chairman of the Diagnostic Procedures Standing Working Group of the German Society for Hygiene and Microbiology (DGHM) and received a research award in Clinical Infectiology from the German Society for Infectiology. He is the author of several medical textbooks and encyclopedias and more than 150 scientific publications. Since the 1990s, his interests have included the epidemiology, pathogenesis, diagnosis, prevention, and therapy of staphylococcal and micrococcal infections. He has described novel species of the genera Staphylococcus and Kytococcus. In particular, he has done extensive research on the intracellular lifestyle of the staphylococcal small-colony variant (SCV) phenotype. A further focus is on the detection, identification, and characterization of MRSA strains. He is an academic editor and a member of the editorial boards of medical and bioscience journals.
    Christine Heilmann
    Institute of Medical Microbiology, University Hospital Münster, Münster, Germany
    Christine Heilmann, Ph.D., studied biology at the Universities of Münster and Tübingen, Germany, and received her diploma (microbiology, biochemistry, genetics, and pharmacology; 1991) and Ph.D. (1996) at the University of Tübingen. She undertook her Ph.D. thesis work in the laboratory of Fritz Götz, in the Department of Microbial Genetics, Tübingen, Germany, where she discovered the icaADBC operon mediating polysaccharide-dependent staphylococcal biofilm formation. After completing her Ph.D., she carried out postdoctoral studies on staphylococcal pathogenesis at the Institute of Medical Microbiology at the University of Münster, in the laboratory of Georg Peters, and in the Channing Laboratory at Harvard Medical School, Boston, MA. Since 2001, she has been a Group Leader at the Institute of Medical Microbiology in Münster. She has worked in the area of staphylococcal research for more than 20 years, and her research focuses on the molecular basis of staphylococcal biofilm formation and host-pathogen interactions.
    Georg Peters
    Institute of Medical Microbiology, University Hospital Münster, Münster, Germany
    Georg Peters, M.D., is Head of the Institute of Medical Microbiology at the Westphalian Wilhelms University Münster. Since the beginning of his career, he has carried out research on the infectious biology of staphylococci and staphylococcal diseases. In the early 1980s, he initiated the first studies on the pathomechanisms of biofilm (“slime”) formation by S. epidermidis as the virulence principle causing foreign body infections. He is a member of the Senate of the German Research Foundation (DFG). He is a member of the Scientific Advisory Board of the Robert Koch Institute. He was President of the German Society for Hygiene and Microbiology (DGHM) and of the Paul Ehrlich Society for Chemotherapy (PEG). He served as Vice Chairman and Chairman of the Gordon Research Conference on Staphylococcal Diseases.

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    Clinical Microbiology Reviews
    Volume 27Number 4October 2014
    Pages: 870 - 926

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    Karsten Becker [email protected]
    Institute of Medical Microbiology, University Hospital Münster, Münster, Germany
    Christine Heilmann
    Institute of Medical Microbiology, University Hospital Münster, Münster, Germany
    Georg Peters
    Institute of Medical Microbiology, University Hospital Münster, Münster, Germany

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    β-Lactamase Production in Key Gram-Negative Pathogen Isolates from the Arabian Peninsula

    β-Lactamase Production in Key Gram-Negative Pathogen Isolates from the Arabian Peninsula

    SUMMARY

    Infections due to Gram-negative bacilli (GNB) are a leading cause of morbidity and mortality worldwide. The extent of antibiotic resistance in GNB in countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Oman, and Bahrain, has not been previously reviewed. These countries share a high prevalence of extended-spectrum-β-lactamase (ESBL)- and carbapenemase-producing GNB, most of which are associated with nosocomial infections. Well-known and widespread β-lactamases genes (such as those for CTX-M-15, OXA-48, and NDM-1) have found their way into isolates from the GCC states. However, less common and unique enzymes have also been identified. These include PER-7, GES-11, and PME-1. Several potential risk factors unique to the GCC states may have contributed to the emergence and spread of β-lactamases, including the unnecessary use of antibiotics and the large population of migrant workers, particularly from the Indian subcontinent. It is clear that active surveillance of antimicrobial resistance in the GCC states is urgently needed to address regional interventions that can contain the antimicrobial resistance issue.

    REFERENCES

    1.
    Kliebe C, Nies BA, Meyer JF, Tolxdorff-Neutzling RM, and Wiedemann B. 1985. Evolution of plasmid-coded resistance to broad-spectrum cephalosporins. Antimicrob. Agents Chemother. 28:302–307.
    2.
    Paterson DL. 2006. Resistance in gram-negative bacteria: Enterobacteriaceae. Am. J. Infect. Control 34:S20–S28, S64–S73.
    3.
    Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, and Walsh TR. 2009. Characterization of a new metallo-beta-lactamase gene, blaNDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob. Agents Chemother. 53:5046–5054.
    4.
    Gerner-Smidt P, Tjernberg I, and Ursing J. 1991. Reliability of phenotypic tests for identification of Acinetobacter species. J. Clin. Microbiol. 29:277–282.
    5.
    Lee YT, Kuo SC, Chiang MC, Yang SP, Chen CP, Chen TL, and Fung CP. 2012. Emergence of carbapenem-resistant non-baumannii species of Acinetobacter harboring a blaOXA-51-like gene that is intrinsic to A. baumannii. Antimicrob. Agents Chemother. 56:1124–1127.
    6.
    Abd-Elalim Eltahawy AT and Khalaf RM. 1988. Comparative in vitro activity of amoxycillin/clavulanate (augmentin), ceftazidime and ceftriaxone against hospital strains of gram-negative and -positive bacteria. Chemioterapia 7:75–78.
    7.
    Ahmad S, Al-Juaid NF, Alenzi FQ, Mattar EH, and Bakheet Oel S. 2009. Prevalence, antibiotic susceptibility pattern and production of extended-spectrum beta-lactamases amongst clinical isolates of Klebsiella pneumoniae at Armed Forces Hospital in Saudi Arabia. J. Coll. Physicians Surg. Pak. 19:264–265.
    8.
    Babay HA. 2002. Detection of extended-spectrum b-lactamases in members of the family Enterobacteriaceae at a teaching hospital, Riyadh, Kingdom of Saudi Arabia. Saudi Med. J. 23:186–190.
    9.
    El-Khizzi NA and Bakheshwain SM. 2006. Prevalence of extended-spectrum beta-lactamases among Enterobacteriaceae isolated from blood culture in a tertiary care hospital. Saudi Med. J. 27:37–40.
    10.
    Khanfar HS, Bindayna KM, Senok AC, and Botta GA. 2009. Extended spectrum beta-lactamases (ESBL) in Escherichia coli and Klebsiella pneumoniae: trends in the hospital and community settings. J. Infect. Dev. Ctries. 3:295–299.
    11.
    Aljohani S, Younan M, and Balkhy H. 2012. Prevalence and antimicrobial susceptibility of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a tertiary care hospital, abstr R2544. Abstr. 22nd Eur. Congr. Clin. Microbiol. Infect. Dis., London, United Kingdom.
    12.
    Somily A, Shakoor Z, Manneh K, and Alsubaie SMT. 2012. Five-year screening and phenotypic classification of extended-spectrum beta-lactamases producing Escherichia coli and Klebsiella pneumoniae at a tertiary care university hospital in Riyadh, Saudi Arabia, abstr P1866. Abstr. 22nd Eur. Congr. Clin. Microbiol. Infect. Dis., London, United Kingdom.
    13.
    Kader AA and Kamath KA. 2009. Faecal carriage of extended-spectrum beta-lactamase-producing bacteria in the community. East Mediterr. Health J. 15:1365–1370.
    14.
    Rotimi VO, al-Sweih NA, and Feteih J. 1998. The prevalence and antibiotic susceptibility pattern of gram-negative bacterial isolates in two ICUs in Saudi Arabia and Kuwait. Diagn. Microbiol. Infect. Dis. 30:53–59.
    15.
    Bindayna K, Khanfar HS, Senok AC, and Botta GA. 2010. Predominance of CTX-M genotype among extended spectrum beta lactamase isolates in a tertiary hospital in Saudi Arabia. Saudi Med. J. 30:859–863.
    16.
    Al-Agamy MH, Shibl AM, and Tawfik AF. 2009. Prevalence and molecular characterization of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in Riyadh, Saudi Arabia. Ann. Saudi Med. 29:253–257.
    17.
    Al-Obeid S, Bremont S, Jabri L, Massoudi N, and Haddad Q. 2008. Klebsiella pneumoniae LO10 producing extended-spectrum beta-lactamase SHV-12 in Saudi Arabia. J. Chemother. 20:709–713.
    18.
    Bush K. 2008. Extended-spectrum beta-lactamases in North America, 1987-2006. Clin. Microbiol. Infect. 14(Suppl 1):134–143.
    19.
    Coque TM, Baquero F, and Canton R. 2008. Increasing prevalence of ESBL-producing Enterobacteriaceae in Europe. Euro Surveill. 13(48):pii=19051.
    20.
    Hawkey PM. 2008. Prevalence and clonality of extended-spectrum beta-lactamases in Asia. Clin. Microbiol. Infect. 14(Suppl 1):159–165.
    21.
    Tawfik AF, Alswailem AM, Shibl AM, and Al-Agamy MH. 2011. Prevalence and genetic characteristics of TEM, SHV, and CTX-M in clinical Klebsiella pneumoniae isolates from Saudi Arabia. Microb. Drug Resist. 17:383–388.
    22.
    Paterson DL and Bonomo RA. 2005. Extended-spectrum beta-lactamases: a clinical update. Clin. Microbiol. Rev. 18:657–686.
    23.
    Tawfik AF, Shibl AM, Aljohi MA, Altammami MA, and Al-Agamy MH. 2012. Distribution of Ambler class A, B and D beta-lactamases among Pseudomonas aeruginosa isolates. Burns 38:855–860.
    24.
    Al-Agamy MH, Shibl AM, Tawfik AF, Elkhizzi NA, and Livermore DM. 2012. Extended-spectrum and metallo-beta-lactamases among ceftazidime-resistant Pseudomonas aeruginosa in Riyadh, Saudi Arabia. J. Chemother. 24:97–100.
    25.
    Ribeiro A, Al-Agamy MH, Shibl AM, Tawfik AF, Courvalin P, and Jeannot K. 2012. Molecular epidemiology and mechanisms of carbapenem-resistant Acinetobacter baumannii in a Saudi Arabia hospital, abstr P1256. Abstr. 22nd Eur. Congr. Clin. Microbiol. Infect. Dis., London, United Kingdom.
    26.
    Jacoby GA. 2009. AmpC beta-lactamases. Clin. Microbiol. Rev. 22:161–182.
    27.
    Gaillot O, Clement C, Simonet M, and Philippon A. 1997. Novel transferable beta-lactam resistance with cephalosporinase characteristics in Salmonella enteritidis. J. Antimicrob. Chemother. 39:85–87.
    28.
    Verdet C, Benzerara Y, Gautier V, Adam O, Ould-Hocine Z, and Arlet G. 2006. Emergence of DHA-1-producing Klebsiella spp. in the Parisian region: genetic organization of the ampC and ampR genes originating from Morganella morganii. Antimicrob. Agents Chemother. 50:607–617.
    29.
    Gonzalez-Sanz R, Herrera-Leon S, de la Fuente M, Arroyo M, and Echeita MA. 2009. Emergence of extended-spectrum beta-lactamases and AmpC-type beta-lactamases in human Salmonella isolated in Spain from 2001 to 2005. J. Antimicrob. Chemother. 64:1181–1186.
    30.
    Ogbolu DO, Daini OA, Ogunledun A, Alli AO, and Webber MA. 2011. High levels of multidrug resistance in clinical isolates of Gram-negative pathogens from Nigeria. Int. J. Antimicrob. Agents 37:62–66.
    31.
    Singtohin S, Chanawong A, Lulitanond A, Sribenjalux P, Auncharoen A, Kaewkes W, Songsri J, and Pienthaweechai K. 2010. CMY-2, CMY-8b, and DHA-1 plasmid-mediated AmpC beta-lactamases among clinical isolates of Escherichia coli and Klebsiella pneumoniae from a university hospital, Thailand. Diagn. Microbiol. Infect. Dis. 68:271–277.
    32.
    Yamasaki K, Komatsu M, Abe N, Fukuda S, Miyamoto Y, Higuchi T, Ono T, Nishio H, Sueyoshi N, Kida K, Satoh K, Toyokawa M, Nishi I, Sakamoto M, Akagi M, Nakai I, Kofuku T, Orita T, Wada Y, Jikimoto T, Kinoshita S, Miyamoto K, Hirai I, and Yamamoto Y. 2010. Laboratory surveillance for prospective plasmid-mediated AmpC beta-lactamases in the Kinki region of Japan. J. Clin. Microbiol. 48:3267–3273.
    33.
    Kader AA and Kumar AK. 2004. Prevalence of extended spectrum beta-lactamase among multidrug resistant gram-negative isolates from a general hospital in Saudi Arabia. Saudi Med. J. 25:570–574.
    34.
    Al Johani SM, Akhter J, Balkhy H, El-Saed A, Younan M, and Memish Z. 2010. Prevalence of antimicrobial resistance among gram-negative isolates in an adult intensive care unit at a tertiary care center in Saudi Arabia. Ann. Saudi Med. 30:364–369.
    35.
    Balkhy HH, El-Saed A, Al Johani SM, Francis C, Al-Qahtani AA, Al-Ahdal MN, Altayeb HT, Arabi Y, Alothman A, and Sallah M. 2012. The epidemiology of the first described carbapenem-resistant Klebsiella pneumoniae outbreak in a tertiary care hospital in Saudi Arabia: how far do we go? Eur. J. Clin. Microbiol. Infect. Dis. 31:1901–1909.
    36.
    Balkhy H, Uz-Zaman T, Al-Drees M, Al Johani S, Al-Qahtani A, and Al-Ahdal M. 2012. Genetic analysis of the first outbreak of carbapenem resistant Klebsiella pneumoniea in Saudi Arabia, abstr R2509. Abstr. 22nd Eur. Congr. Clin. Microbiol. Infect. Dis., London, United Kingdom.
    37.
    Poirel L, Heritier C, Tolun V, and Nordmann P. 2004. Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob. Agents Chemother. 48:15–22.
    38.
    Al-Qadheeb NS, Althawadi S, Alkhalaf A, Hosaini S, and Alrajhi AA. 2010. Evolution of tigecycline resistance in Klebsiella pneumoniae in a single patient. Ann. Saudi Med. 30:404–407.
    39.
    Eltahawy AT. 1997. Gram-negative bacilli isolated from patients in intensive care unit: prevalence and antibiotic susceptibility. J. Chemother. 9:403–410.
    40.
    Babay HA. 2007. Antimicrobial resistance among clinical isolates of Pseudomonas aeruginosa from patients in a teaching hospital, Riyadh, Saudi Arabia, 2001-2005. Jpn. J. Infect. Dis. 60:123–125.
    41.
    Memish ZA, Shibl AM, Kambal AM, Ohaly YA, Ishaq A, and Livermore DM. 2012. Antimicrobial resistance among non-fermenting Gram-negative bacteria in Saudi Arabia. J. Antimicrob. Chemother. 67:1701–1705.
    42.
    Guerin F, Henegar C, Spiridon G, Launay O, Salmon-Ceron D, and Poyart C. 2005. Bacterial prostatitis due to Pseudomonas aeruginosa harbouring the blaVIM-2 metallo-β-lactamase gene from Saudi Arabia. J. Antimicrob. Chemother. 56:601–602.
    43.
    Al-Agamy MH, Shibl AM, Tawfik AF, and Radwan HH. 2009. High prevalence of metallo-beta-lactamase-producing Pseudomonas aeruginosa from Saudi Arabia. J. Chemother. 21:461–462.
    44.
    Asghar A. 2012. Frequency and antimicrobial susceptibility of Pseudomonas aeruginosa isolated from Makkah hospitals, Saudi Arabia, abstr R2482. Abstr. 22nd Eur. Congr. Clin. Microbiol. Infect. Dis., London, United Kingdom.
    45.
    Alsultan AA, Hamouda A, Evans BA, and Amyes SG. 2009. Acinetobacter baumannii: emergence of four strains with novel blaOXA-51-like genes in patients with diabetes mellitus. J. Chemother. 21:290–295.
    46.
    Alsultan A. 2012. Emergence of carbapenem-resistant Acinetobacter baumannii producing OXA-23 gene in a major Saudi Arabian hospital, abstr p2029. . 22nd Eur. Congr. Clin. Microbiol. Infect. Dis., London, United Kingdom.
    47.
    Abdalhamid B, Itbaileh A, and Hassan H. 2012. Characterisation of carbapenem-resistant Acinetobacter baumannii clinical isolates in a tertiary care hospital in Saudi Arabia, abstr R2543. Abstr. 22nd Eur. Congr. Clin. Microbiol. Infect. Dis., London, United Kingdom.
    48.
    Al-Dhaheri AS, Al-Niyadi MS, Al-Dhaheri AD, and Bastaki SM. 2009. Resistance patterns of bacterial isolates to antimicrobials from 3 hospitals in the United Arab Emirates. Saudi Med. J. 30:618–623.
    49.
    Narchi H and Al-Hamdan MA. 2010. Antibiotic resistance trends in paediatric community-acquired first urinary tract infections in the United Arab Emirates. East Mediterr. Health J. 16:45–50.
    50.
    Dash N, Mansour ALZ, Al-Kous N, Al-Shehhi F, Al-Najjar J, Senok A, and Panigrahi D. 2008. Distribution and resistance trends of community associated urinary tract pathogens in Sharjah, UAE. Microbiol. Insights 1:41–45.
    51.
    Al-Zarouni M, Senok A, Rashid F, Al-Jesmi SM, and Panigrahi D. 2008. Prevalence and antimicrobial susceptibility pattern of extended-spectrum beta-lactamase-producing Enterobacteriaceae in the United Arab Emirates. Med. Princ. Pract. 17:32–36.
    52.
    Sonnevend A, Al Dhaheri K, Mag T, Herpay M, Kolodziejek J, Nowotny N, Usmani A, Sheikh FA, and Pal T. 2006. CTX-M-15-producing multidrug-resistant enteroaggregative Escherichia coli in the United Arab Emirates. Clin. Microbiol. Infect. 12:582–585.
    53.
    Rotimi VO, Jamal W, Pal T, Sonnevend A, Dimitrov TS, and Albert MJ. 2008. Emergence of multidrug-resistant Salmonella spp. and isolates with reduced susceptibility to ciprofloxacin in Kuwait and the United Arab Emirates. Diagn. Microbiol. Infect. Dis. 60:71–77.
    54.
    Rotimi VO, Jamal W, Pal T, Sovenned A, and Albert MJ. 2008. Emergence of CTX-M-15 type extended-spectrum beta-lactamase-producing Salmonella spp. in Kuwait and the United Arab Emirates. J. Med. Microbiol. 57:881–886.
    55.
    Jamal W, Rotimi VO, Pal T, Sonnevend A, and Dimitrov TS. 2010. Comparative in vitro activity of tigecycline and other antimicrobial agents against Shigella species from Kuwait and the United Arab of Emirates. J. Infect. Public Health 3:35–42.
    56.
    Alfaresi MS, Elkoush AA, Alshehhi HM, and Abdulsalam AI. 2011. Molecular characterization and epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates in the United Arab Emirates. Med. Princ. Pract. 20:177–180.
    57.
    Tian GB, Adams-Haduch JM, Bogdanovich T, Wang HN, and Doi Y. 2011. PME-1, an extended-spectrum β-lactamase identified in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 55:2710–2713.
    58.
    Opazo A, Sonnevend A, Lopes B, Hamouda A, Ghazawi A, Pal T, and Amyes SG. 2012. Plasmid-encoded PER-7 beta-lactamase responsible for ceftazidime resistance in Acinetobacter baumannii isolated in the United Arab Emirates. J. Antimicrob. Chemother. 67:1619–1622.
    59.
    Bonnin RA, Potron A, Poirel L, Lecuyer H, Neri R, and Nordmann P. 2011. PER-7, an extended-spectrum beta-lactamase with increased activity toward broad-spectrum cephalosporins in Acinetobacter baumannii. Antimicrob. Agents Chemother. 55:2424–2427.
    60.
    Vahaboglu H, Ozturk R, Aygun G, Coskunkan F, Yaman A, Kaygusuz A, Leblebicioglu H, Balik I, Aydin K, and Otkun M. 1997. Widespread detection of PER-1-type extended-spectrum beta-lactamases among nosocomial Acinetobacter and Pseudomonas aeruginosa isolates in Turkey: a nationwide multicenter study. Antimicrob. Agents Chemother. 41:2265–2269.
    61.
    Sonnevend A, Ghazawi A, Yahfoufi N, Al-Baloushi A, Hashmey R, Mathew M, Tariq WZ, and Pal T. 2012. VIM-4 carbapenemase-producing Enterobacter cloacae in the United Arab Emirates. Clin. Microbiol. Infect. 18:E494–E496.
    62.
    Sonnevend A, Al Baloushi A, Pal T, Hashmey R, Tariq WZ, Girgis S, Sheikh F, Pitout M, Hamadeh MB, Ghazawi A, and Al Haj M. 2012. Emergence of NDM-1 carbapenemase producing Enterobacteriaceae in Abu Dhabi Emirate, United Arab Emirates, abstr P1708. Abstr. 22nd Eur. Congr. Clin. Microbiol. Infect. Dis., London, United Kingdom.
    63.
    Mugnier P, Poirel L, Pitout M, and Nordmann P. 2008. Carbapenem-resistant and OXA-23-producing Acinetobacter baumannii isolates in the United Arab Emirates. Clin. Microbiol. Infect. 14:879–882.
    64.
    Opazo AF, Lopes B, Sonnevend A, Pal T, Ghazawi A, and Amyes SGB. 2011. Ceftazidime Resistance in Acinetobacter baumannii from the United Arab Emirates. Abstr. 51st Intersci. Conf. Antimicrob. Agents Chemother., Chicago, IL. http://www.icaac.org/.
    65.
    Ghazawi A, Sonnevend A, Bonnin RA, Poirel L, Nordmann P, Hashmey R, Rizvi TA, M BH, and Pal T. 2012. NDM-2 carbapenemase-producing Acinetobacter baumannii in the United Arab Emirates. Clin. Microbiol. Infect. 18:E34–E36.
    66.
    Jamal WY, Rotimi VO, Chugh TD, and Pal T. 1998. Prevalence and susceptibility of Shigella species to 11 antibiotics in a Kuwait teaching hospital. J. Chemother. 10:285–290.
    67.
    Jamal WY, Pal T, Rotimi VO, and Chugh TD. 1998. Serogroups and antimicrobial susceptibility of clinical isolates of Salmonella species from a teaching hospital in Kuwait. J. Diarrhoeal Dis. Res. 16:180–186.
    68.
    Jamal WY, El-Din K, Rotimi VO, and Chugh TD. 1999. An analysis of hospital-acquired bacteraemia in intensive care unit patients in a university hospital in Kuwait. J. Hosp. Infect. 43:49–56.
    69.
    Dimitrov TS, Udo EE, Emara M, Awni F, and Passadilla R. 2004. Etiology and antibiotic susceptibility patterns of community-acquired urinary tract infections in a Kuwait hospital. Med. Princ. Pract. 13:334–339.
    70.
    Jamal W, Rotimi VO, Khodakhast F, Saleem R, Pazhoor A, and Al Hashim G. 2005. Prevalence of extended-spectrum beta-lactamases in Enterobacteriaceae, Pseudomonas and Stenotrophomonas as determined by the VITEK 2 and E test systems in a Kuwait teaching hospital. Med. Princ. Pract. 14:325–331.
    71.
    Mokaddas EM, Shetty SA, Abdullah AA, and Rotimi VO. 2011. A 4-year prospective study of septicemia in pediatric surgical patients at a tertiary care teaching hospital in Kuwait. J. Pediatr. Surg. 46:679–684.
    72.
    Al Benwan K, Al Sweih N, and Rotimi VO. 2010. Etiology and antibiotic susceptibility patterns of community- and hospital-acquired urinary tract infections in a general hospital in Kuwait. Med. Princ. Pract. 19:440–446.
    73.
    Mokaddas EM, Abdulla AA, Shati S, and Rotimi VO. 2008. The technical aspects and clinical significance of detecting extended-spectrum beta-lactamase-producing Enterobacteriaceae at a tertiary-care hospital in Kuwait. J. Chemother. 20:445–451.
    74.
    Jamal WY, Al Hashem G, Khodakhast F, and Rotimi VO. 2009. Comparative in vitro activity of tigecycline and nine other antibiotics against gram-negative bacterial isolates, including ESBL-producing strains. J. Chemother. 21:261–266.
    75.
    Al Sweih N, Al Hashem G, Jamal W, and Rotimi V. 2010. National surveillance of antimicrobial susceptibility of CTX-M-positive and -negative clinical isolates of Escherichia coli from Kuwait government hospitals. J. Chemother. 22:254–258.
    76.
    Ensor VM, Jamal W, Rotimi VO, Evans JT, and Hawkey PM. 2009. Predominance of CTX-M-15 extended spectrum beta-lactamases in diverse Escherichia coli and Klebsiella pneumoniae from hospital and community patients in Kuwait. Int. J. Antimicrob. Agents 33:487–489.
    77.
    Al Hashem G, Al Sweih N, Jamal W, and Rotimi VO. 2011. Sequence analysis of blaCTX-M genes carried by clinically significant Escherichia coli isolates in Kuwait hospitals. Med. Princ. Pract. 20:213–219.
    78.
    Rogers BA, Sidjabat HE, and Paterson DL. 2011. Escherichia coli O25b-ST131: a pandemic, multiresistant, community-associated strain. J. Antimicrob. Chemother. 66:1–14.
    79.
    Coque TM, Novais A, Carattoli A, Poirel L, Pitout J, Peixe L, Baquero F, Canton R, and Nordmann P. 2008. Dissemination of clonally related Escherichia coli strains expressing extended-spectrum beta-lactamase CTX-M-15. Emerg. Infect. Dis. 14:195–200.
    80.
    Dashti AA, Vali L, Jadaon MM, El-Shazly S, and Amyes SG. 2011 The emergence of carbapenem resistance in ESBL-producing Escherichia coli O25B-ST131 strain from community acquired infection in Kuwait, abstr O27. Abstr. 1st Int. Conf. Prev. Infect. Control, Geneva, Switzerland.
    81.
    Vali L, Dashti AA, Jadaon MM, El-Shazly S, and Jose BT. 2011. First report of qnrA isolated from extended spectrum β-lactamase producing hospital-acquired Klebsiella pneumoniae in Kuwait, abstr P139. Abstr. 1st Int. Conf. Prev. Infect. Control, Geneva, Switzerland.
    82.
    Al Sweih N, Salama MF, Jamal W, Al Hashem G, and Rotimi VO. 2011. An outbreak of CTX-M-15-producing Klebsiella pneumoniae isolates in an intensive care unit of a teaching hospital in Kuwait. Indian J. Med. Microbiol. 29:130–135.
    83.
    Dashti AA, Jadaon MM, and Amyes SG. 2010. Retrospective study of an outbreak in a Kuwaiti hospital of multidrug-resistant Klebsiella pneumoniae possessing the new SHV-112 extended-spectrum beta-lactamase. J. Chemother. 22:335–338.
    84.
    Dashti AA, Jadaon MM, Gomaa HH, Noronha B, and Udo EE. 2010. Transmission of a Klebsiella pneumoniae clone harbouring genes for CTX-M-15-like and SHV-112 enzymes in a neonatal intensive care unit of a Kuwaiti hospital. J. Med. Microbiol. 59:687–692.
    85.
    Veras DL, Alves LC, Brayner FA, Guedes DR, Maciel MA, Rocha CR, and de Souza Lopes AC. 2011. Prevalence of the blaSHV gene in Klebsiella pneumoniae isolates obtained from hospital and community infections and from the microbiota of healthy individuals in Recife, Brazil. Curr. Microbiol. 62:1610–1616.
    86.
    Poirel L, Rotimi VO, Mokaddas EM, Karim A, and Nordmann P. 2001. VEB-1-like extended-spectrum beta-lactamases in Pseudomonas aeruginosa, Kuwait. Emerg. Infect. Dis. 7:468–470.
    87.
    Jamal W, Rotimi VO, Albert MJ, Khodakhast F, Udo EE, and Poirel L. 2012. Emergence of nosocomial New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae in patients admitted to a tertiary care hospital in Kuwait. Int. J. Antimicrob. Agents 39:183–184.
    88.
    Poirel L, Carbonnelle E, Bernabeu S, Gutmann L, Rotimi V, and Nordmann P. 2012. Importation of OXA-48-producing Klebsiella pneumoniae from Kuwait. J. Antimicrob. Chemother. 67:2051–2052.
    89.
    Mokaddas EM and Sanyal SC. 1999. Resistance patterns of Pseudomonas aeruginosa to carbapenems and piperacillin/tazobactam. J. Chemother. 11:93–96.
    90.
    Mokaddas E, Rotimi VO, and Sanyal SC. 1998. In vitro activity of piperacillin/tazobactam versus other broad-spectrum antibiotics against nosocomial gram-negative pathogens isolated from burn patients. J. Chemother. 10:208–214.
    91.
    Al-Sweih NA, Al-Hubail MA, and Rotimi VO. 2011. Emergence of tigecycline and colistin resistance in Acinetobacter species isolated from patients in Kuwait hospitals. J. Chemother. 23:13–16.
    92.
    Jamal W, Salama M, Dehrab N, Al Hashem G, Shahin M, and Rotimi VO. 2009. Role of tigecycline in the control of a carbapenem-resistant Acinetobacter baumannii outbreak in an intensive care unit. J. Hosp. Infect. 72:234–242.
    93.
    Afzal-Shah M, Woodford N, and Livermore DM. 2001. Characterization of OXA-25, OXA-26, and OXA-27, molecular class D beta-lactamases associated with carbapenem resistance in clinical isolates of Acinetobacter baumannii. Antimicrob. Agents Chemother. 45:583–588.
    94.
    Coelho J, Woodford N, Afzal-Shah M, and Livermore D. 2006. Occurrence of OXA-58-like carbapenemases in Acinetobacter spp. collected over 10 years in three continents. Antimicrob. Agents Chemother. 50:756–758.
    95.
    Mugnier PD, Bindayna KM, Poirel L, and Nordmann P. 2009. Diversity of plasmid-mediated carbapenem-hydrolysing oxacillinases among carbapenem-resistant Acinetobacter baumannii isolates from Kingdom of Bahrain. J. Antimicrob. Chemother. 63:1071–1073.
    96.
    Zarrilli R, Vitale D, Di Popolo A, Bagattini M, Daoud Z, Khan AU, Afif C, and Triassi M. 2008. A plasmid-borne blaOXA-58 gene confers imipenem resistance to Acinetobacter baumannii isolates from a Lebanese hospital. Antimicrob. Agents Chemother. 52:4115–4120.
    97.
    Rafay AM, Al-Muharrmi Z, and Toki R. 2007. Prevalence of extended-spectrum beta-lactamases-producing isolates over a 1-year period at a University Hospital in Oman. Saudi Med. J. 28:22–27.
    98.
    Al Muharrmi Z, Rafay AM, Balkhair A, Al-Tamemi S, Al Mawali A, and Al Sadiri H. 2008. Extended-spectrum β-lactamase (ESBL) in Omani children: study of prevalence, risk factors and clinical outcomes at Sultan Qaboos University Hospital, Sultanate of Oman. Sultan Qaboos Univ. Med. J. 8:171.
    99.
    Potron A, Poirel L, Elhag K, Al Yaqoubi F, and Nordmann P. 2009. VEB-6 extended-spectrum beta-lactamase-producing Proteus mirabilis from Sultanate of Oman. Int. J. Antimicrob. Agents 34:493–494.
    100.
    Ghosh K, Shenoy AK, and Al-Mahrooqi Z. 2002. Bacteriological infections during the first hundred days of allogenic bone marrow transplantation—experience from Oman. J. Assoc. Physicians India 50:910–912.
    101.
    Prakash KP, Arora V, and Geethanjali PP. 2011. Bloodstream bacterial pathogens and their antibiotic resistance pattern in Dhahira Region, Oman. Oman Med. J. 26:240–279.
    102.
    Poirel L, Al Maskari Z, Al Rashdi F, Bernabeu S, and Nordmann P. 2011. NDM-1-producing Klebsiella pneumoniae isolated in the Sultanate of Oman. J. Antimicrob. Chemother. 66:304–306.
    103.
    Potron A, Nordmann P, Lafeuille E, Al Maskari Z, Al Rashdi F, and Poirel L. 2011. Characterization of OXA-181, a carbapenem-hydrolyzing class D β-lactamase from Klebsiella pneumoniae. Antimicrob. Agents Chemother. 55:4896–4899.
    104.
    Pfeifer Y, Witte W, Al Maskari Z, Al Jardani A, Al Busaidy S, and Abdullah Al Balushi L. 2012. Characterisation of multidrug-resistant Enterobacteriaceae producing NDM-1 and OXA-48 carbapenemases from Oman, abstr R2516. Abstr. 22nd Eur. Congr. Clin. Microbiol. Infect. Dis., London, United Kingdom.
    105.
    Dortet L, Poirel L, Al Yaqoubi F, and Nordmann P. 2012. NDM-1, OXA-48 and OXA-181 carbapenemase-producing Enterobacteriaceae in Sultanate of Oman. Clin. Microbiol. Infect. 18:E144–E148.
    106.
    Al-Yaqoubi M and Elhag K. 2008. Susceptibilities of common bacterial isolates from Oman to old and new antibiotics. Oman Med. J. 23:173–178.
    107.
    Uwaydah AK, Matar I, Chacko KC, and Davidson JC. 1991. The emergence of antimicrobial resistant Salmonella typhi in Qatar: epidemiology and therapeutic implications. Trans. R. Soc. Trop. Med. Hyg. 85:790–792.
    108.
    El-Said MF, Bessisso MS, Janahi MA, Habob LH, and El-Shafie SS. 2002. Epidemiology of neonatal meningitis in Qatar. Saudi Med. J. 23:789–792.
    109.
    El Shafie S, Mohsin Z, Mohsin T, and Al Soub H. 2005. Antibiotic resistance pattern among aerobic Gram negative bacilli isolated from patients in intensive care units. Qatar Med. J. 14:29–33.
    110.
    Khan FY, Elshafie SS, Almaslamani M, Abu-Khattab M, El Hiday AH, Errayes M, and Almaslamani E. 2010. Epidemiology of bacteraemia in Hamad general hospital, Qatar: a one year hospital-based study. Travel Med. Infect. Dis. 8:377–387.
    111.
    El Shafie SS, Alishaq M, and Leni Garcia M. 2004. Investigation of an outbreak of multidrug-resistant Acinetobacter baumannii in trauma intensive care unit. J. Hosp. Infect. 56:101–105.
    112.
    Wallace MR, Johnson AP, Daniel M, Malde M, and Yousif AA. 1995. Sequential emergence of multi-resistant Klebsiella pneumoniae in Bahrain. J. Hosp. Infect. 31:247–252.
    113.
    Cookson B, Johnson AP, Azadian B, Paul J, Hutchinson G, Kaufmann M, Woodford N, Malde M, Walsh B, Yousif A, and Selkon J. 1995. International inter- and intrahospital patient spread of a multiple antibiotic-resistant strain of Klebsiella pneumoniae. J. Infect. Dis. 171:511–513.
    114.
    Bindayna KM, Senok AC, and Jamsheer AE. 2009. Prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae in Bahrain. J. Infect. Public Health 2:129–135.
    115.
    Bindayna KM and Ahmed RM. 2009. Microbial profile and antibiotic sensitivities of gram-negative rods in a neonatal intensive care unit. J. Bahrain Med. Soc. 21:344–348.
    116.
    Kapiszewski A. 2006. Arab versus Asian migrant workers in the GCC countries, UN/POP/EGM/2006/02. United Nations Expert Group Meeting on International Migration and Development in the Arab Region, Beirut, Lebanon.
    117.
    Lahlaoui H, Poirel L, Moussa MB, Ferjani M, Omrane B, and Nordmann P. 2011. Nosocomial dissemination of extended-spectrum beta-lactamase VEB-1a-producing Providencia stuartii isolates in a Tunisian hospital. Eur. J. Clin. Microbiol. Infect. Dis. 30:1267–1270.
    118.
    Aubert D, Naas T, Lartigue MF, and Nordmann P. 2005. Novel genetic structure associated with an extended-spectrum beta-lactamase blaVEB gene in a Providencia stuartii clinical isolate from Algeria. Antimicrob. Agents Chemother. 49:3590–3592.
    119.
    Lu PL, Doumith M, Livermore DM, Chen TP, and Woodford N. 2009. Diversity of carbapenem resistance mechanisms in Acinetobacter baumannii from a Taiwan hospital: spread of plasmid-borne OXA-72 carbapenemase. J. Antimicrob. Chemother. 63:641–647.
    120.
    Lee K, Kim MN, Choi TY, Cho SE, Lee S, Whang DH, Yong D, Chong Y, Woodford N, and Livermore DM. 2009. Wide dissemination of OXA-type carbapenemases in clinical Acinetobacter spp. isolates from South Korea. Int. J. Antimicrob. Agents 33:520–524.
    121.
    Wang H, Guo P, Sun H, Yang Q, Chen M, Xu Y, and Zhu Y. 2007. Molecular epidemiology of clinical isolates of carbapenem-resistant Acinetobacter spp. from Chinese hospitals. Antimicrob. Agents Chemother. 51:4022–4028.
    122.
    Tian GB, Adams-Haduch JM, Bogdanovich T, Pasculle AW, Quinn JP, Wang HN, and Doi Y. 2011. Identification of diverse OXA-40 group carbapenemases, including a novel variant, OXA-160, from Acinetobacter baumannii in Pennsylvania. Antimicrob. Agents Chemother. 55:429–432.
    123.
    Werneck JS, Picao RC, Carvalhaes CG, Cardoso JP, and Gales AC. 2011. OXA-72-producing Acinetobacter baumannii in Brazil: a case report. J. Antimicrob. Chemother. 66:452–454.
    124.
    Mugnier PD, Poirel L, Naas T, and Nordmann P. 2010. Worldwide dissemination of the blaOXA-23 carbapenemase gene of Acinetobacter baumannii. Emerg. Infect. Dis. 16:35–40.
    125.
    Ho PL, Lo WU, Yeung MK, Lin CH, Chow KH, Ang I, Tong AH, Bao JY, Lok S, and Lo JY. 2011. Complete sequencing of pNDM-HK encoding NDM-1 carbapenemase from a multidrug-resistant Escherichia coli strain isolated in Hong Kong. PLoS One 6:e17989.
    126.
    Nordmann P, Poirel L, Toleman MA, and Walsh TR. 2011. Does broad-spectrum beta-lactam resistance due to NDM-1 herald the end of the antibiotic era for treatment of infections caused by Gram-negative bacteria? J. Antimicrob. Chemother. 66:689–692.
    127.
    Walsh TR. 2008. Clinically significant carbapenemases: an update. Curr. Opin. Infect. Dis. 21:367–371.
    128.
    Bukhary Z, Mahmood W, Al-Khani A, and Al-Abdely HM. 2005. Treatment of nosocomial meningitis due to a multidrug resistant Acinetobacter baumannii with intraventricular colistin. Saudi Med. J. 26:656–658.
    129.
    Cunha BA. 2009. Pharmacokinetic considerations regarding tigecycline for multidrug-resistant (MDR) Klebsiella pneumoniae or MDR Acinetobacter baumannii urosepsis. J. Clin. Microbiol. 47:1613.
    130.
    Curcio D. 2008. Treatment of recurrent urosepsis with tigecycline: a pharmacological perspective. J. Clin. Microbiol. 46:1892–1893.
    131.
    Garonzik SM, Li J, Thamlikitkul V, Paterson DL, Shoham S, Jacob J, Silveira FP, Forrest A, and Nation RL. 2011. Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multi-center study provide dosing suggestions for various categories of patients. Antimicrob. Agents Chemother. 55:3284–3294.
    132.
    Lim LM, Ly N, Anderson D, Yang JC, Macander L, Jarkowski A III, Forrest A, Bulitta JB, and Tsuji BT. 2010. Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy 30:1279–1291.
    133.
    Ahmed KZ and Al-Saadi AR. 2005. A survey of multiple prescriptions dispensed in Saudi Arabia. Pak J. Pharm. Sci. 18:1–2.
    134.
    Irshaid YM, Al-Homrany MA, Hamdi AA, Adjepon-Yamoah KK, and Mahfouz AA. 2004. A pharmacoepidemiological study of prescription pattern in outpatient clinics in southwestern Saudi Arabia. Saudi Med. J. 25:1864–1870.
    135.
    Hanssens Y, Ismaeil BB, Kamha AA, Elshafie SS, Adheir FS, Saleh TM, and Deleu D. 2005. Antibiotic prescribing pattern in a medical intensive care unit in Qatar. Saudi Med. J. 26:1269–1276.
    136.
    Balkhy H, El-Saed A, and Jabri F. 2011. Antimicrobial consumption in four different adult intensive care units in a Saudi tertiary care hospital, abstr. P5. Abstr. 12th Congr. Int. Fed. Infect. Control, Venice, Italy.
    137.
    Centers for Disease Control and Prevention. 2004. National Nosocomial Infections Surveillance (NNIS) system report, data summary from January 1992 through June 2004, issued October 2004. Am. J. Infect. Control 32:470–485.
    138.
    Vojtova V, Kolar M, Hricova K, Uvizl R, Neiser J, Blahut L, and Urbanek K. 2011. Antibiotic utilization and Pseudomonas aeruginosa resistance in intensive care units. New Microbiol. 34:291–298.
    139.
    Jacoby TS, Kuchenbecker RS, Dos Santos RP, Magedanz L, Guzatto P, and Moreira LB. 2010. Impact of hospital-wide infection rate, invasive procedures use and antimicrobial consumption on bacterial resistance inside an intensive care unit. J. Hosp. Infect. 75:23–27.
    140.
    Morgan DJ, Okeke IN, Laxminarayan R, Perencevich EN, and Weisenberg S. 2011. Non-prescription antimicrobial use worldwide: a systematic review. Lancet Infect. Dis. 11:692–701.
    141.
    Al-Ghamdi MS. 2001. Empirical treatment of uncomplicated urinary tract infection by community pharmacists in the eastern province of Saudi Arabia. Saudi Med. J. 22:1105–1108.
    142.
    Bin Abdulhak AA, Altannir MA, Almansor MA, Almohaya MS, Onazi AS, Marei MA, Aldossary OF, Obeidat SA, Obeidat MA, Riaz MS, and Tleyjeh IM. 2011. Non prescribed sale of antibiotics in Riyadh, Saudi Arabia: a cross sectional study. BMC Public Health 11:538.
    143.
    Dameh M, Green J, and Norris P. 2010. Over-the-counter sales of antibiotics from community pharmacies in Abu Dhabi. Pharm. World Sci. 32:643–650.
    144.
    Al-Ghamdi MS, Al-Mustafa ZH, El-Morsy F, Al-Faky A, Haider I, and Essa H. 2000. Residues of tetracycline compounds in poultry products in the eastern province of Saudi Arabia. Public Health 114:300–304.
    145.
    Al-Mustafa ZH and Al-Ghamdi MS. 2000. Use of norfloxacin in poultry production in the eastern province of Saudi Arabia and its possible impact on public health. Int. J. Environ. Health Res. 10:291–299.
    146.
    Al-Ghamdi MS, El-Morsy F, Al-Mustafa ZH, Al-Ramadhan M, and Hanif M. 1999. Antibiotic resistance of Escherichia coli isolated from poultry workers, patients and chicken in the eastern province of Saudi Arabia. Trop. Med. Int. Health 4:278–283.
    147.
    Bazile-Pham-Khac S, Truong QC, Lafont JP, Gutmann L, Zhou XY, Osman M, and Moreau NJ. 1996. Resistance to fluoroquinolones in Escherichia coli isolated from poultry. Antimicrob. Agents Chemother. 40:1504–1507.
    148.
    Al-Zenki S, Al-Nasser A, Al-Safar A, Alomirah H, Al-Haddad A, Hendriksen RS, and Aarestrup FM. 2007. Prevalence and antibiotic resistance of Salmonella isolated from a poultry farm and processing plant environment in the State of Kuwait. Foodborne Pathog. Dis. 4:367–373.
    149.
    Altalhi AD, Gherbawy YA, and Hassan SA. 2010. Antibiotic resistance in Escherichia coli isolated from retail raw chicken meat in Taif, Saudi Arabia. Foodborne Pathog. Dis. 7:281–285.
    150.
    Basurrah MM and Madani TA. 2006. Handwashing and gloving practice among health care workers in medical and surgical wards in a tertiary care centre in Riyadh, Saudi Arabia. Scand. J. Infect. Dis. 38:620–624.
    151.
    Al-Wazzan B, Salmeen Y, Al-Amiri E, Abul A, Bouhaimed M, and Al-Taiar A. 2011. Hand hygiene practices among nursing staff in public secondary care hospitals in Kuwait: self-report and direct observation. Med. Princ. Pract. 20:326–331.
    152.
    Bukhari SZ, Hussain WM, Banjar A, Almaimani WH, Karima TM, and Fatani MI. 2011. Hand hygiene compliance rate among healthcare professionals. Saudi Med. J. 32:515–519.
    153.
    Ahmed QA, Memish ZA, Allegranzi B, and Pittet D. 2006. Muslim health-care workers and alcohol-based handrubs. Lancet 367:1025–1027.
    154.
    Allegranzi B, Memish ZA, Donaldson L, and Pittet D. 2009. Religion and culture: potential undercurrents influencing hand hygiene promotion in health care. Am. J. Infect. Control 37:28–34.
    155.
    Al-Bahry SN, Mahmoud IY, Al-Belushi KI, Elshafie AE, Al-Harthy A, and Bakheit CK. 2009. Coastal sewage discharge and its impact on fish with reference to antibiotic resistant enteric bacteria and enteric pathogens as bio-indicators of pollution. Chemosphere 77:1534–1539.
    156.
    Qureshi AA and Qureshi MA. 1992. Multiple antibiotic resistant fecal coliforms in raw sewage. Water Air Soil Pollut. 61:47–56.
    157.
    Walsh TR, Weeks J, Livermore DM, and Toleman MA. 2011. Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study. Lancet Infect. Dis. 11:355–362.
    158.
    Hassan SA, Altalhi AD, Gherbawy YA, and El-Deeb BA. 2011. Bacterial load of fresh vegetables and their resistance to the currently used antibiotics in Saudi Arabia. Foodborne Pathog. Dis. 8:1011–1018.
    159.
    Korenyi-Both AL, Molnar AC, and Fidelus-Gort R. 1992. Al Eskan disease: Desert Storm pneumonitis. Mil. Med. 157:452–462.
    160.
    Kellogg CA and Griffin DW. 2006. Aerobiology and the global transport of desert dust. Trends Ecol. Evol. 21:638–644.
    161.
    Al-Bahry S, Mahmoud I, Elshafie A, Al-Harthy A, Al-Ghafri S, Al-Amri I, and Alkindi A. 2009. Bacterial flora and antibiotic resistance from eggs of green turtles Chelonia mydas: an indication of polluted effluents. Mar. Pollut. Bull. 58:720–725.
    162.
    Al-Bahry SN, Mahmoud IY, Al-Zadjali M, Elshafie A, Al-Harthy A, and Al-Alawi W. 2011. Antibiotic resistant bacteria as bio-indicator of polluted effluent in the green turtles, Chelonia mydas in Oman. Mar. Environ. Res. 71:139–144.
    163.
    Wilson ME. 2003. The traveller and emerging infections: sentinel, courier, transmitter. J. Appl. Microbiol. 94(Suppl):1S–11S.
    164.
    Memish ZA, Venkatesh S, and Shibl AM. 2003. Impact of travel on international spread of antimicrobial resistance. Int. J. Antimicrob. Agents 21:135–142.
    165.
    Rogers BA, Aminzadeh Z, Hayashi Y, and Paterson DL. 2011. Country-to-country transfer of patients and the risk of multi-resistant bacterial infection. Clin. Infect. Dis. 53:49–56.
    166.
    Al-Hinai SS, Al-Busaidi AS, and Al-Busaidi IH. 2011. Medical tourism abroad: a new challenge to Oman's health system—Al Dakhilya region experience. Sultan Qaboos Univ. Med. J. 11:477–484.
    167.
    Baby Padmini S, Appala Raju B, and Mani KR. 2008. Detection of Enterobacteriaceae producing CTX-M extended spectrum beta-lactamases from a tertiary care hospital in south India. Indian J. Med. Microbiol. 26:163–166.
    168.
    Doi Y, Adams-Haduch JM, Shivannavar CT, Paterson DL, and Gaddad SM. 2009. Faecal carriage of CTX-M-15-producing Klebsiella pneumoniae in patients with acute gastroenteritis. Indian J. Med. Res. 129:599–602.
    169.
    Ensor VM, Shahid M, Evans JT, and Hawkey PM. 2006. Occurrence, prevalence and genetic environment of CTX-M beta-lactamases in Enterobacteriaceae from Indian hospitals. J. Antimicrob. Chemother. 58:1260–1263.
    170.
    Freeman JT, McBride SJ, Heffernan H, Bathgate T, Pope C, and Ellis-Pegler RB. 2008. Community-onset genitourinary tract infection due to CTX-M-15-Producing Escherichia coli among travelers to the Indian subcontinent in New Zealand. Clin. Infect. Dis. 47:689–692.
    171.
    Muzaheed, Doi Y, Adams-Haduch JM, Endimiani A, Sidjabat HE, Gaddad SM, and Paterson DL. 2008. High prevalence of CTX-M-15-producing Klebsiella pneumoniae among inpatients and outpatients with urinary tract infection in Southern India. J. Antimicrob. Chemother. 61:1393–1394.
    172.
    Memish ZA. 2010. The Hajj: communicable and non-communicable health hazards and current guidance for pilgrims. Euro Surveill. 15:19671.
    173.
    Ahmed QA, Arabi YM, and Memish ZA. 2006. Health risks at the Hajj. Lancet 367:1008–1015.
    174.
    Al-Ghamdi SM, Akbar HO, Qari YA, Fathaldin OA, and Al-Rashed RS. 2003. Pattern of admission to hospitals during Muslim pilgrimage (Hajj). Saudi Med. J. 24:1073–1076.
    175.
    Bukhari SZ, Hussain WM, Fatani MI, and Ashshi AM. 2008. Multi-drug resistant Ewingella americana. Saudi Med. J. 29:1051–1053.
    176.
    Asghar AH and Faidah HS. 2009. Frequency and antimicrobial susceptibility of gram-negative bacteria isolated from 2 hospitals in Makkah, Saudi Arabia. Saudi Med. J. 30:1017–1023.
    177.
    Asghar AH. 2006. Frequency and antimicrobial susceptibility patterns of bacterial pathogens isolated from septicemic patients in Makkah hospitals. Saudi Med. J. 27:361–367.
    178.
    O'Brien TF and Stelling J. 2011. Integrated multilevel surveillance of the world's infecting microbes and their resistance to antimicrobial agents. Clin. Microbiol. Rev. 24:281–295.
    179.
    Wilson G, Badarudeen S, and Godwin A. 2010. Real-time validation and presentation of the cumulative antibiogram and implications of presenting a standard format using a novel in-house software: ABSOFT. Am. J. Infect. Control 38:e25–e30.
    180.
    Memish ZA and Shibl AM. 2011. Consensus building and recommendations based on the available epidemiology of meningococcal disease in Gulf Cooperation Council states. Travel Med. Infect. Dis. 9:60–66.
    181.
    Memish ZA, Ahmed QA, Arabi YM, Shibl AM, and Niederman MS. 2007. Microbiology of community-acquired pneumonia in the Gulf Corporation Council states. J. Chemother. 19(Suppl 1):17–23.
    182.
    Aly M and Balkhy HH. 2012. The prevalence of antimicrobial resistance in clinical isolates from Gulf Corporation Council countries. Antimicrob. Resist. Infect. Control 1:26.
    183.
    Al-Tawfiq JA, Stephens G, and Memish ZA. 2010. Inappropriate antimicrobial use and potential solutions: a Middle Eastern perspective. Expert Rev. Anti Infect. Ther. 8:765–774.
    184.
    Ohl CA and Dodds Ashley ES. 2011. Antimicrobial stewardship programs in community hospitals: the evidence base and case studies. Clin. Infect. Dis. 53(Suppl 1):S23–S30.
    185.
    Hammerum AM, Heuer OE, Lester CH, Agerso Y, Seyfarth AM, Emborg HD, Frimodt-Moller N, and Monnet DL. 2007. Comment on: withdrawal of growth-promoting antibiotics in Europe and its effects in relation to human health. Int. J. Antimicrob. Agents 30:466–468.
    186.
    Phillips I. 2007. Withdrawal of growth-promoting antibiotics in Europe and its effects in relation to human health. Int. J. Antimicrob. Agents 30:101–107.
    187.
    Nordmann P, Poirel L, Carrer A, Toleman MA, and Walsh TR. 2011. How to detect NDM-1 producers. J. Clin. Microbiol. 49:718–721.
    188.
    Poirel L, Potron A, and Nordmann P. 2012. OXA-48-like carbapenemases: the phantom menace. J. Antimicrob. Chemother. 67:1597–1606.
    189.
    Hrabak J, Chudackova E, and Walkova R. 2013. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry for detection of antibiotic resistance mechanisms: from research to routine diagnosis. Clin. Microbiol. Rev. 26:103–114.
    190.
    Almaraghi N, Dashti A, Hamouda A, and Amyes S. 2011. Characterization of incFIA, incFIB, and incN plasmid carrying CTX-M-3, -15, -55 β-lactamases from Escherichia coli and Klebsiella pneumoniea strains from 5 major Kuwaiti hospitals. Abstr. 51st Intersci. Conf. Antimicrob. Agents Chemother., Chicago, IL. http://www.icaac.org/.
    191.
    Somily AM, Absar MM, Arshad MZ, Al Aska AI, Shakoor ZA, Fatani AJ, Siddiqui YM, and Murray TS. 2012. Antimicrobial susceptibility patterns of multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii against carbapenems, colistin, and tigecycline. Saudi Med. J. 33:750–755.

    Author Bios

    Hosam M. Zowawi [email protected]
    The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
    King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
    Hosam M. Zowawi is currently a Ph.D. candidate at The University of Queensland Centre for Clinical Research (UQCCR). He is also affiliated with King Saud bin Abdulaziz University for Health Science, National Guard-Health Affairs, in Riyadh, Saudi Arabia. In 2010, he completed his master's degree in clinical microbiology with honors from Griffith University and completed his dissertation at the Queensland Institute of Medical Research. His Ph.D. dissertation work focuses on the β-lactamase-producing Gram-negative bacilli isolated from hospitals in the Gulf Cooperation Council states. He is also developing innovative diagnostic methods for rapid identification of antibiotic-resistant bacteria.
    Hanan H. Balkhy
    King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
    Hanan H. Balkhy is an Associate Professor of Pediatric Infectious Disease. She directs the World Health Organization Collaboration Center and the Gulf Cooperation Council Center for Infection Control as well as the Infection Prevention and Control Department at the National Guard-Health Affairs, Saudi Arabia. She received her medical training at King Abdulaziz University in Jeddah and completed her training at Massachusetts General Hospital in pediatrics and a pediatric infectious disease fellowship at the Cleveland Clinic Foundation and Case Western Reserve University Joint ID program.
    Timothy R. Walsh
    The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
    Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, United Kingdom
    Timothy R. Walsh is a Professor of Medical Microbiology and Antimicrobial Resistance at Cardiff University and an honorary professor and a theme leader at The University of Queensland Centre for Clinical Research (UQCCR). He completed his Ph.D. studying β-lactamases at Bristol University. His research focuses on unusual mechanisms of antimicrobial resistance and how they are mobilized into the clinical sector and spread once established. Enzymes that Professor Walsh and his team have discovered include SPM-1, VIM-7, GIM-1, OXA-45, AIM-1, and NDM-1.
    David L. Paterson
    The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
    David L. Paterson is a Professor of Medicine at The University of Queensland Centre for Clinical Research (UQCCR) as well as a Consultant Infectious Diseases Physician, Consultant Microbiologist, and Medical Advisor for the Centre for Healthcare Related Infection Surveillance and Prevention (CHRISP). He received his medical degree and Ph.D. from The University of Queensland. In 2007, he returned to Brisbane after spending 10 years at The University of Pittsburgh School of Medicine. His research interests include the study of the molecular and clinical epidemiology of infections with antibiotic-resistant organisms. The focus of this work is the translation of knowledge into optimal prevention and treatment of these infections.

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    Clinical Microbiology Reviews
    Volume 26Number 3July 2013
    Pages: 361 - 380

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    Hosam M. Zowawi [email protected]
    The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
    King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
    Hanan H. Balkhy
    King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
    Timothy R. Walsh
    The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
    Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, United Kingdom
    David L. Paterson
    The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia

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  • Clinical Microbiology ReviewsArticle
    Translating Recent Microbiome Insights in Otitis Media into Probiotic Strategies

    SUMMARY

    The microbiota of the upper respiratory tract (URT) protects the host from bacterial pathogenic colonization by competing for adherence to epithelial cells and by immune response regulation that includes the activation of antimicrobial and (anti-)inflammatory components. However, environmental or host factors can modify the microbiota to an unstable community that predisposes the host to infection or inflammation. One of the URT diseases most often encountered in children is otitis media (OM). The role of pathogenic bacteria like Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the pathogenesis of OM is well documented. Results from next-generation-sequencing (NGS) studies reveal other bacterial taxa involved in OM, such as Turicella and Alloiococcus. Such studies can also identify bacterial taxa that are potentially protective against URT infections, whose beneficial action needs to be substantiated in relevant experimental models and clinical trials. Of note, lactic acid bacteria (LAB) are members of the URT microbiota and associated with a URT ecosystem that is deemed healthy, based on NGS and some experimental and clinical studies. These observations have formed the basis of this review, in which we describe the current knowledge of the molecular and clinical potential of LAB in the URT, which is currently underexplored in microbiome and probiotic research.

    REFERENCES

    1.
    Man WH, de Steenhuijsen Piters WAA, Bogaert D. 2017. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat Rev Microbiol 15:259–270.
    2.
    Dhooge I, Desloovere C, Boudewyns A, Van Kempen M, Dachy JP. 2005. Management of otitis media with effusion in children. B-ENT 1(Suppl 1):3–13.
    3.
    Schilder AGM, Chonmaitree T, Cripps AW, Rosenfeld RM, Casselbrant ML, Haggard MP, Venekamp RP. 2016. Otitis media. Nat Rev Dis Primers 2:16063.
    4.
    Lieberthal AS, Carroll AE, Chonmaitree T, Ganiats TG, Hoberman A, Jackson MA, Joffe MD, Miller DT, Rosenfeld RM, Sevilla XD, Schwartz RH, Thomas PA, Tunkel DE. 2013. The diagnosis and management of acute otitis media. Pediatrics 131:e964–e999.
    5.
    Flynn T, Möller C, Jönsson R, Lohmander A. 2009. The high prevalence of otitis media with effusion in children with cleft lip and palate as compared to children without clefts. Int J Pediatr Otorhinolaryngol 73:1441–1446.
    6.
    Maris M, Wojciechowski M, Van de Heyning P, Boudewyns A. 2014. A cross-sectional analysis of otitis media with effusion in children with Down syndrome. Eur J Pediatr 173:1319–1325.
    7.
    Buzatto GP, Tamashiro E, Proenca-Modena JL, Saturno TH, Prates MC, Gagliardi TB, Carenzi LR, Massuda ET, Hyppolito MA, Valera FCP, Arruda E, Anselmo-Lima WT. 2017. The pathogens profile in children with otitis media with effusion and adenoid hypertrophy. PLoS One 12:e0171049.
    8.
    Rosenfeld RM, Bluestone CD. 2003. Clinical efficacy of surgical therapy, p 227–239. In Rosenfeld RM, Bluestone CD (ed), Evidence-based otitis media, 2nd ed. B. C. Decker, Hamilton, Ontario, Canada.
    9.
    Bluestone CD. 2003. Definitions, terminology, and classification, p 120–135. In Rosenfeld RM, Bluestone CD (ed), Evidence-based otitis media, 2nd ed. B. C. Decker, Hamilton, Ontario, Canada.
    10.
    Boudewyns A, Antunes J, Bernheim N, Claes J, De Dooy J, De Leenheer E, De Roeck K, Hellings P, de Varebeke SJ, Jorissen M, Ketelslagers K, Lemkens N, Lemkens P, Leupe P, Malfroot A, Maris M, Michiels E, Van Crombrugge L, Vandenplas Y, Verhulst S, Eloy P, Watelet JB. 2012. Specific medical and surgical treatment for chronic inflammatory diseases in children. B-ENT 8(Suppl 19):135–166.
    11.
    Verhoeff M, Van Der Veen EL, Rovers MM, Sanders EAM, Schilder A. 2006. Chronic suppurative otitis media: a review. Int J Pediatr Otorhinolaryngol 70:1–12.
    12.
    Rovers MM, Schilder AG, Zielhuis GA, Rosenfeld RM. 2004. Otitis media. Lancet 363:465–473.
    13.
    Chonmaitree T, Trujillo R, Jennings K, Alvarez-Fernandez P, Patel JA, Loeffelholz MJ, Nokso-Koivisto J, Matalon R, Pyles RB, Miller AL, McCormick DP. 2016. Acute otitis media and other complications of viral respiratory infection. Pediatrics 137:e20153555.
    14.
    Zielhuis GA, Heuvelmans-Heinen EW, Rach GH, Van Den Broek P. 1989. Environmental risk factors for otitis media with effusion in preschool children. Scand J Prim Health Care 7:33–38.
    15.
    Pettigrew MM, Laufer AS, Gent JF, Kong Y, Fennie KP, Metlay JP. 2012. Upper respiratory tract microbial communities, acute otitis media pathogens, and antibiotic use in healthy and sick children. Appl Environ Microbiol 78:6262–6270.
    16.
    Akkerman AE, Kuyvenhoven MM, van der Wouden JC, Verheij T. 2005. Analysis of under- and overprescribing of antibiotics in acute otitis media in general practice. J Antimicrob Chemother 56:569–574.
    17.
    Froom J, Culpepper L, Green LA, de Melker RA, Grob P, Heeren T, van Balen F. 2001. A cross-national study of acute otitis media: risk factors, severity, and treatment at initial visit. Report from the International Primary Care Network (IPCN) and the Ambulatory Sentinel Practice Network (ASPN). J Am Board Fam Pract 14:406–417.
    18.
    Venekamp RP, Sanders SL, Glasziou PP, Del Mar CB, Rovers MM. 2015. Antibiotics for acute otitis media in children. Cochrane Database Syst Rev 2015:CD000219.
    19.
    Venekamp RP, Burton MJ, van Dongen TM, van der Heijden GJ, van Zon A, Schilder AG. 2016. Antibiotics for otitis media with effusion in children. Cochrane Database Syst Rev 2016:CD009163.
    20.
    Chonmaitree T, Revai K, Grady JJ, Clos A, Patel JA, Nair S, Fan J, Henrickson KJ. 2008. Viral upper respiratory tract infection and otitis media complication in young children. Clin Infect Dis 46:815–823.
    21.
    Buchman CA, Doyle WJ, Skoner DP, Post JC, Alper CM, Seroky JT, Anderson K, Preston RA, Hayden FG, Fireman P, Ehrlich GD. 1995. Influenza A virus-induced acute otitis media. J Infect Dis 172:1348–1351.
    22.
    Bakaletz LO. 2010. Immunopathogenesis of polymicrobial otitis media. J Leukoc Biol 87:213–222.
    23.
    Revai K, Mamidi D, Chonmaitree T. 2008. Association of nasopharyngeal bacterial colonization during upper respiratory tract infection and the development of acute otitis media. Clin Infect Dis 46:e34–e37.
    24.
    Kaur R, Morris M, Pichichero ME. 2017. Epidemiology of acute otitis media in the postpneumococcal conjugate vaccine era. Pediatrics 140:20170181.
    25.
    Patel JA, Nguyen DT, Revai K, Chonmaitree T. 2007. Role of respiratory syncytial virus in acute otitis media: implications for vaccine development. Vaccine 25:1683–1689.
    26.
    Nokso-Koivisto J, Räty R, Blomqvist S, Kleemola M, Syrjänen R, Pitkäranta A, Kilpi T, Hovi T. 2004. Presence of specific viruses in the middle ear fluids and respiratory secretions of young children with acute otitis media. J Med Virol 72:241–248.
    27.
    Patel JA, Nair S, Revai K, Grady J, Chonmaitree T. 2009. Nasopharyngeal acute phase cytokines in viral upper respiratory infection: impact on acute otitis media in children. Pediatr Infect Dis J 28:1002–1007.
    28.
    Pittet LA, Hall-Stoodley L, Rutkowski MR, Harmsen AG. 2010. Influenza virus infection decreases tracheal mucociliary velocity and clearance of Streptococcus pneumoniae. Am J Respir Cell Mol Biol 42:450–460.
    29.
    Avadhanula V, Rodriguez CA, Devincenzo JP, Wang Y, Webby RJ, Ulett GC, Adderson EE. 2006. Respiratory viruses augment the adhesion of bacterial pathogens to respiratory epithelium in a viral species- and cell type-dependent manner. J Virol 80:1629–1636.
    30.
    Willner D, Haynes MR, Furlan M, Hanson N, Kirby B, Lim YW, Rainey PB, Schmieder R, Youle M, Conrad D, Rohwer F. 2012. Case studies of the spatial heterogeneity of DNA viruses in the cystic fibrosis lung. Am J Respir Cell Mol Biol 46:127–131.
    31.
    Willner D, Furlan M, Haynes M, Schmieder R, Angly FE, Silva J, Tammadoni S, Nosrat B, Conrad D, Rohwer F. 2009. Metagenomic analysis of respiratory tract DNA viral communities in cystic fibrosis and non-cystic fibrosis individuals. PLoS One 4:e7370.
    32.
    Yang J, Yang F, Ren L, Xiong Z, Wu Z, Dong J, Sun L, Zhang T, Hu Y, Du J, Wang J, Jin Q. 2011. Unbiased parallel detection of viral pathogens in clinical samples by use of a metagenomic approach. J Clin Microbiol 49:3463–3469.
    33.
    Lysholm F, Wetterbom A, Lindau C, Darban H, Bjerkner A, Fahlander K, Lindberg AM, Persson B, Allander T, Andersson B. 2012. Characterization of the viral microbiome in patients with severe lower respiratory tract infections, using metagenomic sequencing. PLoS One 7:e30875.
    34.
    Wang Y, Zhu N, Li Y, Lu R, Wang H, Liu G, Zou X, Xie Z, Tan W. 2016. Metagenomic analysis of viral genetic diversity in respiratory samples from children with severe acute respiratory infection in China. Clin Microbiol Infect 22:458.e1–458.e9.
    35.
    Zoll J, Rahamat-Langendoen J, Ahout I, de Jonge MI, Jans J, Huijnen MA, Ferwerda G, Warris A, Melchers WJ. 2015. Direct multiplexed whole genome sequencing of respiratory tract samples reveals full viral genomic information. J Clin Virol 66:6–11.
    36.
    Bokulich NA, Mills DA. 2013. Improved selection of internal transcribed spacer-specific primers enables quantitative, ultra-high-throughput profiling of fungal communities. Appl Environ Microbiol 79:2519–2526.
    37.
    Ngo CC, Massa HM, Thornton RB, Cripps AW. 2016. Predominant bacteria detected from the middle ear fluid of children experiencing otitis media: a systematic review. PLoS One 11:e0150949.
    38.
    Vandeputte D, Tito RY, Vanleeuwen R, Falony G, Raes J. 2017. Practical considerations for large-scale gut microbiome studies. FEMS Microbiol Rev 41(Supp_1):S154–S167.
    39.
    De Steenhuijsen Piters WAA, Sanders EAM, Bogaert D. 2015. The role of the local microbial ecosystem in respiratory health and disease. Philos Trans R Soc 370:20140294.
    40.
    Bosch A, Levin E, Van Houten MA, Hasrat R, Kalkman G, Biesbroek G, De Steenhuijsen Piters WAA, De Groot P-K, Pernet P, Keijser BJF, Sanders EAM, Bogaert D. 2016. Development of upper respiratory tract microbiota in infancy is affected by mode of delivery. EBioMedicine 9:336–345.
    41.
    Biesbroek G, Tsivtsivadze E, Sanders EAM, Montijn R, Veenhoven RH, Keijser BJF, Bogaert D. 2014. Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Am J Respir Crit Care Med 190:1283–1292.
    42.
    Biesbroek G, Bosch A, Wang X, Keijser BJF, Veenhoven RH, Sanders EAM, Bogaert D. 2014. The impact of breastfeeding on nasopharyngeal microbial communities in infants. Am J Respir Crit Care Med 190:298–308.
    43.
    Santee CA, Nagalingam NA, Faruqi AA, DeMuri GP, Gern JE, Wald ER, Lynch SV. 2016. Nasopharyngeal microbiota composition of children is related to the frequency of upper respiratory infection and acute sinusitis. Microbiome 4:34.
    44.
    Earl JP, de Vries SPW, Ahmed A, Powell E, Schultz MP, Hermans PWM, Hill DJ, Zhou Z, Constantinidou CI, Hu FZ, Bootsma HJ, Ehrlich GD. 2016. Comparative genomic analyses of the Moraxella catarrhalis serosensitive and seroresistant lineages demonstrate their independent evolution. Genome Biol Evol 8:955–974.
    45.
    Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. 2016. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods 13:581–583.
    46.
    Earl JP, Adappa ND, Krol J, Bhat AS, Balashov S, Ehrlich RL, Palmer JN, Workman AD, Blasetti M, Hammond J, Cohen NA, Ehrlich GD, Mell JC. 2018. Species-level bacterial community profiling of the healthy sinonasal microbiome using Pacific Biosciences sequencing of full-length 16S rRNA genes. bioRxiv doi:
    47.
    Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R. 2010. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A 107:11971–11975.
    48.
    Ton-That H, Schneewind O. 2003. Assembly of pili on the surface of Corynebacterium diphtheriae. Mol Microbiol 50:1429–1438.
    49.
    Tarr PE, Stock F, Cooke RH, Fedorko DP, Lucey DR. 2003. Multidrug-resistant Corynebacterium striatum pneumonia in a heart transplant recipient. Transpl Infect Dis 5:53–58.
    50.
    Ridaura VK, Bouladoux N, Claesen J, Chen YE, Byrd AL, Constantinides MG, Merrill ED, Tamoutounour S, Fischbach MA, Belkaid Y. 2018. Contextual control of skin immunity and inflammation by Corynebacterium. J Exp Med 215:785–799.
    51.
    De Boeck I, Wittouck S, Wuyts S, Oerlemans EFM, van den Broek MFL, Vandenheuvel D, Vanderveken O, Lebeer S. 2017. Comparing the healthy nose and nasopharynx microbiota reveals continuity as well as niche-specificity. Front Microbiol 8:2372.
    52.
    Teo SM, Mok D, Pham K, Kusel M, Serralha M, Troy N, Holt BJ, Hales BJ, Walker ML, Hollams E, Bochkov YA, Grindle K, Johnston SL, Gern JE, Sly PD, Holt PG, Holt KE, Inouye M. 2015. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe 17:704–715.
    53.
    Liu CM, Price LB, Hungate BA, Abraham AG, Larsen LA, Christensen K, Stegger M, Skov R, Andersen PS. 2015. Staphylococcus aureus and the ecology of the nasal microbiome. Sci Adv 1:e1400216.
    54.
    Santos-Cortez RLP, Chiong CM, Frank DN, Ryan AF, Giese APJ, Bootpetch Roberts T, Daly KA, Steritz MJ, Szeremeta W, Pedro M, Pine H, Yarza TKL, Scholes MA, Llanes EdV, Yousaf S, Friedman N, Tantoco MLC, Wine TM, Labra PJ, Benoit J, Ruiz AG, de la Cruz RAR, Greenlee C, Yousaf A, Cardwell J, Nonato RMA, Ray D, Ong KMC, So E, Robertson CE, Dinwiddie J, Lagrana-Villagracia SM, Gubbels SP, Shaikh RS, Cass SP, Einarsdottir E, Lee NR, Schwartz DA, Gloria-Cruz TLI, Bamshad MJ, Yang IV, Kere J, Abes GT, Prager JD, Riazuddin S, Chan AL, Yoon PJ, Nickerson DA, Cutiongco-de la Paz EM, Streubel SO, Reyes-Quintos MRT, Jenkins HA, et al. 2018. FUT2 variants confer susceptibility to familial otitis media. Am J Hum Genet 103:679–690.
    55.
    Mika M, Mack I, Korten I, Qi W, Aebi S, Frey U, Latzin P, Hilty M. 2015. Dynamics of the nasal microbiota in infancy: a prospective cohort study. J Allergy Clin Immunol 135:905–912.e11.
    56.
    Bogaert D, Keijser B, Huse S, Rossen J, Veenhoven R, van Gils E, Bruin J, Montijn R, Bonten M, Sanders E. 2011. Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis. PLoS One 6:e17035.
    57.
    Greenberg D, Givon-Lavi N, Broides A, Blancovich I, Peled N, Dagan R. 2006. The contribution of smoking and exposure to tobacco smoke to Streptococcus pneumoniae and Haemophilus influenzae carriage in children and their mothers. Clin Infect Dis 42:897–903.
    58.
    Man WH, van Dongen TMA, Venekamp RP, Pluimakers VG, Chu M, van Houten MA, Sanders EAM, Schilder AGM, Bogaert D. 2019. Respiratory microbiota predicts clinical disease course of acute otorrhea in children with tympanostomy tubes. Pediatr Infect Dis J 38:e116–e125.
    59.
    Laufer AS, Metlay JP, Gent JF, Fennie KP, Kong Y, Pettigrew MM. 2011. Microbial communities of the upper respiratory tract and otitis media in children. mBio 2:e00245-10.
    60.
    Hilty M, Qi W, Brugger SD, Frei L, Agyeman P, Frey PM, Aebi S, Mühlemann K. 2012. Nasopharyngeal microbiota in infants with acute otitis media. J Infect Dis 205:1048–1055.
    61.
    Sillanpää S, Kramna L, Oikarinen S, Sipilä M, Rautiainen M, Aittoniemi J, Laranne J, Hyöty H, Cinek O. 2017. Next-generation sequencing combined with specific PCR assays to determine the bacterial 16S rRNA gene profiles of middle ear fluid collected from children with acute otitis media. mSphere 2:e00006-17.
    62.
    Gomez-Garces JL, Alhambra A, Alos JI, Barrera B, García G. 2004. Acute and chronic otitis media and Turicella otitidis: a controversial association. Clin Microbiol Infect 10:854–857.
    63.
    Ashhurst-Smith C, Hall ST, Walker P, Stuart J, Hansbro PM, Blackwell CC. 2007. Isolation of Alloiococcus otitidis from Indigenous and non-Indigenous Australian children with chronic otitis media with effusion. FEMS Immunol Med Microbiol 51:163–170.
    64.
    Lappan R, Imbrogno K, Sikazwe C, Anderson D, Mok D, Coates H, Vijayasekaran S, Bumbak P, Blyth CC, Jamieson SE, Peacock CS. 2018. A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera. BMC Microbiol 18:13.
    65.
    Liu CM, Cosetti MK, Aziz M, Buchhagen JL, Contente-Cuomo TL, Price LB, Keim PS, Lalwani AK. 2011. The otologic microbiome: a study of the bacterial microbiota in a pediatric patient with chronic serous otitis media using 16S rRNA gene-based pyrosequencing. Arch Otolaryngol Head Neck Surg 137:664–668.
    66.
    Jervis-Bardy J, Rogers GB, Morris PS, Smith-Vaughan HC, Nosworthy E, Leong LEX, Smith RJ, Weyrich LS, De Haan J, Carney AS, Leach AJ, O’Leary S, Marsh RL. 2015. The microbiome of otitis media with effusion in Indigenous Australian children. Int J Pediatr Otorhinolaryngol 79:1548–1555.
    67.
    Chan CL, Wabnitz D, Bardy JJ, Bassiouni A, Wormald P-J, Vreugde S, Psaltis AJ. 2016. The microbiome of otitis media with effusion. Laryngoscope 126:2844–2851.
    68.
    Chan CL, Wabnitz D, Bassiouni A, Wormald P-J, Vreugde S, Psaltis AJ. 2017. Identification of the bacterial reservoirs for the middle ear using phylogenic analysis. JAMA Otolaryngol Head Neck Surg 143:155.
    69.
    Principi N, Marchisio P, Rosazza C, Sciarrabba CS, Esposito S. 2017. Acute otitis media with spontaneous tympanic membrane perforation. Eur J Clin Microbiol Infect Dis 36:11–18.
    70.
    Johnston J, Hoggard M, Biswas K, Astudillo‐García C, Radcliff FJ, Mahadevan M, Douglas RG. 2019. Pathogen reservoir hypothesis investigated by analyses of the adenotonsillar and middle ear microbiota. Int J Pediatr Otorhinolaryngol 118:103–109.
    71.
    Krueger A, Val S, Pérez-Losada M, Panchapakesan K, Devaney J, Duah V, DeMasson C, Poley M, Rose M, Preciado D. 2017. The relationship of the middle ear effusion microbiome to secretory mucin production in pediatric patients with chronic otitis media. Pediatr Infect Dis J 36:635–640.
    72.
    Neeff M, Biswas K, Hoggard M, Taylor MW, Douglas R. 2016. Molecular microbiological profile of chronic suppurative otitis media. J Clin Microbiol 54:2538–2546.
    73.
    Falkow S. 1988. Molecular Koch’s postulates applied to microbial pathogenicity. Clin Infect Dis 10(Suppl 2):S274–S276.
    74.
    Fredricks DN, Relman DA. 1996. Sequence-based identification of microbial pathogens: a reconsideration of Koch’s postulates. Clin Microbiol Rev 9:18–33.
    75.
    Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. 2014. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11:506–514.
    76.
    O’Toole PW, Marchesi JR, Hill C. 2017. Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nat Microbiol 2:17057.
    77.
    van der Poll T, Opal SM. 2009. Pathogenesis, treatment, and prevention of pneumococcal pneumonia. Lancet 374:1543–1556.
    78.
    Kadioglu A, Weiser JN, Paton JC, Andrew PW. 2008. The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease. Nat Rev Microbiol 6:288–301.
    79.
    de Vries SPW, Bootsma HJ, Hays JP, Hermans P. 2009. Molecular aspects of Moraxella catarrhalis pathogenesis. Microbiol Mol Biol Rev 73:389–406.
    80.
    Duell BL, Su YC, Riesbeck K. 2016. Host-pathogen interactions of nontypeable Haemophilus influenzae: from commensal to pathogen. FEBS Lett 590:3840–3853.
    81.
    Rose MC, Voynow JA. 2006. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev 86:245–278.
    82.
    Komatsu K, Jono H, Lim JH, Imasato A, Xu H, Kai H, Yan C, Li JD. 2008. Glucocorticoids inhibit nontypeable Haemophilus influenzae-induced MUC5AC mucin expression via MAPK phosphatase-1-dependent inhibition of p38 MAPK. Biochem Biophys Res Commun 377:763–768.
    83.
    Jedrzejas MJ. 2001. Pneumococcal virulence factors: structure and function. Microbiol Mol Biol Rev 65:187–207.
    84.
    Ziane H, Manageiro V, Ferreira E, Moura IB, Bektache S, Tazir M, Caniça M. 2016. Serotypes and antibiotic susceptibility of Streptococcus pneumoniae isolates from invasive pneumococcal disease and asymptomatic carriage in a pre-vaccination period, in Algeria. Front Microbiol 7:803.
    85.
    Ahrén IL, Janson H, Forsgren A, Riesbeck K. 2001. Protein D expression promotes the adherence and internalization of non-typeable Haemophilus influenzae into human monocytic cells. Microb Pathog 31:151–158.
    86.
    Val DS. 2015. Basic science concepts in otitis media pathophysiology and immunity: Role of mucins and inflammation, p 53–77. In Preciado D (ed), Otitis media: state of the art concepts and treatment. Springer, Cham, Switzerland.
    87.
    Murphy TF, Bakaletz LO, Smeesters PR. 2009. Microbial interactions in the respiratory tract. Pediatr Infect Dis J 28(10 Suppl):S121–S126.
    88.
    Van Eldere J, Slack MPE, Ladhani S, Cripps AW. 2014. Non-typeable Haemophilus influenzae, an under-recognised pathogen. Lancet Infect Dis 14:1281–1292.
    89.
    Lanie JA, Ng W-L, Kazmierczak KM, Andrzejewski TM, Davidsen TM, Wayne KJ, Tettelin H, Glass JI, Winkler ME. 2007. Genome sequence of Avery’s virulent serotype 2 strain D39 of Streptococcus pneumoniae and comparison with that of unencapsulated laboratory strain R6. J Bacteriol 189:38–51.
    90.
    Shen H, Yoshida H, Yan F, Li W, Xu F, Huang H, Jono H, Li JD. 2008. Synergistic induction of MUC5AC mucin by nontypeable Haemophilus influenzae and Streptococcus pneumoniae. Biochem Biophys Res Commun 365:795–800.
    91.
    Kerschner JE, Hong W, Khampang P, Johnston N. 2014. Differential response of gel-forming mucins to pathogenic middle ear bacteria. Int J Pediatr Otorhinolaryngol 78:1368–1373.
    92.
    Roy MG, Livraghi-Butrico A, Fletcher AA, McElwee MM, Evans SE, Boerner RM, Alexander SN, Bellinghausen LK, Song AS, Petrova YM, Tuvim MJ, Adachi R, Romo I, Bordt AS, Bowden MG, Sisson JH, Woodruff PG, Thornton DJ, Rousseau K, De la Garza MM, Moghaddam SJ, Karmouty-Quintana H, Blackburn MR, Drouin SM, Davis CW, Terrell KA, Grubb BR, O’Neal WK, Flores SC, Cota-Gomez A, Lozupone CA, Donnelly JM, Watson AM, Hennessy CE, Keith RC, Yang IV, Barthel L, Henson PM, Janssen WJ, Schwartz DA, Boucher RC, Dickey BF, Evans CM. 2014. Muc5b is required for airway defence. Nature 505:412–416.
    93.
    Johnson MK, Geoffroy C, Alouf JE. 1980. Binding of cholesterol by sulfhydryl-activated cytolysins. Infect Immun 27:97–101.
    94.
    Hirst RA, Kadioglu A, O’Callaghan C, Andrew PW. 2004. The role of pneumolysin in pneumococcal pneumonia and meningitis. Clin Exp Immunol 138:195–201.
    95.
    Marriott HM, Mitchell TJ, Dockrell DH. 2008. Pneumolysin: a double-edged sword during the host-pathogen interaction. Curr Mol Med 8:497–509.
    96.
    Feldman C, Anderson R, Cockeran R, Mitchell T, Cole P, Wilson R. 2002. The effects of pneumolysin and hydrogen peroxide, alone and in combination, on human ciliated epithelium in vitro. Respir Med 96:580–585.
    97.
    Post DMB, Ketterer MR, Coffin JE, Reinders LM, Munson RS, Bair T, Murphy TF, Foster ED, Gibson BW, Apicella MA. 2016. Comparative analyses of the lipooligosaccharides from nontypeable Haemophilus influenzae and Haemophilus haemolyticus show differences in sialic acid and phosphorylcholine modifications. Infect Immun 84:765–774.
    98.
    Figueira MA, Ram S, Goldstein R, Hood DW, Moxon ER, Pelton SI. 2007. Role of complement in defense of the middle ear revealed by restoring the virulence of nontypeable Haemophilus influenzae siaB mutants. Infect Immun 75:325–333.
    99.
    Johnston JW, Coussens NP, Allen S, Houtman JCD, Turner KH, Zaleski A, Ramaswamy S, Gibson BW, Apicella MA. 2008. Characterization of the N-acetyl-5-neuraminic acid-binding site of the extracytoplasmic solute receptor (SiaP) of nontypeable Haemophilus influenzae strain 2019. J Biol Chem 283:855–865.
    100.
    Jurcisek J, Greiner L, Watanabe H, Zaleski A, Apicella MA, Bakaletz LO. 2005. Role of sialic acid and complex carbohydrate biosynthesis in biofilm formation by nontypeable Haemophilus influenzae in the chinchilla middle ear. Infect Immun 73:3210–3218.
    101.
    Swords WE, Moore ML, Godzicki L, Bukofzer G, Mitten MJ, VonCannon J. 2004. Sialylation of lipooligosaccharides promotes biofilm formation by nontypeable Haemophilus influenzae. Infect Immun 72:106–113.
    102.
    Barocchi MA, Ries J, Zogaj X, Hemsley C, Albiger B, Kanth A, Dahlberg S, Fernebro J, Moschioni M, Masignani V, Hultenby K, Taddei AR, Beiter K, Wartha F, von Euler A, Covacci A, Holden DW, Normark S, Rappuoli R, Henriques-Normark B. 2006. A pneumococcal pilus influences virulence and host inflammatory responses. Proc Natl Acad Sci U S A 103:2857–2862.
    103.
    Danne C, Dramsi S. 2012. Pili of Gram-positive bacteria: roles in host colonization. Res Microbiol 163:645–658.
    104.
    Bagnoli F, Moschioni M, Donati C, Dimitrovska V, Ferlenghi I, Facciotti C, Muzzi A, Giusti F, Emolo C, Sinisi A, Hilleringmann M, Pansegrau W, Censini S, Rappuoli R, Covacci A, Masignani V, Barocchi MA. 2008. A second pilus type in Streptococcus pneumoniae is prevalent in emerging serotypes and mediates adhesion to host cells. J Bacteriol 190:5480–5492.
    105.
    Basset A, Herd M, Daly R, Dove SL, Malley R. 2017. The pneumococcal type 1 pilus genes are thermoregulated and are repressed by a member of the Snf2 protein family. J Bacteriol 199:e00078-17.
    106.
    Laurenceau R, Péhau-Arnaudet G, Baconnais S, Gault J, Malosse C, Dujeancourt A, Campo N, Chamot-Rooke J, Le Cam E, Claverys J-P, Fronzes R. 2013. A type IV pilus mediates DNA binding during natural transformation in Streptococcus pneumoniae. PLoS Pathog 9:e1003473.
    107.
    Muschiol S, Erlendsson S, Aschtgen M-S, Oliveira V, Schmieder P, de Lichtenberg C, Teilum K, Boesen T, Akbey U, Henriques-Normark B. 2017. Structure of the competence pilus major pilin ComGC in Streptococcus pneumoniae. J Biol Chem 292:14134–14146.
    108.
    Luke-Marshall NR, Sauberan SL, Campagnari AA. 2011. Comparative analyses of the Moraxella catarrhalis type-IV pilus structural subunit PilA. Gene 477:19–23.
    109.
    Carruthers MD, Tracy EN, Dickson AC, Ganser KB, Munson RS, Bakaletz LO. 2012. Biological roles of nontypeable Haemophilus influenzae type IV pilus proteins encoded by the pil and com operons. J Bacteriol 194:1927–1933.
    110.
    Novotny LA, Bakaletz LO. 2016. Intercellular adhesion molecule 1 serves as a primary cognate receptor for the type IV pilus of nontypeable Haemophilus influenzae. Cell Microbiol 18:1043–1055.
    111.
    Luke NR, Howlett AJ, Shao J, Campagnari AA. 2004. Expression of type IV pili by Moraxella catarrhalis is essential for natural competence and is affected by iron limitation. Infect Immun 72:6262–6270.
    112.
    Staunton DE, Merluzzi VJ, Rothlein R, Barton R, Marlin SD, Springer TA. 1989. A cell adhesion molecule, ICAM-1, is the major surface receptor for rhinoviruses. Cell 56:849–853.
    113.
    Fink DL, Buscher AZ, Green B, Fernsten P, St Geme JW, III. 2003. The Haemophilus influenzae Hap autotransporter mediates microcolony formation and adherence to epithelial cells and extracellular matrix via binding regions in the C-terminal end of the passenger domain. Cell Microbiol 5:175–186.
    114.
    Ahrén IL, Williams DL, Rice PJ, Forsgren A, Riesbeck K. 2001. The importance of a β-glucan receptor in the nonopsonic entry of nontypeable Haemophilus influenzae into human monocytic and epithelial cells. J Infect Dis 184:150–158.
    115.
    Cundell DR, Gerard NP, Gerard C, Idanpaan-Heikkila I, Tuomanen EI. 1995. Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 377:435–438.
    116.
    Young NM, Foote SJ, Wakarchuk WW. 2013. Review of phosphocholine substituents on bacterial pathogen glycans: synthesis, structures and interactions with host proteins. Mol Immunol 56:563–573.
    117.
    Johnson RW, McGillivary G, Denoël P, Poolman J, Bakaletz LO. 2011. Abrogation of nontypeable Haemophilus influenzae protein D function reduces phosphorylcholine decoration, adherence to airway epithelial cells, and fitness in a chinchilla model of otitis media. Vaccine 29:1211–1221.
    118.
    Clark SE, Weiser JN. 2013. Microbial modulation of host immunity with the small molecule phosphorylcholine. Infect Immun 81:392–401.
    119.
    Pang B, Winn D, Johnson R, Hong W, West-Barnette S, Kock N, Swords WE. 2008. Lipooligosaccharides containing phosphorylcholine delay pulmonary clearance of nontypeable Haemophilus influenzae. Infect Immun 76:2037–2043.
    120.
    Nelson AL, Ries J, Bagnoli F, Dahlberg S, Fälker S, Rounioja S, Tschöp J, Morfeldt E, Ferlenghi I, Hilleringmann M, Holden DW, Rappuoli R, Normark S, Barocchi MA, Henriques-Normark B. 2007. RrgA is a pilus-associated adhesin in Streptococcus pneumoniae. Mol Microbiol 66:329–340.
    121.
    Rosch JW, Mann B, Thornton J, Sublett J, Tuomanen E. 2008. Convergence of regulatory networks on the pilus locus of Streptococcus pneumoniae. Infect Immun 76:3187–3196.
    122.
    Hallström T, Singh B, Resman F, Blom AM, Mörgelin M, Riesbeck K. 2011. Haemophilus influenzae protein E binds to the extracellular matrix by concurrently interacting with laminin and vitronectin. J Infect Dis 204:1065–1074.
    123.
    Singh B, Al-Jubair T, Mörgelin M, Thunnissen MM, Riesbeck K. 2013. The unique structure of haemophilus influenzae protein E reveals multiple binding sites for host factors. Infect Immun 81:801–814.
    124.
    Su YC, Mukherjee O, Singh B, Hallgren O, Westergren-Thorsson G, Hood D, Riesbeck K. 2016. Haemophilus influenzae p4 interacts with extracellular matrix proteins promoting adhesion and serum resistance. J Infect Dis 213:314–323.
    125.
    Voges M, Bachmann V, Kammerer R, Gophna U, Hauck CR. 2010. CEACAM1 recognition by bacterial pathogens is species-specific. BMC Microbiol 10:117.
    126.
    Hill DJ, Toleman MA, Evans DJ, Villullas S, Van Alphen L, Virji M. 2001. The variable P5 proteins of typeable and non-typeable Haemophilus influenzae target human CEACAM1. Mol Microbiol 39:850–862.
    127.
    Skotnicka B, Hassmann E. 2008. Proinflammatory and immunoregulatory cytokines in the middle ear effusions. Int J Pediatr Otorhinolaryngol 72:13–17.
    128.
    Kerschner JE, Meyer TK, Burrows A. 2004. Chinchilla middle ear epithelial mucin gene expression in response to inflammatory cytokines. Arch Otolaryngol Head Neck Surg 130:1163–1167.
    129.
    Leibovitz E, Dagan R, Laver JH, Piglansky L, Raiz S, Abboud MR, Fliss DM, Leiberman A, Barzilai A. 2000. Interleukin 8 in middle ear fluid during acute otitis media: correlation with aetiology and bacterial eradication. Arch Dis Child 82:165–168.
    130.
    Si Y, Zhang ZG, Chen SJ, Zheng YQ, Chen YB, Liu Y, Jiang H, Feng LQ, Huang X. 2014. Attenuated TLRs in middle ear mucosa contributes to susceptibility of chronic suppurative otitis media. Hum Immunol 75:771–776.
    131.
    Zielnik-Jurkiewicz B, Stankiewicz-Szymczak W. 2016. Pro-inflammatory interleukins in middle ear effusions from atopic and non-atopic children with chronic otitis media with effusion. Eur Arch Otorhinolaryngol 273:1369–1378.
    132.
    Lee HY, Chung JH, Lee SK, Byun JY, Kim YI, Yeo SG. 2013. Toll-like receptors, cytokines & nitric oxide synthase in patients with otitis media with effusion. Indian J Med Res 138:523–530.
    133.
    Slevogt H, Zabel S, Opitz B, Hocke A, Eitel J, N’guessan PD, Lucka L, Riesbeck K, Zimmermann W, Zweigner J, Temmesfeld-Wollbrueck B, Suttorp N, Singer BB. 2008. CEACAM1 inhibits Toll-like receptor 2-triggered antibacterial responses of human pulmonary epithelial cells. Nat Immunol 9:1270–1278.
    134.
    Weidenmaier C, Peschel A. 2008. Teichoic acids and related cell-wall glycopolymers in Gram-positive physiology and host interactions. Nat Rev Microbiol 6:276–287.
    135.
    Gisch N, Kohler T, Ulmer AJ, Müthing J, Pribyl T, Fischer K, Lindner B, Hammerschmidt S, Zähringer U. 2013. Structural reevaluation of Streptococcus pneumoniae lipoteichoic acid and new insights into its immunostimulatory potency. J Biol Chem 288:15654–15667.
    136.
    Zhang Q, Bagrade L, Bernatoniene J, Clarke E, Paton JC, Mitchell TJ, Nunez DA, Finn A. 2007. Low CD4 T cell immunity to pneumolysin is associated with nasopharyngeal carriage of pneumococci in children. J Infect Dis 195:1194–1202.
    137.
    Rabes A, Suttorp N, Opitz B. 2016. Inflammasomes in pneumococcal infection: innate immune sensing and bacterial evasion strategies. Curr Top Microbiol Immunol 397:215–227.
    138.
    Jalalvand F, Su YC, Mörgelin M, Brant M, Hallgren O, Westergren-Thorsson G, Singh B, Riesbeck K. 2013. Haemophilus influenzae protein F mediates binding to laminin and human pulmonary epithelial cells. J Infect Dis 207:803–813.
    139.
    Forsgren A, Brant M, Möllenkvist A, Muyombwe A, Janson H, Woin N, Riesbeck K. 2001. Isolation and characterization of a novel IgD-binding protein from Moraxella catarrhalis. J Immunol 167:2112–2120.
    140.
    Clark SE, Snow J, Li J, Zola TA, Weiser JN. 2012. Phosphorylcholine allows for evasion of bactericidal antibody by Haemophilus influenzae. PLoS Pathog 8:e1002521.
    141.
    Lysenko ES, Gould J, Bals R, Wilson JM, Weiser JN. 2000. Bacterial phosphorylcholine decreases susceptibility to the antimicrobial peptide LL-37/hCAP18 expressed in the upper respiratory tract. Infect Immun 68:1664–1671.
    142.
    Jurcisek JA, Bakaletz LO. 2007. Biofilms formed by nontypeable Haemophilus influenzae in vivo contain both double-stranded DNA and type IV pilin protein. J Bacteriol 189:3868–3875.
    143.
    Webster P, Wu S, Gomez G, Apicella M, Plaut AG, St Geme JW, III. 2006. Distribution of bacterial proteins in biofilms formed by Non-typeable Haemophilus influenzae. J Histochem Cytochem 54:829–842.
    144.
    West-Barnette S, Rockel A, Swords WE. 2006. Biofilm growth increases phosphorylcholine content and decreases potency of nontypeable Haemophilus influenzae endotoxins. Infect Immun 74:1828–1836.
    145.
    Jones EA, McGillivary G, Bakaletz LO. 2013. Extracellular DNA within a nontypeable haemophilus influenzae-induced biofilm binds human beta defensin-3 and reduces its antimicrobial activity. J Innate Immun 5:24–38.
    146.
    Rosenow C, Ryan P, Weiser JN, Johnson S, Fontan P, Ortqvist A, Masure HR. 1997. Contribution of novel choline-binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae. Mol Microbiol 25:819–829.
    147.
    Clark SE, Eichelberger KR, Weiser JN. 2013. Evasion of killing by human antibody and complement through multiple variations in the surface oligosaccharide of Haemophilus influenzae. Mol Microbiol 88:603–618.
    148.
    Michel LV, Snyder J, Schmidt R, Milillo J, Grimaldi K, Kalmeta B, Khan MN, Sharma S, Wright LK, Pichichero ME. 2013. Dual orientation of the outer membrane lipoprotein P6 of nontypeable Haemophilus influenzae. J Bacteriol 195:3252–3259.
    149.
    Iannelli F, Chiavolini D, Ricci S, Oggioni MR, Pozzi G. 2004. Pneumococcal surface protein C contributes to sepsis caused by Streptococcus pneumoniae in mice. Infect Immun 72:3077–3080.
    150.
    Quin LR, Carmicle S, Dave S, Pangburn MK, Evenhuis JP, McDaniel LS. 2005. In vivo binding of complement regulator factor H by Streptococcus pneumoniae. J Infect Dis 192:1996–2003.
    151.
    Nordström T, Blom AM, Forsgren A, Riesbeck K. 2004. The emerging pathogen Moraxella catarrhalis interacts with complement inhibitor C4b binding protein through ubiquitous surface proteins A1 and A2. J Immunol 173:4598–4606.
    152.
    Nordstrom T, Blom AM, Tan TT, Forsgren A, Riesbeck K. 2005. Ionic binding of C3 to the human pathogen Moraxella catarrhalis is a unique mechanism for combating innate immunity. J Immunol 175:3628–3636.
    153.
    Attia AS, Ram S, Rice PA, Hansen EJ. 2006. Binding of vitronectin by the Moraxella catarrhalis UspA2 protein interferes with late stages of the complement cascade. Infect Immun 74:1597–1611.
    154.
    Rosadini CV, Ram S, Akerley BJ. 2014. Outer membrane protein p5 is required for resistance of nontypeable haemophilus influenzae to both the classical and alternative complement pathways. Infect Immun 82:640–649.
    155.
    Hall-Stoodley L, Hu FZ, Gieseke A, Nistico L, Nguyen D, Hayes J, Forbes M, Greenberg DP, Dice B, Burrows A, Wackym PA, Stoodley P, Post JC, Ehrlich GD, Kerschner JE. 2006. Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media. JAMA 296:202.
    156.
    Pang B, Swords WE. 2017. Haemophilus parainfluenzae strain ATCC 33392 forms biofilms in vitro and during experimental otitis media infections. Infect Immun 85:e01070-16.
    157.
    Gu X, Keyoumu Y, Long L, Zhang H. 2014. Detection of bacterial biofilms in different types of chronic otitis media. Eur Arch Otorhinolaryngol 271:2877–2883.
    158.
    Rayner MG, Zhang Y, Gorry MC, Chen Y, Post JC, Ehrlich GD. 1998. Evidence of bacterial metabolic activity in culture-negative otitis media with effusion. JAMA 279:296.
    159.
    Post JC. 2001. Direct evidence of bacterial biofilms in otitis media. Laryngoscope 111:2083–2094.
    160.
    Ehrlich GD, Veeh R, Wang X, Costerton JW, Hayes JD, Hu FZ, Daigle BJ, Ehrlich MD, Post JC. 2002. Mucosal biofilm formation on middle-ear mucosa in the chinchilla model of otitis media. JAMA 287:1710–1715.
    161.
    Wolcott RD, Ehrlich GD. 2008. Biofilms and chronic infections. JAMA 299:2682.
    162.
    Schachern PA, Tsuprun V, Cureoglu S, Ferrieri P, Briles DE, Paparella MM, Juhn S. 2009. Virulence of pneumococcal proteins on the inner ear. Arch Otolaryngol Head Neck Surg 135:657–661.
    163.
    Idicula WK, Jurcisek JA, Cass ND, Ali S, Goodman SD, Elmaraghy CA, Jatana KR, Bakaletz LO. 2016. Identification of biofilms in post-tympanostomy tube otorrhea. Laryngoscope 126:1946–1951.
    164.
    Novotny L, Brockman K, Mokrzan E, Jurcisek J, Bakaletz L. 2019. Biofilm biology and vaccine strategies for otitis media due to nontypeable Haemophilus influenzae. J Pediatr Infect Dis 14:69–77.
    165.
    Broides A, Dagan R, Greenberg D, Givon‐Lavi N, Leibovitz E. 2009. Acute otitis media caused by Moraxella catarrhalis: epidemiologic and clinical characteristics. Clin Infect Dis 49:1641–1647.
    166.
    Perez AC, Pang B, King LB, Tan L, Murrah KA, Reimche JL, Wren JT, Richardson SH, Ghandi U, Swords WE. 2014. Residence of Streptococcus pneumoniae and Moraxella catarrhalis within polymicrobial biofilm promotes antibiotic resistance and bacterial persistence in vivo. Pathog Dis 70:280–288.
    167.
    Weimer KED, Juneau RA, Murrah KA, Pang B, Armbruster CE, Richardson SH, Swords WE. 2011. Divergent mechanisms for passive pneumococcal resistance to β-lactam antibiotics in the presence of Haemophilus influenzae. J Infect Dis 203:549–555.
    168.
    Cope EK, Goldstein-Daruech N, Kofonow JM, Christensen L, McDermott B, Monroy F, Palmer JN, Chiu AG, Shirtliff ME, Cohen NA, Leid JG. 2011. Regulation of virulence gene expression resulting from Streptococcus pneumoniae and nontypeable Haemophilus influenzae interactions in chronic disease. PLoS One 6:e28523.
    169.
    Kumpu M, Swanljung E, Tynkkynen S, Hatakka K, Kekkonen RA, Järvenpää S, Korpela R, Pitkäranta A. 2013. Recovery of probiotic Lactobacillus rhamnosus GG in tonsil tissue after oral administration: randomised, placebo-controlled, double-blind clinical trial. Br J Nutr 109:2240–2246.
    170.
    Swanljung E, Tapiovaara L, Lehtoranta L, Mäkivuokko H, Roivainen M, Korpela R, Pitkäranta A. 2015. Lactobacillus rhamnosus GG in adenoid tissue: double-blind, placebo-controlled, randomized clinical trial. Acta Otolaryngol 135:824–830.
    171.
    Tapiovaara L, Lehtoranta L, Swanljung E, Mäkivuokko H, Laakso S, Roivainen M, Korpela R, Pitkäranta A. 2014. Lactobacillus rhamnosus GG in the middle ear after randomized, double-blind, placebo-controlled oral administration. Int J Pediatr Otorhinolaryngol 78:1637–1641.
    172.
    Broeckx G, Vandenheuvel D, Claes IJJ, Lebeer S, Kiekens F. 2016. Drying techniques of probiotic bacteria as an important step towards the development of novel pharmabiotics. Int J Pharm 505:303–318.
    173.
    Segers ME, Lebeer S. 2014. Towards a better understanding of Lactobacillus rhamnosus GG-host interactions. Microb Cell Fact 13:S7.
    174.
    Niittynen L, Pitkäranta A, Korpela R. 2012. Probiotics and otitis media in children. Int J Pediatr Otorhinolaryngol 76:465–470.
    175.
    Marom T, Marchisio P, Tamir SO, Torretta S, Gavriel H, Esposito S. 2016. Complementary and alternative medicine treatment options for otitis media. Medicine (Baltimore) 95:e2695.
    176.
    Roos K, Hakansson EG, Holm S. 2001. Effect of recolonisation with “interfering” alpha streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial. BMJ 322:210–212.
    177.
    Tano K, Grahn Håkansson E, Holm SE, Hellström S. 2002. A nasal spray with alpha-haemolytic streptococci as long term prophylaxis against recurrent otitis media. Int J Pediatr Otorhinolaryngol 62:17–23.
    178.
    Santagati M, Scillato M, Muscaridola N, Metoldo V, La Mantia I, Stefani S. 2015. Colonization, safety, and tolerability study of the Streptococcus salivarius 24SMBc nasal spray for its application in upper respiratory tract infections. Eur J Clin Microbiol Infect Dis 34:2075–2080.
    179.
    La Mantia I, Varricchio A, Ciprandi G. 2017. Bacteriotherapy with Streptococcus salivarius 24SMB and Streptococcus oralis 89a nasal spray for preventing recurrent acute otitis media in children: a real-life clinical experience. Int J Gen Med 10:171–175.
    180.
    Skovbjerg S, Roos K, Holm SE, Grahn Hakansson E, Nowrouzian F, Ivarsson M, Adlerberth I, Wold AE. 2009. Spray bacteriotherapy decreases middle ear fluid in children with secretory otitis media. Arch Dis Child 94:92–98.
    181.
    Marchisio P, Santagati M, Scillato M, Baggi E, Fattizzo M, Rosazza C, Stefani S, Esposito S, Principi N. 2015. Streptococcus salivarius 24SMB administered by nasal spray for the prevention of acute otitis media in otitis-prone children. Eur J Clin Microbiol Infect Dis 34:2377–2383.
    182.
    Mårtensson A, Greiff L, Lamei SS, Lindstedt M, Olofsson TC, Vasquez A, Cervin A. 2016. Effects of a honeybee lactic acid bacterial microbiome on human nasal symptoms, commensals, and biomarkers. Int Forum Allergy Rhinol 6:956–963.
    183.
    Mandal MD, Mandal S. 2011. Honey: its medicinal property and antibacterial activity. Asian Pac J Trop Biomed 1:154–160.
    184.
    Claes IJ, Vargas García CE, Lebeer S. 2015. Novel opportunities for the exploitation of host–microbiome interactions in the intestine. Curr Opin Biotechnol 32:28–34.
    185.
    Lebeer S, Vanderleyden J, De Keersmaecker S. 2008. Genes and molecules of lactobacilli supporting probiotic action. Microbiol Mol Biol Rev 72:728–764.
    186.
    Deborah S, Prathibha KM. 2014. Measurement of nasal mucociliary clearance. Clin Res Pulmonol 2:1019.
    187.
    Kankainen M, Paulin L, Tynkkynen S, von Ossowski I, Reunanen J, Partanen P, Satokari R, Vesterlund S, Hendrickx APA, Lebeer S, De Keersmaecker SCJ, Vanderleyden J, Hamalainen T, Laukkanen S, Salovuori N, Ritari J, Alatalo E, Korpela R, Mattila-Sandholm T, Lassig A, Hatakka K, Kinnunen KT, Karjalainen H, Saxelin M, Laakso K, Surakka A, Palva A, Salusjarvi T, Auvinen P, de Vos WM. 2009. Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human-mucus binding protein. Proc Natl Acad Sci 106:17193–17198.
    188.
    Call EK, Klaenhammer TR. 2013. Relevance and application of sortase and sortase-dependent proteins in lactic acid bacteria. Front Microbiol 4:73.
    189.
    Wuyts S, Wittouck S, De Boeck I, Allonsius CN, Pasolli E, Segata N, Lebeer S. 2017. Large-scale phylogenomics of the Lactobacillus casei group highlights taxonomic inconsistencies and reveals novel clade-associated features. mSystems 2:e00061-17.
    190.
    Petrova MI, Lievens E, Verhoeven TLA, Macklaim JM, Gloor G, Schols D, Vanderleyden J, Reid G, Lebeer S. 2016. The lectin-like protein 1 in Lactobacillus rhamnosus GR-1 mediates tissue-specific adherence to vaginal epithelium and inhibits urogenital pathogens. Sci Rep 6:37437.
    191.
    Burgain J, Scher J, Lebeer S, Vanderleyden J, Corgneau M, Guerin J, Caillet C, Duval JFL, Francius G, Gaiani C. 2015. Impacts of pH-mediated EPS structure on probiotic bacterial pili-whey proteins interactions. Colloids Surfaces B Biointerfaces 134:332–338.
    192.
    De Rudder C, Calatayud Arroyo M, Lebeer S, Van de Wiele T. 2018. Modelling upper respiratory tract diseases: getting grips on host-microbe interactions in chronic rhinosinusitis using in vitro technologies. Microbiome 6:75.
    193.
    Lafontaine ER, Wall D, Vanlerberg SL, Donabedian H, Sledjeski DD. 2004. Moraxella catarrhalis coaggregates with Streptococcus pyogenes and modulates interactions of S. pyogenes with human epithelial cells. Infect Immun 72:6689–6693.
    194.
    Allonsius CN, van den Broek MFL, De Boeck I, Kiekens S, Oerlemans EFM, Kiekens F, Foubert K, Vandenheuvel D, Cos P, Delputte P, Lebeer S. 2017. Interplay between Lactobacillus rhamnosus GG and Candida and the involvement of exopolysaccharides. Microb Biotechnol 10:1753–1763.
    195.
    Guglielmetti S, Taverniti V, Minuzzo M, Arioli S, Zanoni I, Stuknyte M, Granucci F, Karp M, Mora D. 2010. A dairy bacterium displays in vitro probiotic properties for the pharyngeal mucosa by antagonizing group A streptococci and modulating the immune response. Infect Immun 78:4734–4743.
    196.
    Wong S-S, Quan Toh Z, Dunne EM, Mulholland EK, Tang MLK, Robins-Browne RM, Licciardi PV, Satzke C. 2013. Inhibition of Streptococcus pneumoniae adherence to human epithelial cells in vitro by the probiotic Lactobacillus rhamnosus GG. BMC Res Notes 6:135.
    197.
    van den Broek MFL, De Boeck I, Claes IJJ, Nizet V, Lebeer S. 2018. Multifactorial inhibition of lactobacilli against the respiratory tract pathogen Moraxella catarrhalis. Benef Microbes 9:429–439.
    198.
    Siegel SJ, Weiser JN. 2015. Mechanisms of bacterial colonization of the respiratory tract. Annu Rev Microbiol 69:425–444.
    199.
    Underwood M, Bakaletz L. 2011. Innate immunity and the role of defensins in otitis media. Curr Allergy Asthma Rep 11:499–507.
    200.
    Alakomi H, Skyttä E, Saarela M, Mattila-Sandholm T, Latva-Kala K, Helander IM. 2000. Lactic acid permeabilizes gram-negative bacteria by disrupting the outer membrane. Appl Environ Microbiol 66:2001–2005.
    201.
    De Keersmaecker SCJ, Verhoeven TLA, Desair J, Marchal K, Vanderleyden J, Nagy I. 2006. Strong antimicrobial activity of Lactobacillus rhamnosus GG against Salmonella typhimurium is due to accumulation of lactic acid. FEMS Microbiol Lett 259:89–96.
    202.
    Makras L, Triantafyllou V, Fayol-Messaoudi D, Adriany T, Zoumpopoulou G, Tsakalidou E, Servin A, De Vuyst L. 2006. Kinetic analysis of the antibacterial activity of probiotic lactobacilli towards Salmonella enterica serovar Typhimurium reveals a role for lactic acid and other inhibitory compounds. Res Microbiol 157:241–247.
    203.
    Makras L, De Vuyst L. 2006. The in vitro inhibition of Gram-negative pathogenic bacteria by bifidobacteria is caused by the production of organic acids. Int Dairy J 16:1049–1057.
    204.
    Hütt P, Shchepetova J, Lõivukene K, Kullisaar T, Mikelsaar M. 2006. Antagonistic activity of probiotic lactobacilli and bifidobacteria against entero- and uropathogens. J Appl Microbiol 100:1324–1332.
    205.
    Marianelli C, Cifani N, Pasquali P. 2010. Evaluation of antimicrobial activity of probiotic bacteria against Salmonella enterica subsp. enterica serovar typhimurium 1344 in a common medium under different environmental conditions. Res Microbiol 161:673–680.
    206.
    Barefoot SF, Klaenhammer TR. 1983. Detection and activity of lactacin B, a bacteriocin produced by Lactobacillus acidophilus. Appl Environ Microbiol 45:1808–1815.
    207.
    Muriana PM, Klaenhammer TR. 1991. Purification and partial characterization of lactacin F, a bacteriocin produced by Lactobacillus acidophilus 11088. Appl Environ Microbiol 57:114–121.
    208.
    Tabasco R, García-Cayuela T, Peláez C, Requena T. 2009. Lactobacillus acidophilus La-5 increases lactacin B production when it senses live target bacteria. Int J Food Microbiol 132:109–116.
    209.
    Gonzalez B, Arca P, Mayo B, Suarez JE. 1994. Detection, purification, and partial characterization of plantaricin C, a bacteriocin produced by a Lactobacillus plantarum strain of dairy origin. Appl Environ Microbiol 60:2158–2163.
    210.
    Zacharof MP, Lovitt RW. 2012. Bacteriocins produced by lactic acid bacteria a review article. APCBEE Procedia 2:50–56.
    211.
    Lu R, Fasano S, Madayiputhiya N, Morin NP, Nataro J, Fasano A. 2009. Isolation, identification, and characterization of small bioactive peptides from Lactobacillus GG conditional media that exert both anti-Gram-negative and Gram-positive bactericidal activity. J Pediatr Gastroenterol Nutr 49:23–30.
    212.
    Goldstein BP, Wei J, Greenberg K, Novick R. 1998. Activity of nisin against Streptococcus pneumoniae, in vitro, and in a mouse infection model. J Antimicrob Chemother 42:277–278.
    213.
    Petrova MI, Imholz NCE, Verhoeven TLA, Balzarini J, Van Damme EJM, Schols D, Vanderleyden J, Lebeer S. 2016. Lectin-like molecules of Lactobacillus rhamnosus GG inhibit pathogenic Escherichia coli and Salmonella biofilm formation. PLoS One 11:e0161337.
    214.
    Schwandt LQ, Van Weissenbruch R, Stokroos I, Van Der Mei HC, Busscher HJ, Albers F. 2004. Prevention of biofilm formation by dairy products and N-acetylcysteine on voice prostheses in an artificial throat. Acta Otolaryngol 124:726–731.
    215.
    Pericone CD, Overweg K, Hermans PWM, Weiser JN. 2000. Inhibitory and bactericidal effects of hydrogen peroxide production by Streptococcus pneumoniae on other inhabitants of the upper respiratory tract. Infect Immun 68:3990–3997.
    216.
    Servin AL. 2004. Antagonistic activities of Lactobacilli and Bifidobacteria against microbial pathogens. FEMS Microbiol Rev 28:405–440.
    217.
    Petrova MI, Lievens E, Malik S, Imholz N, Lebeer S. 2015. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Front Physiol 6:81.
    218.
    de Kievit TR, Iglewski BH. 2000. Bacterial quorum sensing in pathogenic relationships. Infect Immun 68:4839–4849.
    219.
    Lebeer S, De Keersmaecker SCJ, Verhoeven TLA, Fadda AA, Marchal K, Vanderleyden J. 2007. Functional analysis of luxS in the probiotic strain Lactobacillus rhamnosus GG reveals a central metabolic role important for growth and biofilm formation. J Bacteriol 189:860–871.
    220.
    Vidal JE, Ludewick HP, Kunkel RM, Zähner D, Klugman KP. 2011. The luxS-dependent quorum-sensing system regulates early biofilm formation by Streptococcus pneumoniae strain D39. Infect Immun 79:4050–4060.
    221.
    Armbruster CE, Hong W, Pang B, Dew KE, Juneau RA, Byrd MS, Love CF, Kock ND, Swords WE. 2009. LuxS promotes biofilm maturation and persistence of nontypeable Haemophilus influenzae in vivo via modulation of lipooligosaccharides on the bacterial surface. Infect Immun 77:4081–4091.
    222.
    Joyce EA, Kawale A, Censini S, Kim CC, Covacci A, Falkow S. 2004. LuxS is required for persistent pneumococcal carriage and expression of virulence and biosynthesis genes. Infect Immun 72:2964–2975.
    223.
    Stroeher UH, Paton AW, Ogunniyi AD, Paton JC. 2003. Mutation of luxS of Streptococcus pneumoniae affects virulence in a mouse model. Infect Immun 71:3206–3212.
    224.
    Daines DA, Bothwell M, Furrer J, Unrath W, Nelson K, Jarisch J, Melrose N, Greiner L, Apicella M, Smith AL. 2005. Haemophilus influenzae luxS mutants form a biofilm and have increased virulence. Microb Pathog 39:87–96.
    225.
    Armbruster CE, Hong W, Pang B, Weimer KED, Juneau RA, Turner J, Swords WE. 2010. Indirect pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in polymicrobial otitis media occurs via interspecies quorum signaling. mBio 1:e00102-10.
    226.
    Vendeville A, Winzer K, Heurlier K, Tang CM, Hardie KR. 2005. Making “sense” of metabolism: autoinducer-2, LUXS and pathogenic bacteria. Nat Rev Microbiol 3:383–396.
    227.
    Bron PA, Kleerebezem M, Brummer R-J, Cani PD, Mercenier A, MacDonald TT, Garcia-Ródenas CL, Wells JM. 2017. Can probiotics modulate human disease by impacting intestinal barrier function? Br J Nutr 117:93–107.
    228.
    Yeo N-K, Jang YJ. 2010. Rhinovirus infection-induced alteration of tight junction and adherens junction components in human nasal epithelial cells. Laryngoscope 120:346–352.
    229.
    Martens K, Pugin B, De Boeck I, Spacova I, Steelant B, Seys SF, Lebeer S, Hellings PW. 2018. Probiotics for the airways: potential to improve epithelial and immune homeostasis. Allergy 73:1954–1963.
    230.
    Karczewski J, Troost FJ, Konings I, Dekker J, Kleerebezem M, Brummer RJM, Wells JM. 2010. Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. Am J Physiol Gastrointest Liver Physiol 298:G851–G859.
    231.
    Seth A, Yan F, Polk DB, Rao RK. 2008. Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism. Am J Physiol Gastrointest Liver Physiol 294:G1060–G1069.
    232.
    Yan F, Cao H, Cover TL, Whitehead R, Washington MK, Polk DB. 2007. Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology 132:562–575.
    233.
    Yan F, Cao H, Cover TL, Washington MK, Shi Y, Liu L, Chaturvedi R, Peek RM, Wilson KT, Polk DB. 2011. Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism. J Clin Invest 121:2242–2253.
    234.
    Steelant B, Seys SF, Boeckxstaens G, Akdis CA, Ceuppens JL, Hellings PW. 2016. Restoring airway epithelial barrier dysfunction: a new therapeutic challenge in allergic airway disease. Rhinology 54:195–205.
    235.
    Lee Y-S, Kim T-Y, Kim Y, Lee S-H, Kim S, Kang SW, Yang J-Y, Baek I-J, Sung YH, Park Y-Y, Hwang SW, O E, Kim KS, Liu S, Kamada N, Gao N, Kweon M-N. 2018. Microbiota-derived lactate accelerates intestinal stem-cell-mediated epithelial development. Cell Host Microbe 24:833–846.e6.
    236.
    Madsen KL. 2012. Enhancement of epithelial barrier function by probiotics. J Epithel Biol Pharmacol 5:55–59.
    237.
    Lehrer RI, Jung G, Ruchala P, Wang W, Micewicz ED, Waring AJ, Gillespie EJ, Bradley KA, Ratner AJ, Rest RF, Lu W. 2009. Human β-defensins inhibit hemolysis mediated by cholesterol-dependent cytolysins. Infect Immun 77:4028–4040.
    238.
    Wehkamp J, Harder J, Weichenthal M, Schwab M, Schäffeler E, Schlee M, Herrlinger KR, Stallmach A, Noack F, Fritz P, Schröder JM, Bevins CL, Fellermann K, Stange EF. 2004. NOD2 (CARD15) mutations in Crohn’s disease are associated with diminished mucosal β-defensin expression. Gut 53:1658–1664.
    239.
    Delcour J, Ferain T, Deghorain M, Palumbo E, Hols P. 1999. The biosynthesis and functionality of the cell-wall of lactic acid bacteria. Antonie van Leeuwenhoek 76:159–184.
    240.
    Macho Fernandez E, Fernandez EM, Valenti V, Rockel C, Hermann C, Pot B, Boneca IG, Grangette C. 2011. Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide. Gut 60:1050–1059.
    241.
    Maxson S, Yamauchi T. 1996. Acute otitis media. Pediatr Rev 17:191–195.
    242.
    Schlee M, Harder J, Köten B, Stange EF, Wehkamp J, Fellermann K. 2008. Probiotic lactobacilli and VSL#3 induce enterocyte β-defensin 2. Clin Exp Immunol 151:528–535.
    243.
    Bishop-Hurley SL, Schmidt FJ, Erwin AL, Smith AL. 2005. Peptides selected for binding to a virulent strain of Haemophilus influenzae by phage display are bactericidal. Antimicrob Agents Chemother 49:2972–2978.
    244.
    Lee H-Y, Andalibi A, Webster P, Moon S-K, Teufert K, Kang S-H, Li J-D, Nagura M, Ganz T, Lim DJ. 2004. Antimicrobial activity of innate immune molecules against Streptococcus pneumoniae, Moraxella catarrhalis and nontypeable Haemophilus influenzae. BMC Infect Dis 4:12.
    245.
    McGillivary G, Ray WC, Bevins CL, Munson RS, Bakaletz LO. 2007. A member of the cathelicidin family of antimicrobial peptides is produced in the upper airway of the chinchilla and its mRNA expression is altered by common viral and bacterial co-pathogens of otitis media. Mol Immunol 44:2446–2458.
    246.
    Bu H-F, Wang X, Zhu Y-Q, Williams RY, Hsueh W, Zheng X, Rozenfeld RA, Zuo X-L, Tan X-D. 2006. Lysozyme-modified probiotic components protect rats against polymicrobial sepsis: role of macrophages and cathelicidin-related innate immunity. J Immunol 177:8767–8776.
    247.
    Lebeer S, Vanderleyden J, De Keersmaecker S. 2010. Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens. Nat Rev Microbiol 8:171–184.
    248.
    Konstantinov SR, Smidt H, de Vos WM, Bruijns SCM, Singh SK, Valence F, Molle D, Lortal S, Altermann E, Klaenhammer TR, van Kooyk Y. 2008. S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proc Natl Acad Sci U S A 105:19474–19479.
    249.
    Borchers AT, Selmi C, Meyers FJ, Keen CL, Gershwin ME. 2009. Probiotics and immunity. J Gastroenterol 44:26–46.
    250.
    Feleszko W, Jaworska J, Rha RD, Steinhausen S, Avagyan A, Jaudszus A, Ahrens B, Groneberg DA, Wahn U, Hamelmann E. 2007. Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma. Clin Exp Allergy 37:498–505.
    251.
    Spacova I, Petrova MI, Fremau A, Pollaris L, Vanoirbeek J, Ceuppens JL, Seys S, Lebeer S. 2019. Intranasal administration of probiotic Lactobacillus rhamnosus GG prevents birch pollen-induced allergic asthma in a murine model. Allergy 74:100–1.
    252.
    Toh ZQ, Anzela A, Tang MLK, Licciardi PV. 2012. Probiotic therapy as a novel approach for allergic disease. Front Pharmacol 3:171.
    253.
    Harata G, He F, Hiruta N, Kawase M, Kubota A, Hiramatsu M, Yausi H. 2010. Intranasal administration of Lactobacillus rhamnosus GG protects mice from H1N1 influenza virus infection by regulating respiratory immune responses. Lett Appl Microbiol 50:597–602.
    254.
    Lebeer S, Claes I, Tytgat HLP, Verhoeven TLA, Marien E, von Ossowski I, Reunanen J, Palva A, de Vos WM, De Keersmaecker SCJ, Vanderleyden J. 2012. Functional analysis of lactobacillus rhamnosus GG pili in relation to adhesion and immunomodulatory interactions with intestinal epithelial cells. Appl Environ Microbiol 78:185–193.
    255.
    Vargas García CE, Petrova M, Claes IJJ, De Boeck I, Verhoeven TLA, Dilissen E, von Ossowski I, Palva A, Bullens DM, Vanderleyden J, Lebeer S. 2015. Piliation of Lactobacillus rhamnosus GG promotes adhesion, phagocytosis, and cytokine modulation in macrophages. Appl Environ Microbiol 81:2050–2062.
    256.
    Petrova MI, Macklaim JM, Wuyts S, Verhoeven T, Vanderleyden J, Gloor G, Lebeer S, Reid G. 2018. Comparative genomic and phenotypic analysis of the vaginal probiotic Lactobacillus rhamnosus GR-1. Front Microbiol 9:1278.
    257.
    Grangette C, Nutten S, Palumbo E, Morath S, Hermann C, Dewulf J, Pot B, Hartung T, Hols P, Mercenier A. 2005. Enhanced antiinflammatory capacity of a Lactobacillus plantarum mutant synthesizing modified teichoic acids. Proc Natl Acad Sci U S A 102:10321–10326.
    258.
    Claes IJJ, De Keersmaecker SCJ, Vanderleyden J, Lebeer S. 2011. Lessons from probiotic-host interaction studies in murine models of experimental colitis. Mol Nutr Food Res 55:1441–1453.
    259.
    Matsuguchi T, Takagi A, Matsuzaki T, Nagaoka M, Ishikawa K, Yokokura T, Yoshikai Y. 2003. Lipoteichoic acids from Lactobacillus strains elicit strong tumor necrosis factor alpha-inducing activities in macrophages through Toll-like receptor 2. Clin Diagn Lab Immunol 10:259–266.
    260.
    Mohamadzadeh M, Pfeiler EA, Brown JB, Zadeh M, Gramarossa M, Managlia E, Bere P, Sarraj B, Khan MW, Pakanati KC, Ansari MJ, O'Flaherty S, Barrett T, Klaenhammer TR. 2011. Regulation of induced colonic inflammation by Lactobacillus acidophilus deficient in lipoteichoic acid. Proc Natl Acad Sci U S A 108(Suppl 1):4623–4630.
    261.
    Yasuda E, Serata M, Sako T. 2008. Suppressive effect on activation of macrophages by Lactobacillus casei strain shirota genes determining the synthesis of cell wall-associated polysaccharides. Appl Environ Microbiol 74:4746–4755.
    262.
    Remus DM, van Kranenburg R, van Swam II, Taverne N, Bongers RS, Wels M, Wells JM, Bron PA, Kleerebezem M. 2012. Impact of 4 Lactobacillus plantarum capsular polysaccharide clusters on surface glycan composition and host cell signaling. Microb Cell Fact 11:149.
    263.
    Kant R, de Vos WM, Palva A, Satokari R. 2014. Immunostimulatory CpG motifs in the genomes of gut bacteria and their role in human health and disease. J Med Microbiol 63:293–308.
    264.
    von Schillde M-A, Hörmannsperger G, Weiher M, Alpert C-A, Hahne H, Bäuerl C, Van Huynegem K, Steidler L, Hrncir T, Pérez-Martínez G, Kuster B, Haller D. 2012. Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines. Cell Host Microbe 11:387–396.
    265.
    Sun Z, Harris HMB, McCann A, Guo C, Argimón S, Zhang W, Yang X, Jeffery IB, Cooney JC, Kagawa TF, Liu W, Song Y, Salvetti E, Wrobel A, Rasinkangas P, Parkhill J, Rea MC, O’Sullivan O, Ritari J, Douillard FP, Paul Ross R, Yang R, Briner AE, Felis GE, de Vos WM, Barrangou R, Klaenhammer TR, Caufield PW, Cui Y, Zhang H, O’Toole PW. 2015. Expanding the biotechnology potential of lactobacilli through comparative genomics of 213 strains and associated genera. Nat Commun 6:8322.
    266.
    Vinolo MAR, Rodrigues HG, Hatanaka E, Sato FT, Sampaio SC, Curi R. 2011. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J Nutr Biochem 22:849–855.
    267.
    Vinolo MAR, Rodrigues HG, Nachbar RT, Curi R. 2011. Regulation of inflammation by short chain fatty acids. Nutrients 3:858–876.
    268.
    Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Di Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, Mackay CR. 2009. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461:1282–1286.
    269.
    Park J-S, Lee E-J, Lee J-C, Kim W-K, Kim H-S. 2007. Anti-inflammatory effects of short chain fatty acids in IFN-γ-stimulated RAW 264.7 murine macrophage cells: involvement of NF-κB and ERK signaling pathways. Int Immunopharmacol 7:70–77.
    270.
    Mountzouris KC, Kotzampassi K, Tsirtsikos P, Kapoutzis K, Fegeros K. 2009. Effects of Lactobacillus acidophilus on gut microflora metabolic biomarkers in fed and fasted rats. Clin Nutr 28:318–324.
    271.
    Yamano T, Iino H, Takada M, Blum S, Rochat F, Fukushima Y. 2006. Improvement of the human intestinal flora by ingestion of the probiotic strain Lactobacillus johnsonii La1. Br J Nutr 95:303–312.
    272.
    Louis P, Flint HJ. 2009. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett 294:1–8.
    273.
    Lewnard JA, Givon-Lavi N, Tähtinen PA, Dagan R. 2018. Pneumococcal phenotype and interaction with nontypeable Haemophilus influenzae as determinants of otitis media progression. Infect Immun 86:e00727-17.
    274.
    Eythorsson E, Hrafnkelsson B, Erlendsdóttir H, Gudmundsson SA, Kristinsson KG, Haraldsson Á. 2018. Decreased acute otitis media with treatment failure after introduction of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine. Pediatr Infect Dis J 37:361–366.
    275.
    de Vrese M, Rautenberg P, Laue C, Koopmans M, Herremans T, Schrezenmeir J. 2005. Probiotic bacteria stimulate virus-specific neutralizing antibodies following a booster polio vaccination. Eur J Nutr 44:406–413.
    276.
    Isolauri E, Joensuu J, Suomalainen H, Luomala M, Vesikari T. 1995. Improved immunogenicity of oral D x RRV reassortant rotavirus vaccine. Vaccine 13:310–312.
    277.
    Davidson L, Fiorino A-M, Snydman D, Hibberd P. 2011. Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial. Eur J Clin Nutr 65:501–507.
    278.
    Boyle RJ, Ismail IH, Kivivuori S, Licciardi PV, Robins-Browne RM, Mah L-J, Axelrad C, Moore S, Donath S, Carlin JB, Lahtinen SJ, Tang M. 2011. Lactobacillus GG treatment during pregnancy for the prevention of eczema: a randomized controlled trial. Allergy 66:509–516.
    279.
    Amerighi F, Valeri M, Donnarumma D, Maccari S, Moschioni M, Taddei A, Lapazio L, Pansegrau W, Buccato S, De Angelis G, Ruggiero P, Masignani V, Soriani M, Pezzicoli A. 2016. Identification of a monoclonal antibody against pneumococcal pilus 1 ancillary protein impairing bacterial adhesion to human epithelial cells. J Infect Dis 213:516–522.
    280.
    Pettigrew MM, Gent JF, Revai K, Patel JA, Chonmaitree T. 2008. Microbial interactions during upper respiratory tract infections. Emerg Infect Dis 14:1584–1591.
    281.
    Sanders ME, Benson A, Lebeer S, Merenstein DJ, Klaenhammer TR. 2018. Shared mechanisms among probiotic taxa: implications for general probiotic claims. Curr Opin Biotechnol 49:207–216.
    282.
    Chonmaitree T, Jennings K, Golovko G, Khanipov K, Pimenova M, Patel JA, McCormick DP, Loeffelholz MJ, Fofanov Y. 2017. Nasopharyngeal microbiota in infants and changes during viral upper respiratory tract infection and acute otitis media. PLoS One 12:e0180630.

    Author Bios

    Marianne F. L. van den Broek
    Environmental Ecology and Applied Microbiology Research Group, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium
    Marianne F. L. van den Broek, Ph.D., completed her studies of Bioscience Engineering with a focus on cell and gene technology at the Catholic University of Leuven in 2012. In 2013, Dr. Ir. van den Broek started work on a Ph.D. at the University of Antwerp in the laboratory of Prof. Dr. Ir. Sarah Lebeer, researching the in vitro and in vivo probiotic potential of Lactobacillus spp. for otitis media, which she successfully finalized in February 2018. At the moment, she is working as a postdoctoral research scientist in this laboratory, with a focus on the potential of several probiotics for upper respiratory tract diseases and the impact on the local microbiome.
    Ilke De Boeck
    Environmental Ecology and Applied Microbiology Research Group, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium
    Ilke De Boeck completed her bachelor’s degree in bioscience engineering with a focus on cell and gene technology at the University of Antwerp in 2012 and graduated from her master’s degree program in bioscience engineering, cell and gene technology, at the Catholic University of Leuven in 2014. In 2014, Ir. De Boeck started her Ph.D. at the University of Antwerp in the laboratory of Prof. Dr. Ir. Sarah Lebeer with copromotor Prof. Dr. Olivier Vanderveken, researching the potential of probiotics for chronic rhinosinusitis. She is focusing on the characterization of the upper respiratory tract (URT) microbiome in adults using Illumina MiSeq sequencing and the cultivation of lactic acid bacteria from the URT to explore their potential as URT probiotics.
    Filip Kiekens
    Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium
    Filip Kiekens, Pharm.D., completed his studies in pharmaceutical sciences at the University of Ghent. In 2000, Prof. Dr. Kiekens finalized his Ph.D. in the Laboratory of Pharmaceutical Technology at the same university. After obtaining a Ph.D., he worked for 12 years in pharmaceutical product research and development (multinational and small and medium enterprises [SME]). He has headed an academic research group in pharmaceutical technology for the last 5 years, with specific interest in applying pharmaceutical technological processes to a wide field of applications.
    An Boudewyns
    Department of Otorhinolaryngology, Head and Neck Surgery, Antwerp University Hospital, Edegem, Belgium
    An Boudewyns, M.D., completed her studies in Medicine at the University of Antwerp, Belgium. Prof. Dr. Boudewyns obtained the degree of doctor in medical sciences at the University of Antwerp, Belgium, in 1999 and has been a Guest Lecturer at the Faculty of Medicine, Translational Neurosciences, at the University of Antwerp, Belgium, since October 2002. She is a coauthor of 103 peer-reviewed publications. She has been a staff member at the Department of Otorhinolaryngology, Head and Neck Surgery, of the Antwerp University Hospital since 2001 and has a subspecialty in pediatric ear, nose, and throat (ENT) surgery. As a pediatric ENT surgeon, she has a major interest in upper airway problems and infections in children, and she has been working in the area of the upper airway microbiome since 2016.
    Olivier M. Vanderveken
    Department of Otorhinolaryngology, Head and Neck Surgery, Antwerp University Hospital, Edegem, Belgium
    Department of Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
    Olivier M. Vanderveken, M.D., is a full-time ear, nose, and throat (ENT), head, and neck surgeon at the Antwerp University Hospital in Belgium, where he holds an appointment as Chair of the department. Prof. Dr. Vanderveken holds a position as Professor at the Faculty of Medicine of the University of Antwerp. Prof. Dr. Vanderveken received his medical degree from the University of Antwerp in 2001. He completed his residency at the Antwerp University Hospitals. In 2007, he obtained a Ph.D. in medical sciences. His research is in the area of sleep-disordered breathing and the microbiota of the upper respiratory tract. Prof. Dr. Vanderveken has coauthored several professional scientific publications in high-impact peer-reviewed journals. Prof. Dr. Vanderveken has been the recipient of several national and international scientific awards. He holds a Senior Clinical Investigator Fellowship at the Research Foundation Flanders (FWO) in Belgium that supports him in pursuing a full-fledged career in translational research.
    Environmental Ecology and Applied Microbiology Research Group, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium
    Sarah Lebeer is an Associate Professor in Microbiology and Biotechnology at the Bioscience Engineering Department of the University of Antwerp (Belgium). Prof. Dr. Ir. Lebeer obtained her Ph.D. in Bioscience Engineering from the KU Leuven (Belgium) in 2008 after receiving a Ph.D. scholarship from the Research Foundation Flanders (FWO). She specialized in bacterial genetics and functional characterization of probiotics, their cell wall molecules, and associated immunological effects. From 2008 to 2011, she was a postdoctoral research scientist studying the mucosal immunology of probiotics, including a shift of her research interests from the gut to the urogenital tract. When she started her own laboratory as tenure track professor at the University of Antwerp in 2011, she further extended her research interests on probiotics and the human microbiome toward the upper respiratory tract. For example, she coordinates a large project on defining the future of probiotics for respiratory tract diseases (www.procureproject.be).

    Information & Contributors

    Information

    Published In

    Clinical Microbiology Reviews
    Volume 32Number 418 September 2019
    eLocator: e00010-18

    History

    Published online: 3 July 2019

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    KEYWORDS

    1. Haemophilus influenzae
    2. Lactobacillus
    3. microbiome
    4. Moraxella catarrhalis
    5. otitis media
    6. probiotics
    7. Streptococcus pneumoniae

    Contributors

    Authors

    Marianne F. L. van den Broek
    Environmental Ecology and Applied Microbiology Research Group, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium
    Ilke De Boeck
    Environmental Ecology and Applied Microbiology Research Group, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium
    Filip Kiekens
    Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium
    An Boudewyns
    Department of Otorhinolaryngology, Head and Neck Surgery, Antwerp University Hospital, Edegem, Belgium
    Olivier M. Vanderveken
    Department of Otorhinolaryngology, Head and Neck Surgery, Antwerp University Hospital, Edegem, Belgium
    Department of Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
    Environmental Ecology and Applied Microbiology Research Group, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium

    Notes

    Address correspondence to Sarah Lebeer, [email protected].

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  • Clinical Microbiology ReviewsArticle
    A Microbiological Revolution Meets an Ancient Disease: Improving the Management of Tuberculosis with Genomics

    A Microbiological Revolution Meets an Ancient Disease: Improving the Management of Tuberculosis with Genomics

    SUMMARY

    Tuberculosis (TB) is an ancient disease with an enormous global impact. Despite declining global incidence, the diagnosis, phenotyping, and epidemiological investigation of TB require significant clinical microbiology laboratory resources. Current methods for the detection and characterization of Mycobacterium tuberculosis consist of a series of laboratory tests varying in speed and performance, each of which yields incremental information about the disease. Since the sequencing of the first M. tuberculosis genome in 1998, genomic tools have aided in the diagnosis, treatment, and control of TB. Here we summarize genomics-based methods that are positioned to be introduced in the modern clinical TB laboratory, and we highlight how recent advances in genomics will improve the detection of antibiotic resistance-conferring mutations and the understanding of M. tuberculosis transmission dynamics and epidemiology. We imagine the future TB clinic as one that relies heavily on genomic interrogation of the M. tuberculosis isolate, allowing for more rapid diagnosis of TB and real-time monitoring of outbreak emergence.

    REFERENCES

    1.
    WHO. 2013. Global tuberculosis report 2013. WHO, Geneva, Switzerland.
    2.
    Comas I, Coscolla M, Luo T, Borrell S, Holt KE, Kato-Maeda M, Parkhill J, Malla B, Berg S, Thwaites G, Yeboah-Manu D, Bothamley G, Mei J, Wei L, Bentley S, Harris SR, Niemann S, Diel R, Aseffa A, Gao Q, Young D, Gagneux S. 2013. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nat Genet 45:1176–1182.
    3.
    Brosch R, Gordon SV, Marmiesse M, Brodin P, Buchrieser C, Eiglmeier K, Garnier T, Gutierrez C, Hewinson G, Kremer K, Parsons LM, Pym AS, Samper S, van Soolingen D, Cole ST. 2002. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc Natl Acad Sci U S A 99:3684–3689.
    4.
    Bos KI, Harkins KM, Herbig A, Coscolla M, Weber N, Comas I, Forrest SA, Bryant JM, Harris SR, Schuenemann VJ, Campbell TJ, Majander K, Wilbur AK, Guichon RA, Wolfe Steadman DL, Cook DC, Niemann S, Behr MA, Zumarraga M, Bastida R, Huson D, Nieselt K, Young D, Parkhill J, Buikstra JE, Gagneux S, Stone AC, Krause J. 2014. Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis. Nature 514:494–497.
    5.
    Mehta JB, Dutt A, Harvill L, Mathews KM. 1991. Epidemiology of extrapulmonary tuberculosis. a comparative analysis with pre-AIDS era. Chest J 99:1134–1138.
    6.
    Zumla A, Raviglione M, Hafner R, von Reyn CF. 2013. Tuberculosis. N Engl J Med 368:745–755.
    7.
    Raviglione M, Marais B, Floyd K, Lönnroth K, Getahun H, Migliori GB, Harries AD, Nunn P, Lienhardt C, Graham S, Chakaya J, Weyer K, Cole S, Kaufmann SH, Zumla A. 2012. Scaling up interventions to achieve global tuberculosis control: progress and new developments. Lancet 379:1902–1913.
    8.
    Supply P, Marceau M, Mangenot S, Roche D, Rouanet C, Khanna V, Majlessi L, Criscuolo A, Tap J, Pawlik A, Fiette L, Orgeur M, Fabre M, Parmentier C, Frigui W, Simeone R, Boritsch EC, Debrie A-S, Willery E, Walker D, Quail MA, Ma L, Bouchier C, Salvignol G, Sayes F, Cascioferro A, Seemann T, Barbe V, Locht C, Gutierrez M-C, Leclerc C, Bentley SD, Stinear TP, Brisse S, Médigue C, Parkhill J, Cruveiller S, Brosch R. 2013. Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis. Nat Genet 45:172–179.
    9.
    Boritsch EC, Supply P, Honoré N, Seeman T, Stinear TP, Brosch R. 2014. A glimpse into the past and predictions for the future: the molecular evolution of the tuberculosis agent. Mol Microbiol 93:835–852.
    10.
    Van Soolingen D, van der Zanden AG, de Haas PE, Noordhoek GT, Kiers A, Foudraine NA, Portaels F, Kolk AH, Kremer K, van Embden JD. 1998. Diagnosis of Mycobacterium microti infections among humans by using novel genetic markers. J Clin Microbiol 36:1840–1845.
    11.
    Rodríguez E, Sánchez LP, Pérez S, Herrera L, Jiménez MS, Samper S, Iglesias MJ. 2009. Human tuberculosis due to Mycobacterium bovis and M. caprae in Spain, 2004–2007. Int J Tuberc Lung Dis 13:1536–1541.
    12.
    Van Ingen J, Rahim Z, Mulder A, Boeree MJ, Simeone R, Brosch R, van Soolingen D. 2012. Characterization of Mycobacterium orygis as M. tuberculosis complex subspecies. Emerg Infect Dis 18:653–655.
    13.
    Kiers A, Klarenbeek A, Mendelts B, Van Soolingen D, Koëter G. 2008. Transmission of Mycobacterium pinnipedii to humans in a zoo with marine mammals. Int J Tuberc Lung Dis 12:1469–1473.
    14.
    Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream M-A, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537–544.
    15.
    Mostowy S, Behr MA. 2005. The origin and evolution of Mycobacterium tuberculosis. Clin Chest Med 26:207–216.
    16.
    Coscolla M, Gagneux S. 2010. Does M. tuberculosis genomic diversity explain disease diversity? Drug Discov Today Dis Mech 7:e43–e59.
    17.
    Tortoli E. 2014. Microbiological features and clinical relevance of new species of the genus Mycobacterium. Clin Microbiol Rev 27:727–752.
    18.
    Liu L, Li Y, Li S, Hu N, He Y, Pong R, Lin D, Lu L, Law M. 2012. Comparison of next-generation sequencing systems. J Biomed Biotechnol 2012:251364.
    19.
    Didelot X, Bowden R, Wilson DJ, Peto TEA, Crook DW. 2012. Transforming clinical microbiology with bacterial genome sequencing. Nat Rev Genet 13:601–612.
    20.
    Yin X, Zheng L, Lin L, Hu Y, Zheng F, Hu Y, Wang Q. 2013. Commercial MPT64-based tests for rapid identification of Mycobacterium tuberculosis complex: a meta-analysis. J Infect 67:369–377.
    21.
    Roberts SA, Lowe O, Pandey S, Williamson DA, Newton S, Vaughan R. 2012. Comparison of the MGIT TBc immunochromatographic assay with the Accuprobe Gen-Probe TB assay for identification of Mycobacterium tuberculosis complex: results from a low-burden tuberculosis setting. Diagn Microbiol Infect Dis 74:415–416.
    22.
    Scott LE, McCarthy K, Gous N, Nduna M, Van Rie A, Sanne I, Venter WF, Duse A, Stevens W. 2011. Comparison of Xpert MTB/RIF with other nucleic acid technologies for diagnosing pulmonary tuberculosis in a high HIV prevalence setting: a prospective study. PLoS Med 8:e1001061.
    23.
    McNabb A, Adie K, Rodrigues M, Black WA, Isaac-Renton J. 2006. Direct identification of mycobacteria in primary liquid detection media by partial sequencing of the 65-kilodalton heat shock protein gene. J Clin Microbiol 44:60–66.
    24.
    Helb D, Jones M, Story E, Boehme C, Wallace E, Ho K, Kop J, Owens MR, Rodgers R, Banada P, Safi H, Blakemore R, Lan NTN, Jones-López EC, Levi M, Burday M, Ayakaka I, Mugerwa RD, McMillan B, Winn-Deen E, Christel L, Dailey P, Perkins MD, Persing DH, Alland D. 2010. Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology. J Clin Microbiol 48:229–237.
    25.
    Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, Allen J, Tahirli R, Blakemore R, Rustomjee R, Milovic A, Jones M, O'Brien SM, Persing DH, Ruesch-Gerdes S, Gotuzzo E, Rodrigues C, Alland D, Perkins MD. 2010. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med 363:1005–1015.
    26.
    Walusimbi S, Bwanga F, De Costa A, Haile M, Joloba M, Hoffner S. 2013. Meta-analysis to compare the accuracy of GeneXpert, MODS and the WHO 2007 algorithm for diagnosis of smear-negative pulmonary tuberculosis. BMC Infect Dis 13:507.
    27.
    Albert H, Ademun PJ, Lukyamuzi G, Nyesiga B, Manabe Y, Joloba M, Wilson S, Perkins MD. 2011. Feasibility of magnetic bead technology for concentration of mycobacteria in sputum prior to fluorescence microscopy. BMC Infect Dis 11:125.
    28.
    Ghodbane R, Drancourt M. 2013. Magnetic bead protocol for culturing Mycobacterium tuberculosis from sputum specimens. J Clin Microbiol 51:1578–1579.
    29.
    Liu J, Sun Z-Q, Pei H, Zhang S-L, Zhang S-L, Wilson S, De Smet K, Cerullakandiyil N, Thayyullathil T, AL-Suwaidi Z, Song Y-Z. 2013. Increased case finding of tuberculosis from sputum and sputum deposits after magnetic bead concentration of mycobacteria. J Microbiol Methods 93:144–147.
    30.
    Elitas M, Martinez-Duarte R, Dhar N, McKinney JD, Renaud P. 2014. Dielectrophoresis-based purification of antibiotic-treated bacterial subpopulations. Lab Chip 14:1850–1857.
    31.
    Wang S, Inci F, De Libero G, Singhal A, Demirci U. 2013. Point-of-care assays for tuberculosis: role of nanotechnology/microfluidics. Biotechnol Adv 31:438–449.
    32.
    Doughty EL, Sergeant MJ, Adetifa I, Antonio M, Pallen MJ. 2014. Culture-independent detection and characterisation of Mycobacterium tuberculosis and M. africanum in sputum samples using shotgun metagenomics on a benchtop sequencer. PeerJ 2:e585.
    33.
    Branton D, Deamer DW, Marziali A, Bayley H, Benner SA, Butler T, Di Ventra M, Garaj S, Hibbs A, Huang X, Jovanovich SB, Krstic PS, Lindsay S, Ling XS, Mastrangelo CH, Meller A, Oliver JS, Pershin YV, Ramsey JM, Riehn R, Soni GV, Tabard-Cossa V, Wanunu M, Wiggin M, Schloss JA. 2008. The potential and challenges of nanopore sequencing. Nat Biotechnol 26:1146–1153.
    34.
    Macaulay IC, Voet T. 2014. Single cell genomics: advances and future perspectives. PLoS Genet 10:e1004126.
    35.
    Ling DI, Zwerling AA, Pai M. 2008. Rapid diagnosis of drug-resistant TB using line probe assays: from evidence to policy. Expert Rev Respir Med 2:583–588.
    36.
    Rossau R, Traore H, De Beenhouwer H, Mijs W, Jannes G, De Rijk P, Portaels F. 1997. Evaluation of the INNO-LiPA Rif.TB assay, a reverse hybridization assay for the simultaneous detection of Mycobacterium tuberculosis complex and its resistance to rifampin. Antimicrob Agents Chemother 41:2093–2098.
    37.
    Hillemann D, Rüsch-Gerdes S, Richter E. 2007. Evaluation of the GenoType MTBDRplus assay for rifampin and isoniazid susceptibility testing of Mycobacterium tuberculosis strains and clinical specimens. J Clin Microbiol 45:2635–2640.
    38.
    Campbell PJ, Morlock GP, Sikes RD, Dalton TL, Metchock B, Starks AM, Hooks DP, Cowan LS, Plikaytis BB, Posey JE. 2011. Molecular detection of mutations associated with first- and second-line drug resistance compared with conventional drug susceptibility testing of Mycobacterium tuberculosis. Antimicrob Agents Chemother 55:2032–2041.
    39.
    Zhang H, Li D, Zhao L, Fleming J, Lin N, Wang T, Liu Z, Li C, Galwey N, Deng J, Zhou Y, Zhu Y, Gao Y, Wang T, Wang S, Huang Y, Wang M, Zhong Q, Zhou L, Chen T, Zhou J, Yang R, Zhu G, Hang H, Zhang J, Li F, Wan K, Wang J, Zhang X-E, Bi L. 2013. Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance. Nat Genet 45:1255–1260.
    40.
    Farhat MR, Shapiro BJ, Kieser KJ, Sultana R, Jacobson KR, Victor TC, Warren RM, Streicher EM, Calver A, Sloutsky A, Kaur D, Posey JE, Plikaytis B, Oggioni MR, Gardy JL, Johnston JC, Rodrigues M, Tang PKC, Kato-Maeda M, Borowsky ML, Muddukrishna B, Kreiswirth BN, Kurepina N, Galagan J, Gagneux S, Birren B, Rubin EJ, Lander ES, Sabeti PC, Murray M. 2013. Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis. Nat Genet 45:1183–1189.
    41.
    Safi H, Lingaraju S, Amin A, Kim S, Jones M, Holmes M, McNeil M, Peterson SN, Chatterjee D, Fleischmann R, Alland D. 2013. Evolution of high-level ethambutol-resistant tuberculosis through interacting mutations in decaprenylphosphoryl-β-d-arabinose biosynthetic and utilization pathway genes. Nat Genet 45:1190–1197.
    42.
    Casali N, Nikolayevskyy V, Balabanova Y, Harris SR, Ignatyeva O, Kontsevaya I, Corander J, Bryant J, Parkhill J, Nejentsev S, Horstmann RD, Brown T, Drobniewski F. 2014. Evolution and transmission of drug-resistant tuberculosis in a Russian population. Nat Genet 46:279–286.
    43.
    Eldholm V, Norheim G, von der Lippe B, Kinander W, Dahle UR, Caugant DA, Mannsåker T, Mengshoel AT, Dyrhol-Riise AM, Balloux F. 2014. Evolution of extensively drug-resistant Mycobacterium tuberculosis from a susceptible ancestor in a single patient. Genome Biol 15:490.
    44.
    Andries K, Verhasselt P, Guillemont J, Göhlmann HWH, Neefs J-M, Winkler H, Van Gestel J, Timmerman P, Zhu M, Lee E, Williams P, de Chaffoy D, Huitric E, Hoffner S, Cambau E, Truffot-Pernot C, Lounis N, Jarlier V. 2005. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307:223–227.
    45.
    Clark TG, Mallard K, Coll F, Preston M, Assefa S, Harris D, Ogwang S, Mumbowa F, Kirenga B, O'Sullivan DM, Okwera A, Eisenach KD, Joloba M, Bentley SD, Ellner JJ, Parkhill J, Jones-López EC, McNerney R. 2013. Elucidating emergence and transmission of multidrug-resistant tuberculosis in treatment experienced patients by whole genome sequencing. PLoS One 8:e83012.
    46.
    De Vos M, Muller B, Borrell S, Black PA, van Helden PD, Warren RM, Gagneux S, Victor TC. 2013. Putative compensatory mutations in the rpoC gene of rifampin-resistant Mycobacterium tuberculosis are associated with ongoing transmission. Antimicrob Agents Chemother 57:827–832.
    47.
    Brandis G, Hughes D. 2013. Genetic characterization of compensatory evolution in strains carrying rpoB Ser531Leu, the rifampicin resistance mutation most frequently found in clinical isolates. J Antimicrob Chemother 68:2493–2497.
    48.
    Comas I, Borrell S, Roetzer A, Rose G, Malla B, Kato-Maeda M, Galagan J, Niemann S, Gagneux S. 2012. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat Genet 44:106–110.
    49.
    Aguilar D, Hanekom M, Mata D, Gey van Pittius NC, van Helden PD, Warren RM, Hernandez-Pando R. 2010. Mycobacterium tuberculosis strains with the Beijing genotype demonstrate variability in virulence associated with transmission. Tuberculosis (Edinb) 90:319–325.
    50.
    Reiling N, Homolka S, Walter K, Brandenburg J, Niwinski L, Ernst M, Herzmann C, Lange C, Diel R, Ehlers S, Niemann S. 2013. Clade-specific virulence patterns of Mycobacterium tuberculosis complex strains in human primary macrophages and aerogenically infected mice. mBio 4:e00250-13.
    51.
    Ford CB, Shah RR, Maeda MK, Gagneux S, Murray MB, Cohen T, Johnston JC, Gardy J, Lipsitch M, Fortune SM. 2013. Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis. Nat Genet 45:784–790.
    52.
    Trauner A, Borrell S, Reither K, Gagneux S. 2014. Evolution of drug resistance in tuberculosis: recent progress and implications for diagnosis and therapy. Drugs 74:1063–1072.
    53.
    Köser CU, Bryant JM, Becq J, Török ME, Ellington MJ, Marti-Renom MA, Carmichael AJ, Parkhill J, Smith GP, Peacock SJ. 2013. Whole-genome sequencing for rapid susceptibility testing of M. tuberculosis. N Engl J Med 369:290–292.
    54.
    Kim SJ. 2005. Drug-susceptibility testing in tuberculosis: methods and reliability of results. Eur Respir J 25:564–569.
    55.
    Maruri F, Sterling TR, Kaiga AW, Blackman A, van der Heijden YF, Mayer C, Cambau E, Aubry A. 2012. A systematic review of gyrase mutations associated with fluoroquinolone-resistant Mycobacterium tuberculosis and a proposed gyrase numbering system. J Antimicrob Chemother 67:819–831.
    56.
    Laurenzo D, Mousa SA. 2011. Mechanisms of drug resistance in Mycobacterium tuberculosis and current status of rapid molecular diagnostic testing. Acta Trop 119:5–10.
    57.
    Shafer RW. 2006. Rationale and uses of a public HIV drug-resistance database. J Infect Dis 194(Suppl 1):S51–S58.
    58.
    Sandgren A, Strong M, Muthukrishnan P, Weiner BK, Church GM, Murray MB. 2009. Tuberculosis drug resistance mutation database. PLoS Med 6:e2.
    59.
    Flandrois J-P, Lina G, Dumitrescu O. 2014. MUBII-TB-DB: a database of mutations associated with antibiotic resistance in Mycobacterium tuberculosis. BMC Bioinformatics 15:107.
    60.
    Kasaie P, Andrews JR, Kelton WD, Dowdy DW. 2014. Timing of tuberculosis transmission and the impact of household contact tracing. An agent-based simulation model. Am J Respir Crit Care Med 189:845–852.
    61.
    Shrivastava SR, Shrivastava PS, Ramasamy J. 2014. Assessing the utility of contact tracing in reducing the magnitude of tuberculosis. Infect Ecol Epidemiol 4:10.3402/iee.v4.25265.
    62.
    Gardy JL, Johnston JC, Sui SJH, Cook VJ, Shah L, Brodkin E, Rempel S, Moore R, Zhao Y, Holt R, Varhol R, Birol I, Lem M, Sharma MK, Elwood K, Jones SJM, Brinkman FSL, Brunham RC, Tang P. 2011. Whole-genome sequencing and social-network analysis of a tuberculosis outbreak. N Engl J Med 364:730–739.
    63.
    Walker TM, Ip CLC, Harrell RH, Evans JT, Kapatai G, Dedicoat MJ, Eyre DW, Wilson DJ, Hawkey PM, Crook DW, Parkhill J, Harris D, Walker AS, Bowden R, Monk P, Smith EG, Peto TEA. 2013. Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis 13:137–146.
    64.
    Streicher EM, Victor TC, van der Spuy G, Sola C, Rastogi N, van Helden PD, Warren RM. 2007. Spoligotype signatures in the Mycobacterium tuberculosis complex. J Clin Microbiol 45:237–240.
    65.
    Supply P, Allix C, Lesjean S, Cardoso-Oelemann M, Rüsch-Gerdes S, Willery E, Savine E, de Haas P, van Deutekom H, Roring S, Bifani P, Kurepina N, Kreiswirth B, Sola C, Rastogi N, Vatin V, Gutierrez MC, Fauville M, Niemann S, Skuce R, Kremer K, Locht C, van Soolingen D. 2006. Proposal for standardization of optimized mycobacterial interspersed repetitive-unit–variable-number tandem repeat typing of Mycobacterium tuberculosis. J Clin Microbiol 44:4498–4510.
    66.
    Torrea G, Levee G, Grimont P, Martin C, Chanteau S, Gicquel B. 1995. Chromosomal DNA fingerprinting analysis using the insertion sequence IS6110 and the repetitive element DR as strain-specific markers for epidemiological study of tuberculosis in French Polynesia. J Clin Microbiol 33:1899–1904.
    67.
    Köser CU, Ellington MJ, Cartwright EJP, Gillespie SH, Brown NM, Farrington M, Holden MTG, Dougan G, Bentley SD, Parkhill J, Peacock SJ. 2012. Routine use of microbial whole genome sequencing in diagnostic and public health microbiology. PLoS Pathog 8:e1002824.
    68.
    Sola C, Filliol I, Legrand E, Lesjean S, Locht C, Supply P, Rastogi N. 2003. Genotyping of the Mycobacterium tuberculosis complex using MIRUs: association with VNTR and spoligotyping for molecular epidemiology and evolutionary genetics. Infect Genet Evol 3:125–133.
    69.
    Niemann S, Köser CU, Gagneux S, Plinke C, Homolka S, Bignell H, Carter RJ, Cheetham RK, Cox A, Gormley NA, Kokko-Gonzales P, Murray LJ, Rigatti R, Smith VP, Arends FPM, Cox HS, Smith G, Archer JAC. 2009. Genomic diversity among drug sensitive and multidrug resistant isolates of Mycobacterium tuberculosis with identical DNA fingerprints. PLoS One 4:e7407.
    70.
    Schurch AC, Kremer K, Daviena O, Kiers A, Boeree MJ, Siezen RJ, van Soolingen D. 2010. High-resolution typing by integration of genome sequencing data in a large tuberculosis cluster. J Clin Microbiol 48:3403–3406.
    71.
    Roetzer A, Diel R, Kohl TA, Rückert C, Nübel U, Blom J, Wirth T, Jaenicke S, Schuback S, Rüsch-Gerdes S, Supply P, Kalinowski J, Niemann S. 2013. Whole genome sequencing versus traditional genotyping for investigation of a Mycobacterium tuberculosis outbreak: a longitudinal molecular epidemiological study. PLoS Med 10:e1001387.
    72.
    Kato-Maeda M, Ho C, Passarelli B, Banaei N, Grinsdale J, Flores L, Anderson J, Murray M, Rose G, Kawamura LM, Pourmand N, Tariq MA, Gagneux S, Hopewell PC. 2013. Use of whole genome sequencing to determine the microevolution of Mycobacterium tuberculosis during an outbreak. PLoS One 8:e58235.
    73.
    Luo T, Yang C, Peng Y, Lu L, Sun G, Wu J, Jin X, Hong J, Li F, Mei J, DeRiemer K, Gao Q. 2014. Whole-genome sequencing to detect recent transmission of Mycobacterium tuberculosis in settings with a high burden of tuberculosis. Tuberculosis (Edinb) 94:434–440.
    74.
    Jamieson FB, Teatero S, Guthrie JL, Neemuchwala A, Fittipaldi N, Mehaffy C. 2014. Whole-genome sequencing of the Mycobacterium tuberculosis Manila sublineage results in less clustering and better resolution than mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) typing and spoligotyping. J Clin Microbiol 52:3795–3798.
    75.
    Mehaffy C, Guthrie JL, Alexander DC, Stuart R, Rea E, Jamieson FB. 2014. Marked microevolution of a unique Mycobacterium tuberculosis strain in 17 years of ongoing transmission in a high risk population. PLoS One 9:e112928.
    76.
    Stucki D, Ballif M, Bodmer T, Coscolla M, Maurer A-M, Droz S, Butz C, Borrell S, Längle C, Feldmann J, Furrer H, Mordasini C, Helbling P, Rieder HL, Egger M, Gagneux S, Fenner L. 30 October 2014. Tracking a tuberculosis outbreak over 21 years: strain-specific single-nucleotide polymorphism typing combined with targeted whole-genome sequencing. J Infect Dis doi:
    77.
    Schürch AC, Kremer K, Kiers A, Daviena O, Boeree MJ, Siezen RJ, Smith NH, van Soolingen D. 2010. The tempo and mode of molecular evolution of Mycobacterium tuberculosis at patient-to-patient scale. Infect Genet Evol 10:108–114.
    78.
    Török ME, Reuter S, Bryant J, Köser CU, Stinchcombe SV, Nazareth B, Ellington MJ, Bentley SD, Smith GP, Parkhill J, Peacock SJ. 2013. Rapid whole-genome sequencing for investigation of a suspected tuberculosis outbreak. J Clin Microbiol 51:611–614.
    79.
    Walker TM, Lalor MK, Broda A, Ortega LS, Morgan M, Parker L, Churchill S, Bennett K, Golubchik T, Giess AP, Del Ojo Elias C, Jeffery KJ, Bowler ICJW, Laurenson IF, Barrett A, Drobniewski F, McCarthy ND, Anderson LF, Abubakar I, Thomas HL, Monk P, Smith EG, Walker AS, Crook DW, Peto TEA, Conlon CP. 2014. Assessment of Mycobacterium tuberculosis transmission in Oxfordshire, UK, 2007–12, with whole pathogen genome sequences: an observational study. Lancet Respir Med 2:285–292.
    80.
    Didelot X, Gardy J, Colijn C. 2014. Bayesian inference of infectious disease transmission from whole-genome sequence data. Mol Biol Evol 31:1869–1879.
    81.
    Kohl TA, Diel R, Harmsen D, Rothgänger J, Meywald Walter K, Merker M, Weniger T, Niemann S. 2014. Whole genome based Mycobacterium tuberculosis surveillance: a standardized, portable and expandable approach. J Clin Microbiol 52:2479–2486.
    82.
    Coll F, Mallard K, Preston MD, Bentley S, Parkhill J, McNerney R, Martin N, Clark TG. 2012. SpolPred: rapid and accurate prediction of Mycobacterium tuberculosis spoligotypes from short genomic sequences. Bioinformatics 28:2991–2993.
    83.
    Halachev MR, Chan JZ-M, Constantinidou CI, Cumley N, Bradley C, Smith-Banks M, Oppenheim B, Pallen MJ. 2014. Genomic epidemiology of a protracted hospital outbreak caused by multidrug-resistant Acinetobacter baumannii in Birmingham, England. Genome Med 6:70.
    84.
    Snitkin ES, Zelazny AM, Thomas PJ, Stock F, NISC Comparative Sequencing Program Group, Henderson DK, Palmore TN, Segre JA. 2012. Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. Sci Transl Med 4:148–116.
    85.
    Colijn C, Gardy J. 2014. Phylogenetic tree shapes resolve disease transmission patterns. Evol Med Public Health 2014:96–108.
    86.
    Bryant JM, Harris SR, Parkhill J, Dawson R, Diacon AH, van Helden P, Pym A, Mahayiddin AA, Chuchottaworn C, Sanne IM, Louw C, Boeree MJ, Hoelscher M, McHugh TD, Bateson ALC, Hunt RD, Mwaigwisya S, Wright L, Gillespie SH, Bentley SD. 2013. Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study. Lancet Respir Med 1:786–792.
    87.
    Ford CB, Lin PL, Chase MR, Shah RR, Iartchouk O, Galagan J, Mohaideen N, Ioerger TR, Sacchettini JC, Lipsitch M, Flynn JL, Fortune SM. 2011. Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection. Nat Genet 43:482–486.
    88.
    Bryant JM, Schürch AC, van Deutekom H, Harris SR, de Beer JL, de Jager V, Kremer K, van Hijum SA, Siezen RJ, Borgdorff M, Bentley SD, Parkhill J, van Soolingen D. 2013. Inferring patient to patient transmission of Mycobacterium tuberculosis from whole genome sequencing data. BMC Infect Dis 13:110.
    89.
    Pérez-Lago L, Comas I, Navarro Y, González-Candelas F, Herranz M, Bouza E, García-de-Viedma D. 2014. Whole genome sequencing analysis of intrapatient microevolution in Mycobacterium tuberculosis: potential impact on the inference of tuberculosis transmission. J Infect Dis 209:98–108.
    90.
    Rohde K, Yates RM, Purdy GE, Russell DG. 2007. Mycobacterium tuberculosis and the environment within the phagosome. Immunol Rev 219:37–54.
    91.
    O'Garra A, Redford PS, McNab FW, Bloom CI, Wilkinson RJ, Berry MPR. 2013. The immune response in tuberculosis. Annu Rev Immunol 31:475–527.
    92.
    Galagan JE. 2014. Genomic insights into tuberculosis. Nat Rev Genet 15:307–320.
    93.
    Colangeli R, Arcus VL, Cursons RT, Ruthe A, Karalus N, Coley K, Manning SD, Kim S, Marchiano E, Alland D. 2014. Whole genome sequencing of Mycobacterium tuberculosis reveals slow growth and low mutation rates during latent infections in humans. PLoS One 9:e91024.
    94.
    Perdigão J, Silva H, Machado D, Macedo R, Maltez F, Silva C, Jordao L, Couto I, Mallard K, Coll F, Hill-Cawthorne GA, McNerney R, Pain A, Clark TG, Viveiros M, Portugal I. 2014. Unraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon, Portugal, a highly drug resistant setting. BMC Genomics 15:991.
    95.
    Huang Y-S, Chern H-D, Su W-J, Wu J-C, Lai S-L, Yang S-Y, Chang F-Y, Lee S-D. 2002. Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis. Hepatology 35:883–889.
    96.
    Matsumoto T, Ohno M, Azuma J. 2014. Future of pharmacogenetics-based therapy for tuberculosis. Pharmacogenomics 15:601–607.
    97.
    Parkin DP, Vandenplas S, Botha FJ, Vandenplas ML, Seifart HI, van Helden PD, van der Walt BJ, Donald PR, van Jaarsveld PP. 1997. Trimodality of isoniazid elimination: phenotype and genotype in patients with tuberculosis. Am J Respir Crit Care Med 155:1717–1722.
    98.
    Ohno M, Yamaguchi I, Yamamoto I, Fukuda T, Yokota S, Maekura R, Ito M, Yamamoto Y, Ogura T, Maeda K, Komuta K, Igarashi T, Azuma J. 2000. Slow N-acetyltransferase 2 genotype affects the incidence of isoniazid and rifampicin-induced hepatotoxicity. Int J Tuberc Lung Dis 4:256–261.
    99.
    Sharma SK, Balamurugan A, Saha PK, Pandey RM, Mehra NK. 2002. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J Respir Crit Care Med 166:916–919.
    100.
    Haiser HJ, Gootenberg DB, Chatman K, Sirasani G, Balskus EP, Turnbaugh PJ. 2013. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science 341:295–298.
    101.
    Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, Venkatesh M, Jobin C, Yeh L-A, Mani S, Redinbo MR. 2010. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330:831–835.
    102.
    Clayton TA, Baker D, Lindon JC, Everett JR, Nicholson JK. 2009. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc Natl Acad Sci U S A 106:14728–14733.
    103.
    Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung Y-M, Wu Y, Schauer P, Smith JD, Allayee H, Tang WHW, DiDonato JA, Lusis AJ, Hazen SL. 2011. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472:57–63.
    104.
    Azad AK, Sadee W, Schlesinger LS. 2012. Innate immune gene polymorphisms in tuberculosis. Infect Immun 80:3343–3359.
    105.
    Abel L, El-Baghdadi J, Bousfiha AA, Casanova J-L, Schurr E. 2014. Human genetics of tuberculosis: a long and winding road. Philos Trans R Soc Lond B Biol Sci 369:20130428.
    106.
    Shaer O, Nov O. 2014. HCI for personal genomics. Interactions 21:32–37.

    Author Bios

    Marta Wlodarska
    The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
    Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA
    Marta Wlodarska has 6 years of research experience in infectious disease and immunology and is currently a Postdoctoral Fellow at Novartis Institutes for Biomedical Research in Boston, MA. She obtained her B.Sc. with Honors at the University of British Columbia (UBC), Vancouver, Canada. She also completed her Ph.D. at the University of British Columbia, in the laboratory of B. Brett Finlay. Her research focused on discovering immune mechanisms required to maintain intestinal health and their relevance to enteric infection. After completing her Ph.D., she moved to the British Columbia Centre for Disease Control (BCCDC) in Vancouver to gain experience in public health and to understand the transmission dynamics of infectious disease, with a focus on the molecular epidemiology of tuberculosis.
    James C. Johnston
    Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
    James C. Johnston is a Clinical Assistant Professor in the Department of Medicine at UBC and a Michael Smith Foundation Scholar. He received his bachelor's degree from McGill and his M.D. from Queen's University. He returned to McGill for internal medicine training before moving to UBC for his Respiratory Medicine Fellowship. He completed postdoctoral training in tuberculosis research at the BC Centre for Disease Control and has a master's degree in public health from the Harvard School of Public Health. Dr. Johnston joined the BCCDC TB Services as the TB Evaluation Lead in 2010. His interests include TB genomics, TB screening in migrants to countries with low TB incidence, and MDR TB epidemiology and treatment.
    Jennifer L. Gardy
    British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
    School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
    Jennifer L. Gardy is a Senior Scientist at the British Columbia Centre for Disease Control and an Assistant Professor in UBC's School of Population and Public Health. She received a bachelor's degree in cell biology and genetics from UBC in 2000, completed a Ph.D. in computational microbial genomics at Simon Fraser University in 2006, and did 3 years of postdoctoral training in network analysis and systems biology at UBC before joining the BCCDC in 2009. Her research interests are in the use of genomics as a tool for understanding the origins and spread of communicable disease, with a particular emphasis on TB. She is particularly interested in using genomics to reconstruct outbreaks of infectious disease and translating the knowledge gained from genomics studies into real-world public health interventions.
    Patrick Tang [email protected]
    British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    Patrick Tang is a Medical Microbiologist at the British Columbia Centre for Disease Control and a Clinical Associate Professor in Pathology and Laboratory Medicine at the University of British Columbia. He completed his M.D./Ph.D. at UBC, followed by a medical microbiology residency at the University of Toronto. Since 2006, he has led the British Columbia TB/Mycobacteriology Laboratory and the Core Molecular/Genomics Laboratory at the BCCDC. His research interests are in the application of genomics and metagenomics to public health and infectious diseases, as well as the development of new molecular diagnostics. He uses these tools to diagnose outbreaks and unusual clinical diseases at the BCCDC. His other research projects include searching for infectious agents in chronic diseases and outbreaks, using genomics to investigate the dynamics of tuberculosis transmission, studying the microbiomes of people and animals, and even looking for better ways to test for water pollution.

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    Clinical Microbiology Reviews
    Volume 28Number 2April 2015
    Pages: 523 - 539

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    Published online: 25 March 2015

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    Marta Wlodarska
    The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
    Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA
    James C. Johnston
    Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
    Jennifer L. Gardy
    British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
    School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
    Patrick Tang [email protected]
    British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada

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  • Clinical Microbiology ReviewsArticle
    A Structure-Based Classification of Class A β-Lactamases, a Broadly Diverse Family of Enzymes

    A Structure-Based Classification of Class A β-Lactamases, a Broadly Diverse Family of Enzymes

    SUMMARY

    For medical biologists, sequencing has become a commonplace technique to support diagnosis. Rapid changes in this field have led to the generation of large amounts of data, which are not always correctly listed in databases. This is particularly true for data concerning class A β-lactamases, a group of key antibiotic resistance enzymes produced by bacteria. Many genomes have been reported to contain putative β-lactamase genes, which can be compared with representative types. We analyzed several hundred amino acid sequences of class A β-lactamase enzymes for phylogenic relationships, the presence of specific residues, and cluster patterns. A clear distinction was first made between dd-peptidases and class A enzymes based on a small number of residues (S70, K73, P107, 130SDN132, G144, E166, 234K/R, 235T/S, and 236G [Ambler numbering]). Other residues clearly separated two main branches, which we named subclasses A1 and A2. Various clusters were identified on the major branch (subclass A1) on the basis of signature residues associated with catalytic properties (e.g., limited-spectrum β-lactamases, extended-spectrum β-lactamases, and carbapenemases). For subclass A2 enzymes (e.g., CfxA, CIA-1, CME-1, PER-1, and VEB-1), 43 conserved residues were characterized, and several significant insertions were detected. This diversity in the amino acid sequences of β-lactamases must be taken into account to ensure that new enzymes are accurately identified. However, with the exception of PER types, this diversity is poorly represented in existing X-ray crystallographic data.
    ADDENDUM
    A novel plasmid-encoded carbapenemase, named BKC-1, for Brazilian Klebsiella carbapenemase 1, was recently detected among K. pneumoniae clinical isolates (A. G. Nicoletti et al., Antimicrob Agents Chemother 59:5159–5164, 2015, http://dx.doi.org/10.1128/AAC.00158-15). This class A enzyme displays the highest level of identity (63%) to a β-lactamase of Sinorhizobium meliloti. This new class A carbapenemase (subclass A1, cluster RHI, for Rhizobiales) showed some molecular particularities, such as the presence of Cys69 but the absence of Cys238 and the insertion of an Arg residue at position 171 and two residues (Arg and His) at position 241.

    REFERENCES

    1.
    Sawai T, Mitsuhashi S, Yamagishi S. 1968. Drug resistance of enteric bacteria. XIV. Comparison of β-lactamases in gram-negative rod bacteria resistant to a-aminobenzylpenicillin. Jpn J Microbiol 12:423–434.
    2.
    Richmond MH, Sykes RB. 1973. The β-lactamases of gram-negative bacteria and their possible physiological role, p 31–88. In Rose AH, Tempest DW (ed), Advances in microbial physiology, vol 9. Academic Press, New York, NY.
    3.
    Medeiros AA. 1997. Evolution and dissemination of β-lactamases accelerated by generations of β-lactam antibiotics. Clin Infect Dis 24(Suppl 1):S19–S45.
    4.
    Bush K, Jacoby GA, Medeiros AA. 1995. A functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 39:1211–1133.
    5.
    Bush K, Jacoby GA. 2010. Updated functional classification of β-lactamases. Antimicrob Agents Chemother 54:969–976.
    6.
    Ambler RP. 1980. The structure of β-lactamases. Philos Trans R Soc Lond B Biol Sci 289:321–331.
    7.
    Galleni M, Lamotte-Brasseur J, Rossolini GM, Spencer J, Dideberg O, Frère JM. 2001. Standard numbering scheme for class B β-lactamases. Antimicrob Agents Chemother 45:660–663.
    8.
    Bush K, Fisher JF. 2011. Epidemiological expansion, structural studies, and clinical challenges of new β-lactamases from gram-negative bacteria. Annu Rev Microbiol 65:455–478.
    9.
    Buchan BW, Ledeboer NA. 2014. Emerging technologies for the clinical microbiology laboratory. Clin Microbiol Rev 27:783–822.
    10.
    Hall BG, Barlow M. 2004. Evolution of the serine β-lactamases: past, present and future. Drug Resist Updat 7:111–123.
    11.
    Urbach C, Fastrez J, Soumillion P. 2008. A new family of cyanobacterial penicillin-binding proteins. A missing link in the evolution of class A β-lactamases. J Biol Chem 283:32516–32526.
    12.
    Matagne A, Lamotte-Brasseur J, Frère JM. 1998. Catalytic properties of class A β-lactamases: efficiency and diversity. Biochem J 330:581–598.
    13.
    Bush K. 2013. The ABCD's of β-lactamase nomenclature. J Infect Chemother 19:549–559.
    14.
    Galán JC, Reig M, Navas A, Baquero F, Blazquez J. 2000. ACI-1 from Acidaminococcus fermentans: characterization of the first β-lactamase in anaerobic cocci. Antimicrob Agents Chemother 44:3144–3149.
    15.
    Weng SF, Chao YF, Lin JW. 2004. Identification and characteristic analysis of the ampC gene encoding β-lactamase from Vibrio fischeri. Biochem Biophys Res Commun 314:838–843.
    16.
    Poirel L, Laurent F, Naas T, Labia R, Boiron P, Nordmann P. 2001. Molecular and biochemical analysis of AST-1, a class A β-lactamase from Nocardia asteroides sensu stricto. Antimicrob Agents Chemother 45:878–882.
    17.
    Girlich D, Leclercq R, Naas T, Nordmann P. 2007. Molecular and biochemical characterization of the chromosome-encoded class A β-lactamase BCL-1 from Bacillus clausii. Antimicrob Agents Chemother 51:4009–4014.
    18.
    Poirel L, Brinas L, Verlinde A, Ide L, Nordmann P. 2005. BEL-1, a novel clavulanic acid-inhibited extended-spectrum β-lactamase, and the class 1 integron In120 in Pseudomonas aeruginosa. Antimicrob Agents Chemother 49:3743–3748.
    19.
    Glupczynski Y, Bogaerts P, Deplano A, Berhin C, Huang TD, Van Eldere J, Rodriguez-Villalobos HJ. 2010. Detection and characterization of class A extended-spectrum-β-lactamase-producing Pseudomonas aeruginosa isolates in Belgian hospitals. Antimicrob Agents Chemother 65:866–871.
    20.
    Bonnet R, Sampaio JLM, Chanal C, Sirot D, de Champs C, Viallard JL, Labia R, Sirot J. 2000. A novel class A extended-spectrum β-lactamase (BES-1) in Serratia marcescens isolated in Brazil. Antimicrob Agents Chemother 44:3061–3068.
    21.
    Girlich D, Poirel L, Nordmann P. 2010. Novel ambler class A carbapenem-hydrolyzing β-lactamase from a Pseudomonas fluorescens isolate from the Seine River, Paris, France. Antimicrob Agents Chemother 54:328–332.
    22.
    Hackbarth CJ, Unsal I, Chambers HF. 1997. Cloning and sequence analysis of a class A β-lactamase from Mycobacterium tuberculosis H37Ra. Antimicrob Agents Chemother 41:1182–1185.
    23.
    Wang F, Cassidy C, Sacchettini JC. 2006. Crystal structure and activity studies of the Mycobacterium tuberculosis β-lactamase reveal its critical role in resistance to β-lactam antibiotics. Antimicrob Agents Chemother 50:2762–2771.
    24.
    Lartigue MF, Poirel L, Fortineau N, Nordmann P. 2005. Chromosome-borne class A BOR-1 β-lactamase of Bordetella bronchiseptica and Bordetella parapertussis. Antimicrob Agents Chemother 49:2565–2567.
    25.
    Cheung TK, Ho PL, Woo PC, Yuen KY, Chau PY. 2002. Cloning and expression of class A β-lactamase gene blaA(BPS) in Burkholderia pseudomallei. Antimicrob Agents Chemother 46:1132–1135.
    26.
    Yi H, Cho KH, Cho YS, Kim K, Nierman WC, Kim HS. 2012. Twelve positions in a β-lactamase that can expand its substrate spectrum with a single amino acid substitution. PLoS One 7:e37585.
    27.
    Yi H, Kim K, Cho KH, Jung O, Kim HS. 2012. Substrate spectrum extension of PenA in Burkholderia thailandensis with a single amino acid deletion, Glu168del. Antimicrob Agents Chemother 56:4005–4008.
    28.
    Meziane-Cherif D, Decré D, Høiby EA, Courvalin P, Périchon B. 2008. Genetic and biochemical characterization of CAD-1, a chromosomally encoded new class A penicillinase from Carnobacterium divergens. Antimicrob Agents Chemother 52:551–556.
    29.
    Bellais S, Naas T, Nordmann P. 2002. Molecular and biochemical characterization of Ambler class A extended-spectrum β-lactamase CGA-1 from Chryseobacterium gleum. Antimicrob Agents Chemother 46:966–970.
    30.
    Matsumoto T, Nagata M, Ishimine N, Kawasaki K, Yamauchi K, Hidaka E, Kasuga E, Horiuchi K, Oana K, Kawakami Y, Honda T. 2012. Characterization of CIA-1, an Ambler class A extended-spectrum β-lactamase from Chryseobacterium indologenes. Antimicrob Agents Chemother 56:588–590.
    31.
    Petrella S, Renard M, Ziental-Gelus N, Clermont D, Jarlier V, Sougakoff W. 2006. Characterization of the chromosomal class A β-lactamase CKO from Citrobacter koseri. FEMS Microbiol Lett 254:285–292.
    32.
    Rossolini GM, Franceschini N, Caravelli B, Riccio ML, Galleni M, Frère JM, Amicosante G. 1999. Cloning of a Chryseobacterium (Flavobacterium) meningosepticum chromosomal gene (blaACME) encoding an extended-spectrum class A β-lactamase related to the Bacteroides cephalosporinases and the VEB-1 and PER β-lactamases. Antimicrob Agents Chemother 43:2193–2199.
    33.
    Guillon H, Eb F, Mammeri H. 2010. Characterization of CSP-1, a novel extended-spectrum β-lactamase produced by a clinical isolate of Capnocytophaga sputigena. Antimicrob Agents Chemother 54:2231–2234.
    34.
    Bauernfeind A, Stemplinger I, Jungwirth R, Casellas JM. 1996. Sequences of β-lactamase genes encoding CTX-M-1 (MEN-1) and CTX-M-2 and relationship of their amino acid sequences with those of other β-lactamases. Antimicrob Agents Chemother 40:509–513.
    35.
    Bonnet R, Sampaio JLM, Labia R, de Champs C, Sirot D, Chanal C, Sirot J. 2000. A novel CTX-M β-lactamase (CTX-M-8) in cefotaxime-resistant Enterobacteriaceae isolated in Brazil. Antimicrob Agents Chemother 44:1936–1942.
    36.
    Morin AS, Poirel L, Mory F, Labia R, Nordmann P. 2002. Biochemical-genetic analysis and distribution of DES-1, an Ambler class A extended-spectrum β-lactamase from Desulfovibrio desulfuricans. Antimicrob Agents Chemother 46:3215–3222.
    37.
    Vimont S, Poirel L, Naas T, Nordmann P. 2002. Identification of a chromosome-borne expanded-spectrum class A β-lactamase from Erwinia persicina. Antimicrob Agents Chemother 46:3401–3405.
    38.
    Laurent F, Poirel L, Naas T, Chaibi EB, Labia R, Boiron P, Nordmann P. 1999. Biochemical-genetic analysis and distribution of FAR-1, a class A β-lactamase from Nocardia farcinica. Antimicrob Agents Chemother 43:1644–1650.
    39.
    Péduzzi J, Farzaneh S, Reynaud A, Barthélémy M, Labia R. 1997. Characterization and amino acid sequence analysis of a new oxyimino cephalosporin-hydrolyzing class A β-lactamase from Serratia fonticola CUV. Biochim Biophys Acta 1341:58–70.
    40.
    Toth M, Vakulenko V, Antunes NT, Frase H, Vakulenko SB. 2012. Class A carbapenemase FPH-1 from Francisella philomiragia. Antimicrob Agents Chemother 56:2852–2857.
    41.
    Antunes NT, Frase H, Toth M, Vakulenko SB. 2012. The class A β-lactamase FTU-1 is native to Francisella tularensis. Antimicrob Agents Chemother 56:666–671.
    42.
    Poirel L, Le Thomas I, Naas T, Karim A, Nordmann P. 2000. Biochemical sequence analyses of GES-1, a novel class A extended-spectrum β-lactamase, and the class 1 integron In52 from Klebsiella pneumoniae. Antimicrob Agents Chemother 44:622–632.
    43.
    Naas T, Aubert D, Ozcan A, Nordmann P. 2007. Chromosome-encoded narrow-spectrum Ambler class A β-lactamase GIL-1 from Citrobacter gillenii. Antimicrob Agents Chemother 51:1365–1372.
    44.
    Beauchef-Havard A, Arlet G, Gautier V, Labia R, Grimont P, Philippon A. 2003. Molecular and biochemical characterization of a novel class A β-lactamase (HER-1) from Escherichia hermannii. Antimicrob Agents Chemother 47:2669–2673.
    45.
    Liassine N, Madec S, Ninet B, Metral C, Fouchereau-Péron M, Labia R, Auckenthaler R. 2002. Postneurosurgical meningitis due to Proteus penneri with selection of a ceftriaxone-resistant isolate: analysis of chromosomal class A β-lactamase HugA and its LysR-type regulatory protein HugR. Antimicrob Agents Chemother 46:216–219.
    46.
    Giakkoupi P, Tzouvelekis LS, Tsakris A, Loukova V, Sofianou D, Tzelepi E. 2000. IBC-1, a novel integron-associated class A β-lactamase with extended-spectrum properties produced by an Enterobacter cloacae clinical strain. Antimicrob Agents Chemother 44:2247–2253.
    47.
    Rasmussen BA, Bush K, Keeney D, Yang Y, Hare R, O'Gara C, Medeiros AA. 1996. Characterization of IMI-1 β-lactamase, a class A carbapenem-hydrolyzing enzyme from Enterobacter cloacae. Antimicrob Agents Chemother 40:2080–2086.
    48.
    Humeniuk C, Arlet G, Gautier V, Grimont P, Labia R, Philippon A. 2002. β-Lactamases of Kluyvera ascorbata, probable progenitors of some plasmid-encoded CTX-M types. Antimicrob Agents Chemother 46:3045–3049.
    49.
    Decousser JW, Poirel L, Nordmann P. 2001. Characterization of a chromosomally encoded extended-spectrum class A β-lactamase from Kluyvera cryocrescens. Antimicrob Agents Chemother 45:3595–3598.
    50.
    Poirel L, Kämpfer P, Nordmann P. 2002. Chromosome-encoded Ambler class A β-lactamase of Kluyvera georgiana, a probable progenitor of a subgroup of CTX-M extended-spectrum β-lactamases. Antimicrob Agents Chemother 46:4038–4040.
    51.
    Smith Moland E, Hanson ND, Herrera VL, Black JA, Lockhart TJ, Hossain A, Johnson JA, Goering RV, Thomson KS. 2003. Plasmid-mediated, carbapenem-hydrolysing β-lactamase, KPC-2, in Klebsiella pneumoniae isolates. J Antimicrob Chemother 51:711–714.
    52.
    Poirel L, Cattoir V, Soares A, Soussy CJ, Nordmann P. 2007. Novel Ambler class A β-lactamase LAP-1 and its association with the plasmid-mediated quinolone resistance determinant QnrS1. Antimicrob Agents Chemother 51:631–637.
    53.
    Doublet B, Robin F, Casin I, Fabre L, Le Flèche A, Bonnet R, Weill FX. 2010. Molecular and biochemical characterization of the natural chromosome-encoded class A β-lactamase from Pseudomonas luteola. Antimicrob Agents Chemother 54:45–51.
    54.
    Soroka D, Dubée V, Soulier-Escrihuela O, Cuinet G, Hugonnet JE, Gutmann L, Mainardi JL, Arthur M. 2014. Characterization of broad-spectrum Mycobacterium abscessus class A β-lactamase. J Antimicrob Chemother 69:691–696.
    55.
    Bercot B, Nordmann P, Drancourt M, Poirel L. 2012. Chromosome-encoded extended-spectrum class A β-lactamase MIN-1 from Minibacterium massiliensis. Antimicrob Agents Chemother 56:4009–4012.
    56.
    Tanaka M, Okuyama H, Morita N. 2001. Characterization of the gene encoding the β-lactamase of the psychrophilic marine bacterium Moritella marina strain MP-1. Biosci Biotechnol Biochem 65:666–669.
    57.
    Mariotte-Boyer S, Nicolas-Chanoine MH, Labia R. 1996. A kinetic study of NMC-A β-lactamase, an Ambler class A carbapenemase also hydrolyzing cephamycins. FEMS Microbiol Lett 143:29–33.
    58.
    Fèvre C, Passet V, Weill FX, Grimont PAD, Brisse S. 2005. Variants of the Klebsiella pneumoniae OKP chromosomal β-lactamase are divided into two main groups, OKP-A and OKP-B. Antimicrob Agents Chemother 49:5149–5152.
    59.
    Walckenaer E, Poirel L, Leflon-Guibout V, Nordmann P, Nicolas-Chanoine MH. 2004. Genetic and biochemical characterization of the chromosomal class A β-lactamases of Raoultella (formerly Klebsiella) planticola and Raoultella ornithinolytica. Antimicrob Agents Chemother 48:305–312.
    60.
    Fournier B, Roy PH, Lagrange PH, Philippon A. 1996. Chromosomal β-lactamase genes of Klebsiella oxytoca are divided into two main groups, blaOXY-1 and blaOXY-2. Antimicrob Agents Chemother 40:454–459.
    61.
    Poirel L, Rodriguez-Martinez JM, Plésiat P, Nordmann P. 2009. Naturally occurring class A β-lactamases from the Burkholderia cepacia complex. Antimicrob Agents Chemother 53:876–882.
    62.
    Trépanier S, Prince A, Huletsky A. 1997. Characterization of the penA and penR genes of Burkholderia cepacia 249 which encode the chromosomal class A penicillinase and its LysR-type transcriptional regulator. Antimicrob Agents Chemother 41:2399–2405.
    63.
    Papp-Wallace KM, Taracila MA, Gatta JA, Ohuchi N, Bonomo RA, Nukaga M. 2013. Insights into β-lactamases from Burkholderia species, two phylogenetically related yet distinct resistance determinants. J Biol Chem 288:19090–19102.
    64.
    Tian GB, Adams-Haduch JM, Bogdanovich T, Wang HN, Doi Y. 2011. PME-1, an extended-spectrum β-lactamase identified in Pseudomonas aeruginosa. Antimicrob Agents Chemother 55:2710–2713.
    65.
    Bellais S, Rholl L, Fortineau N, Decousser JW, Nordmann P. 2001. Biochemical-genetic characterization of the chromosomally encoded extended-spectrum class A β-lactamase from Rahnella aquatilis. Antimicrob Agents Chemother 45:2965–2968.
    66.
    Choury D, Szajnert MF, Joly-Guillou ML, Azibi K, Delpech M, Paul G. 2000. Nucleotide sequence of the bla(RTG-2)(CARB-5) gene and phylogeny of a new group of carbenicillinases. Antimicrob Agents Chemother 44:1070–1074.
    67.
    Poirel L, Corvec S, Rapoport M, Mugnier P, Petroni A, Pasteran F, Faccone D, Galas M, Drugeon H, Cattoir V, Nordmann P. 2007. Identification of the novel narrow-spectrum β-lactamase SCO-1 in Acinetobacter spp. from Argentina. Antimicrob Agents Chemother 51:2179–2184.
    68.
    Papagiannitsis CC, Loli A, Tzouvelekis LS, Tzelepi E, Arlet G, Miriagou V. 2007. SCO-1, a novel plasmid-mediated class A β-lactamase with carbenicillinase characteristics from Escherichia coli. Antimicrob Agents Chemother 51:2185–2188.
    69.
    Petrella S, Clermont D, Casin I, Jarlier V, Sougakoff W. 2001. Novel class A β-lactamase Sed-1 from Citrobacter sedlakii: genetic diversity of β-lactamases within the Citrobacter genus. Antimicrob Agents Chemother 45:2287–2298.
    70.
    Henriques I, Moura A, Alves A, Saavedra MJ, Correia A. 2004. Molecular characterization of a carbapenem-hydrolyzing class A β-lactamase, SFC-1, from Serratia fonticola UTAD54. Antimicrob Agents Chemother 48:2321–2324.
    71.
    Matsumoto Y, Inoue M. 1999. Characterization of SFO-1, a plasmid-mediated inducible class A β-lactamase from Enterobacter cloacae. Antimicrob Agents Chemother 43:307–313.
    72.
    Lamoureaux TL, Vakulenko V, Toth M, Frase H, Vakulenko SB. 2013. A novel extended-spectrum β-lactamase, SGM-1, from an environmental isolate of Sphingobium sp. Antimicrob Agents Chemother 57:3783–3788.
    73.
    Lartigue MF, Nordmann P, Edelstein MV, Cuzon G, Brisse S, Poirel L. 2013. Characterization of an extended-spectrum class A β-lactamase from a novel enterobacterial species taxonomically related to Rahnella spp/Ewingella spp. J Antimicrob Chemother 68:1733–1736.
    74.
    Queenan AM, Torres-Viera C, Gold HS, Carmeli Y, Eliopoulos GM, Moellering RC, Jr, Quinn JP, Hindler J, Medeiros AA, Bush K. 2000. SME-type carbapenem-hydrolyzing class A β-lactamases from geographically diverse Serratia marcescens strains. Antimicrob Agents Chemother 44:3035–3039.
    75.
    Handal T, Giraud-Morin C, Caugant DA, Madinier I, Olsen I, Fosse T. 2005. Chromosome- and plasmid-encoded β-lactamases in Capnocytophaga spp. Antimicrob Agents Chemother 49:3940–3943.
    76.
    Ehrmann E, Handal T, Tamanai-Shacoori Z, Bonnaure-Mallet M, Fosse T. 2014. High prevalence of β-lactam and macrolide resistance genes in human oral Capnocytophaga species. J Antimicrob Chemother 69:381–384.
    77.
    Ogawara H, Horikawa S, Shimada-Miyoshi S, Yasuzawa K. 1978. Production and property of β-lactamases in Streptomyces: comparison of the strains isolated newly and thirty years ago. Antimicrob Agents Chemother 13:865–870.
    78.
    Sendouda A, Urabe H, Ogawara H. 1993. Cloning, nucleotide sequence and expression of a β-lactamase gene from Streptomyces lavendulae. FEMS Microbiol Lett 112:343–348.
    79.
    Walckenaer E, Delmas J, Leflon-Guibout V, Bonnet R, Nicolas-Chanoine MH. 16 June 2015. Genetic, biochemical characterization and mutagenesis of the chromosomal class A β-lactamase of Raoultella (formerly Klebsiella) terrigena. Pathol Biol (Paris) doi:
    80.
    Silva J, Aguilar C, Ayala G, Estrada MA, Garza-Ramos U, Lara-Lemus R, Ledezma L. 2000. TLA-1: a new plasmid mediated extended-spectrum β-lactamase from Escherichia coli. Antimicrob Agents Chemother 44:997–1003.
    81.
    Girlich D, Poirel L, Schluter A, Nordmann P. 2005. TLA-2, a novel Ambler class A expanded-spectrum β-lactamase. Antimicrob Agents Chemother 49:4767–4770.
    82.
    Ishii Y, Ohno A, Taguchi H, Imajo S, Ishiguro M, Matsuzaw H. 1995. Cloning and sequence of the gene encoding a cefotaxime-hydrolyzing class A β-lactamase isolated from Escherichia coli. Antimicrob Agents Chemother 39:2269–2275.
    83.
    Jun LJ, Kim JH, Jin JW, Jeong HD. 2012. Characterization of a new β-lactamase gene from isolates of Vibrio spp. in Korea. J Microbiol Biotechnol 22:555–562.
    84.
    Poirel L, Naas T, Guibert M, Chaibi EB, Labia R, Nordmann P. 1999. Molecular and biochemical characterization of VEB-1, a novel class A extended-spectrum β-lactamase encoded by an Escherichia coli integron gene. Antimicrob Agents Chemother 43:573–581.
    85.
    Teo JW, Suwanto A, Poh CL. 2000. Novel β-lactamase genes from two environmental isolates of Vibrio harveyi. Antimicrob Agents Chemother 44:1309–1314.
    86.
    Weng SF, Chen CY, Lee YS, Lin JW, Tseng YH. 1999. Identification of a novel β-lactamase produced by Xanthomonas campestris, a phytopathogenic bacterium. Antimicrob Agents Chemother 43:1792–1797.
    87.
    Sharma S, Mittal S, Mallik S, Virdi JS. 2006. Molecular characterization of β-lactamase genes blaA and blaB of Yersinia enterocolitica biovar 1A. FEMS Microbiol Lett 257:319–327.
    88.
    Dortet L, Poirel L, Abbas S, Oueslati S, Nordmann P. 21 September 2015. Genetic and biochemical characterization of FRI-1, a carbapenem-hydrolyzing class A β-lactamase from Enterobacter cloacae. Antimicrob Agents Chemother.
    89.
    Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG. 1997. The ClustalX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876–4882.
    90.
    Saitou N, Nei M. 1987. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425.
    91.
    Maddison DR, Swofford DJ, Maddison WP. 1997. NEXUS: an extensible file format for systematic information. Syst Biol 46:590–621.
    92.
    Walther-Rasmussen J, Høiby N. 2007. Class A carbapenemases. J Antimicrob Chemother 60:470–482.
    93.
    Galán JC. 2002. Trans-gram gene transfer: the case of β-lactamases. Rev Esp Quimioter 15:215–223. (In Spanish.)
    94.
    Brown JR, Douady CJ, Italia MJ, Marshall WE, Stanhope MJ. 2001. Universal trees based on large combined protein sequence data sets. Nat Genet 28:281–285.
    95.
    Naas T, Poirel L, Nordmann P. 2008. Minor extended-spectrum β-lactamases. Clin Microbiol Infect 14(Suppl 1):42–52.
    96.
    Ambler RP, Coulson AF, Frère JM, Ghuysen JM, Joris B, Forsman M, Levesque RC, Tiraby G, Waley SG. 1991. A standard numbering scheme for the class A β-lactamases. Biochem J 276:269–270.
    97.
    Risso VA, Gavira JA, Mejia-Carmona DF, Gaucher EA, Sanchez-Ruiz JM. 2013. Hyperstability and substrate promiscuity in laboratory resurrections of Precambrian β-lactamases. J Am Chem Soc 135:2899–2902.
    98.
    Tranier S, Bouthors AT, Maveyraud L, Guillet V, Sougakoff W, Samama JP. 2000. The high resolution crystal structure for class A β-lactamase PER-1 reveals the bases for its increase in breadth of activity. J Biol Chem 275:28075–28082.
    99.
    Ruggiero M, Kerff F, Herman R, Sapunaric F, Galleni M, Gutkind G, Charlier P, Sauvage E, Power P. 2014. Crystal structure of the extended-spectrum β-lactamase PER-2 and insights into the role of specific residues in the interaction with β-lactams and β-lactamase inhibitors. Antimicrob Agents Chemother 58:5994–6002.
    100.
    Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ, Jr. 2006. Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clin Microbiol Rev 19:259–282.
    101.
    Chen Y, Tenover FC, Koehler TM. 2004. β-Lactamase gene expression in a penicillin-resistant Bacillus anthracis strain. Antimicrob Agents Chemother 48:4873–4877.
    102.
    David MZ, Daum RS. 2010. Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev 23:616–687.
    103.
    Kapadia M, Rolston KV, Han XY. 2007. Invasive Streptomyces infections: six cases and literature review. Am J Clin Pathol 127:619–624.
    104.
    Kurai S, Urabe H, Ogawara H. 1995. Cloning, sequencing, and site-directed mutagenesis of β-lactamase gene from Streptomyces fradiae Y59. Antimicrob Agents Chemother 39:260–263.
    105.
    Loncaric I, Hübber-Heiss A, Posautz A, Stalder GL, Hoffmann D, Rosengarten R, Walzer C. 2013. Characterization of methicillin-resistant Staphylococcus spp. carrying the mecC gene, isolated from wildlife. J Antimicrob Chemother 68:2222–2225.
    106.
    Materon IC, Queenan AM, Koehler TM, Bush K, Palzkill T. 2003. Biochemical characterization of β-lactamases Bla1 and Bla2 from Bacillus anthracis. Antimicrob Agents Chemother 47:2040–2042.
    107.
    Pérez-Llarena F, Martin JF, Galleni M, Coque JJ, Fuente JL, Frère JM, Liras P. 1997. The bla gene of the cephamycin cluster of Streptomyces clavuligerus encodes a class A β-lactamase of low enzymatic activity. J Bacteriol 179:6035–6040.
    108.
    Seipke RF, Kaltenpoth M, Hutchings MI. 2012. Streptomyces as symbionts: an emerging and widespread theme? FEMS Microbiol Rev 36:862–876.
    109.
    Chambers HF, Moreau D, Yajko D, Miick C, Wagner C, Hackbarth C, Kocagoz S, Rosenberg E, Hadley WK, Nikaido H. 1995. Can penicillins and other β-lactam antibiotics be used to treat tuberculosis? Antimicrob Agents Chemother 39:2620–2624.
    110.
    Kurz SG, Bonomo RA. 2012. Reappraising the use of β-lactams to treat tuberculosis. Expert Rev Anti Infect Ther 10:999–1006.
    111.
    Quinting B, Reyrat JM, Monnaie D, Amicosante G, Pelicic V, Gicquel B, Frère JM, Galleni M. 1997. Contribution of β-lactamase production to the resistance of mycobacteria to β-lactam antibiotics. FEBS Lett 406:275–278.
    112.
    Utrup LJ, Moore TD, Actor P, Poupard JA. 1995. Susceptibilities of nontuberculosis mycobacterial species to amoxicillin-clavulanic acid alone and in combination with antimycobacterial agents. Antimicrob Agents Chemother 39:1454–1457.
    113.
    Sauvage E, Fonzé E, Quinting B, Galleni M, Frère JM, Charlier P. 2006. Crystal structure of the Mycobacterium fortuitum class A β-lactamase: structural basis for broad substrate specificity. Antimicrob Agents Chemother 50:2516–2521.
    114.
    Gniadkowski M. 2008. Evolution of extended-spectrum β-lactamases by mutation. Clin Microbiol Infect 14(Suppl 1):11–32.
    115.
    Page MG. 2008. Extended-spectrum β-lactamases: structure and kinetic mechanism. Clin Microbiol Infect 14(Suppl 1):63–74.
    116.
    Philippon A, Arlet G. 2012. Entérobactéries et bêta-lactamines: phénotypes de résistance naturelle. Pathol Biol (Paris) 60:112–126.
    117.
    Mulvey MR, Boyd DA, Olson AB, Doublet B, Cloeckaert A. 2006. The genetics of Salmonella genomic island 1. Microbes Infect 8:1915–1922.
    118.
    Vanhove M, Guillaume G, Ledent P, Richards JH, Pain RH, Frère JM. 1997. Kinetic and thermodynamic consequences of the removal of the Cys-77-Cys-123 disulphide bond for the folding of TEM-1 β-lactamase. Biochem J 321:413–417.
    119.
    Lim D, Sanschagrin F, Passmore L, De Castro L, Levesque RC, Strynadka NC. 2001. Insights into the molecular basis for the carbenicillinase activity of PSE-4 β-lactamase from crystallographic and kinetic studies. Biochemistry 40:395–402.
    120.
    Lenfant F, Petit A, Labia R, Maveyraud L, Samama JP, Masson JM. 1993. Site-directed mutagenesis of β-lactamase TEM-1. Investigating the potential role of specific residues on the activity of Pseudomonas-specific enzymes. Eur J Biochem 217:939–946.
    121.
    Degnan PH, Yu Y, Sisneros N, Wing RA, Moran NA. 2009. Hamiltonella defensa, genome evolution of protective bacterial endosymbiont from pathogenic ancestors. Proc Natl Acad Sci U S A 106:9063–9068.
    122.
    Rao Q, Wang S, Su YL, Bing XL, Liu SS, Wang XW. 2012. Draft genome sequence of “Candidatus Hamiltonella defensa,” an endosymbiont of the whitefly Bemisia tabaci. J Bacteriol 194:3558.
    123.
    Potron A, Poirel L, Croizé J, Chanteperdrix V, Nordmann P. 2009. Genetic and biochemical characterization of the first extended-spectrum CARB-type β-lactamase, RTG-4, from Acinetobacter baumannii. Antimicrob Agents Chemother 53:3010–3016.
    124.
    Bonnet R. 2004. Growing group of extended-spectrum β-lactamases: the CTX-M enzymes. Antimicrob Agents Chemother 48:1–14.
    125.
    Zhao WH, Hu ZQ. 2013. Epidemiology and genetics of CTX-M extended-spectrum β-lactamases in Gram-negative bacteria. Crit Rev Microbiol 39:79–101.
    126.
    Fernández A, Pereira MJ, Suárez JM, Poza M, Treviño M, Villalón P, Sáez-Nieto JA, Regueiro BJ, Villanueva R, Bou G. 2011. Emergence in Spain of a multidrug-resistant Enterobacter cloacae clinical isolate producing SFO-1 extended-spectrum β-lactamase. J Clin Microbiol 49:822–828.
    127.
    González-López JJ, Coelho A, Larrosa MN, Lavilla S, Bartolomé R, Prats G. 2009. First detection of plasmid-encoded blaOXY β-lactamase. Antimicrob Agents Chemother 53:3143–3146.
    128.
    Fournier B, Arlet G, Lagrange PH, Philippon A. 1994. Klebsiella oxytoca: resistance to aztreonam by overproduction of the chromosomally encoded β-lactamase. FEMS Microbiol Lett 116:31–36.
    129.
    Fournier B, Lagrange PH, Philippon A. 1996. In-vitro susceptibility of Klebsiella oxytoca strains to 13 β-lactams in the presence and absence of β-lactamase inhibitors. J Antimicrob Chemother 37:931–942.
    130.
    Péduzzi J, Reynaud A, Baron P, Barthélémy M, Labia R. 1994. Chromosomally encoded cephalosporin-hydrolyzing β-lactamase of Proteus vulgaris RO104 belongs to Ambler's class A. Biochim Biophys Acta 1207:31–39.
    131.
    Ruimy R, Meziane-Cherif D, Momcilovic S, Arlet G, Andremont A, Courvalin P. 2010. RAHN-2, a chromosomal extended-spectrum class A β-lactamase from Rahnella aquatilis. J Antimicrob Chemother 65:1619–1623.
    132.
    Delmas J, Chen Y, Prati F, Robin F, Shoichet BK, Bonnet R. 2008. Structure and dynamics of CTX-M enzymes reveal insights into substrate accommodation by extended-spectrum β-lactamases. J Mol Biol 375:192–201.
    133.
    Delmas J, Robin F, Carvalho F, Mongaret C, Bonnet R. 2006. Prediction of the evolution of ceftazidime resistance in extended-spectrum β-lactamase CTX-M-9. Antimicrob Agents Chemother 50:731–738.
    134.
    Shimizu-Ibuka A, Oishi M, Yamada S, Ishii Y, Mura K, Sakai H, Matsuzawa H. 2011. Roles of residues Cys69, Asn104, Phe160, Gly232, Ser237, and Asp240 in extended-spectrum β-lactamase Toho-1. Antimicrob Agents Chemother 55:284–290.
    135.
    Decré D, Burghoffer B, Gautier V, Petit JC, Arlet G. 2004. Outbreak of multi-resistant Klebsiella oxytoca involving strains with extended-spectrum β-lactamases and strains with extended-spectrum activity of the chromosomal β-lactamase. J Antimicrob Chemother 54:881–888.
    136.
    Cantón R, Morosini MI, de la Maza OM, de la Pedrosa EG. 2008. IRT and CMT β-lactamases and inhibitor resistance. Clin Microbiol Infect 14(Suppl 1):53–62.
    137.
    Celenza G, Luzi C, Aschi M, Segatore B, Setacci D, Pellegrini C, Forcella C, Amicosante G, Perilli M. 2008. Natural D240G Toho-1 mutant conferring resistance to ceftazidime: biochemical characterization of CTX-M-43. J Antimicrob Chemother 62:991–997.
    138.
    Mammeri H, Poirel L, Nordmann P. 2003. In vivo selection of a chromosomally encoded β-lactamase variant conferring ceftazidime resistance in Klebsiella oxytoca. Antimicrob Agents Chemother 47:3739–3742.
    139.
    Younes A, Hamouda A, Amyes SG. 2011. First report of a novel extended-spectrum β-lactamase KOXY-2 producing Klebsiella oxytoca that hydrolyses cefotaxime and ceftazidime. J Chemother 23:127–130.
    140.
    Ripoll A, Baquero F, Novais A, Rodríguez-Domínguez MJ, Turrientes MC, Cantón R, Galán JC. 2011. In vitro selection of variants resistant to β-lactams plus β-lactamase inhibitors in CTX-M β-lactamases: predicting the in vivo scenario? Antimicrob Agents Chemother 55:4530–4536.
    141.
    Sirot D, Labia R, Pouedras P, Chanal-Claris C, Cerceau C, Sirot J. 1998. Inhibitor-resistant OXY-2-derived β-lactamase produced by Klebsiella oxytoca. Antimicrob Agents Chemother 42:2184–2187.
    142.
    Hornstein MJ, Jupeau AM, Scavizzi MR, Philippon AM, Grimont PAD. 1985. In vitro susceptibilities of 126 clinical isolates of Yersinia enterocolitica to 21 β-lactam antibiotics. Antimicrob Agents Chemother 27:806–811.
    143.
    Pham JN, Bell SM, Martin L, Carniel E. 2000. The β-lactamases and β-lactam antibiotic susceptibility of Yersinia enterocolitica. J Antimicrob Chemother 46:951–957.
    144.
    Stock I, Wiedemann B. 1999. An in-vitro study of the antimicrobial susceptibilities of Yersinia enterocolitica and the definition of a database. J Antimicrob Chemother 43:37–45.
    145.
    Poirel L, Pitout JD, Nordmann P. 2007. Carbapenemases: molecular diversity and clinical consequences. Future Microbiol 2:501–512.
    146.
    Queenan AM, Bush K. 2007. Carbapenemases: the versatile β-lactamases. Clin Microbiol Rev 20:440–458.
    147.
    Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. 2011. Carbapenems: past, present, and future. Antimicrob Agents Chemother 55:4943–4960.
    148.
    Papp-Wallace KM, Bethel CR, Distler AM, Kasuboski C, Taracila M, Bonomo RA. 2010. Inhibitor resistance in the KPC-2 β-lactamase, a preeminent property of this class A β-lactamase. Antimicrob Agents Chemother 54:890–897.
    149.
    Ke W, Bethel CR, Papp-Wallace KM, Pagadala SR, Nottingham M, Fernandez D, Buynak JD, Bonomo RA, van den Akker F. 2012. Crystal structures of KPC-2 β-lactamase in complex with 3-nitrophenyl boronic acid and the penam sulfone PSR-3-226. Antimicrob Agents Chemother 56:2713–2718.
    150.
    Sougakoff W, L'Hermite G, Pernot L, Naas T, Guillet V, Nordmann P, Jarlier V, Delettré J. 2002. Structure of the imipenem-hydrolyzing class A β-lactamase SME-1 from Serratia marcescens. Acta Crystallogr D Biol Crystallogr 58:267–274.
    151.
    Fonseca F, Chudyk EI, van der Kamp MW, Correia A, Mulholland AJ, Spencer J. 2012. The basis for carbapenem hydrolysis by class A β-lactamases: a combined investigation using crystallography and simulations. J Am Chem Soc 134:18275–18285.
    152.
    Papp-Wallace KM, Taracila MA, Smith KM, Xu Y, Bonomo RA. 2012. Understanding the molecular determinants of substrate and inhibitor specificities in the carbapenemase KPC-2: exploring the roles of Arg220 and Glu276. Antimicrob Agents Chemother 56:4428–4438.
    153.
    Poirel L, Brinas L, Fortineau N, Nordmann P. 2005. Integron-encoded GES-type extended-spectrum β-lactamase with increased activity toward aztreonam in Pseudomonas aeruginosa. Antimicrob Agents Chemother 49:3593–3597.
    154.
    Delbrück H, Bogaerts P, Kupper MB, Rezende de Castro R, Bennink S, Glupczynski Y, Galleni M, Hoffmann KM, Bebrone C. 2012. Kinetic and crystallographic studies of extended-spectrum GES-11, GES-12, and GES-14 β-lactamases. Antimicrob Agents Chemother 56:5618–5625.
    155.
    Bontron S, Poirel L, Nordmann P. 2015. In vitro prediction of the evolution of GES-1 β-lactamase hydrolytic activity. Antimicrob Agents Chemother 59:1664–1670.
    156.
    Regan KH, Bhatt J. 2014. Eradication therapy for Burkholderia cepacia complex in people with cystic fibrosis. Cochrane Database Syst Rev 10:CD009876.
    157.
    Dando SJ, Mackay-Sim A, Norton R, Currie BJ, St John JA, Ekberg JA, Batzloff M, Ulett GC, Beacham IR. 2014. Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion. Clin Microbiol Rev 27:691–726.
    158.
    Khan I, Wieler LH, Melzer F, Elschner MC, Muhammad G, Ali S, Sprague LD, Neubauer H, Saqib M. 2013. Glanders in animals: a review on epidemiology, clinical presentation, diagnosis and countermeasures. Transbound Emerg Dis 60:204–221.
    159.
    Dance D. 2014. Treatment and prophylaxis of melioidosis. Int J Antimicrob Agents 43:310–318.
    160.
    Philippon A. 2009. Antibiotic resistance in other non-fermentative strict aerobic Gram-negative bacilli, p 175–211. In Courvalin P, Leclercq R, Rice LB (ed), Antibiogram. ASM Press, Washington, DC.
    161.
    Ho PL, Cheung TK, Yam WC, Yuen KY. 2002. Characterization of a laboratory-generated variant of BPS β-lactamase from Burkholderia pseudomallei that hydrolyses ceftazidime. J Antimicrob Chemother 50:723–726.
    162.
    Tribuddharat C, Moore RA, Baker P, Woods DE. 2003. Burkholderia pseudomallei class A β-lactamase mutations that confer selective resistance against ceftazidime or clavulanic acid inhibition. Antimicrob Agents Chemother 47:2082–2087.
    163.
    Rholl DA, Papp-Wallace KM, Tomaras AP, Vasil ML, Bonomo RA, Schweizer HP. 2011. Molecular investigations of PenA-mediated β-lactam resistance in Burkholderia pseudomallei. Front Microbiol 2:139.
    164.
    Schweizer HP. 2012. Mechanisms of antibiotic resistance in Burkholderia pseudomallei: implications for treatment of melioidosis. Future Microbiol 7:1389–1399.
    165.
    Hwang J, Cho KH, Song H, Yi H, Kim HS. 2014. Deletion mutations conferring substrate spectrum extension in the class A β-lactamase. Antimicrob Agents Chemother 58:6265–6269.
    166.
    Chantratita N, Rholl DA, Sim B, Wuthiekanun V, Limmathurotsakul D, Amornchai P, Thanwisai A, Chua HH, Ooi WF, Holden MT, Day NP, Tan P, Schweizer HP, Peacock SJ. 2011. Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in Burkholderia pseudomallei. Proc Natl Acad Sci U S A 108:17165–17170.
    167.
    Török ME, Chantratita N, Peacock SJ. 2012. Bacterial gene loss as a mechanism for gain of antimicrobial resistance. Curr Opin Microbiol 15:583–587.
    168.
    Aunkham A, Schulte A, Winterhalter M, Suginta W. 2014. Porin involvement in cephalosporin and carbapenem resistance of Burkholderia pseudomallei. PLoS One 9:e95918.
    169.
    Brooke JS. 2012. Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev 25:2–41.
    170.
    Parker AC, Smith CJ. 1993. Genetic and biochemical analysis of a novel Ambler class A β-lactamase responsible for cefoxitin resistance in Bacteroides species. Antimicrob Agents Chemother 37:1028–1036.
    171.
    García N, Gutierrez G, Lorenzo M, Garcia JE, Piriz S, Quesada A. 2008. Genetic determinants for cfxA expression in Bacteroides strains isolated from human infections. J Antimicrob Chemother 62:942–947.
    172.
    Madinier I, Fosse T, Giudicelli J, Labia R. 2001. Cloning and biochemical characterization of a class A β-lactamase from Prevotella intermedia. Antimicrob Agents Chemother 45:2386–2389.
    173.
    Bauernfeind A, Stemplinger I, Jungwirth R, Mangold P, Amann S, Akalin E, Anğ O, Bal C, Casellas JM. 1996. Characterization of β-lactamase gene blaPER-2, which encodes an extended-spectrum class A β-lactamase. Antimicrob Agents Chemother 40:616–620.
    174.
    Bellais S, Poirel L, Leotard S, Naas T, Nordmann P. 2000. Genetic diversity of carbapenem-hydrolyzing metallo-β-lactamases from Chryseobacterium (Flavobacterium) indologenes. Antimicrob Agents Chemother 44:3028–3034.
    175.
    Paterson DL, Bonomo RA. 2005. Extended-spectrum β-lactamases: a clinical update. Clin Microbiol Rev 18:657–686.
    176.
    Hidalgo L, Hopkins KL, Wareham DW, Gutierrez B, Gonzàlez-Zorn B. 2012. Association of extended-spectrum β-lactamase VEB-5 and 16S rRNA methyltransferase armA in Salmonella enterica from the United Kingdom. Antimicrob Agents Chemother 56:4985–4987.
    177.
    Zong Z, Partridge SR, Iredell JR. 2009. A blaVEB-1 variant, blaVEB-6, associated with repeated elements in a complex genetic structure. Antimicrob Agents Chemother 53:1693–1697.
    178.
    Pollitt S, Zalkin H. 1983. Role of primary structure and disulfide bond formation in β-lactamase secretion. J Bacteriol 153:27–32.
    179.
    Schultz SC, Dabadie-McFarkand G, Neitzel JJ, Richards JH. 1987. Stability of wild-type and mutant RTEM-1 β-lactamase: effect of the disulfide bond. Proteins 2:290–297.
    180.
    Bellais S, Poirel L, Naas T, Girlich D, Nordmann P. 2000. Genetic-biochemical analysis and distribution of the Ambler class A β-lactamase CME-2, responsible for extended-spectrum cephalosporin resistance in Chryseobacterium (Flavobacterium) meningosepticum. Antimicrob Agents Chemother 44:1–9.
    181.
    Nordmann P, Mariotte S, Naas T, Labia R, Nicolas MH. 1993. Biochemical properties of a carbapenem-hydrolyzing β-lactamase from Enterobacter cloacae and cloning of the gene into Escherichia coli. Antimicrob Agents Chemother 37:939–946.
    182.
    Kuzin AP, Nukaga M, Nukaga Y, Hujer AM, Bonomo RA, Knox JR. 1999. Structure of the SHV-1 β-lactamase. Biochemistry 38:5720–5727.
    183.
    Nukaga M, Mayama K, Hujer AM, Bonomo RA, Knox JR. 2003. Ultrahigh resolution structure of a class A β-lactamase: on the mechanism and specificity of the extended-spectrum SHV-2 enzyme. J Mol Biol 328:289–301.
    184.
    Bouthors AT, Dagoneau-Blanchard N, Naas T, Nordmann P, Jarlier V, Sougakoff W. 1998. Role of residues 104, 164, 166, 238 and 240 in the substrate profile of PER-1 β-lactamase hydrolysing third-generation cephalosporins. Biochem J 330:1443–1449.
    185.
    Chen CC, Herzberg O. 1992. Inhibition of β-lactamase by clavulanate. Trapped intermediates in cryocrystallographic studies. J Mol Biol 224:1103–1113.
    186.
    Jelsch C, Mourey L, Masson JM, Samama JP. 1993. Crystal structure of Escherichia coli TEM-1 β-lactamase at 1.8 A resolution. Proteins 16:364–383.
    187.
    Liang YH, Gao R, Su XD. 2012. Structural insights into the broadened substrate profile of the extended-spectrum β-lactamase OXY-1-1 from Klebsiella oxytoca. Acta Crystallogr D Biol Crystallogr 68:1460–1467.
    188.
    Qing Y, Cao KY, Fang ZL, Huang YM, Zhang XF, Tian GB, Huang X. 2014. Outbreak of PER-1 and diversity of β-lactamases among ceftazidime-resistant Pseudomonas aeruginosa clinical isolates. J Med Microbiol 63:386–392.
    189.
    Opazo A, Vali L, Al Obaid K, Dashti AA, Amyes SG. 2014. Novel genetic structure harbouring blaPER-1 in ceftazidime-resistant Acinetobacter baumannii isolated from Kuwait. Int J Antimicrob Agents 43:383–384.
    190.
    Mnif B, Ktari S, Chaari A, Medhioub F, Rhimi F, Bouaziz M, Hammami A. 2013. Nosocomial dissemination of Providencia stuartii isolates carrying blaOXA-48, blaPER-1, blaCMY-4 and qnrA6 in a Tunisian hospital. J Antimicrob Chemother 68:329–332.
    191.
    Fabre M, Hauck Y, Soler C, Koeck JL, van Ingen J, van Soolingen D, Vergnaud G, Pourcel C. 2010. Molecular characteristics of “Mycobacterium canettii” the smooth Mycobacterium tuberculosis bacilli. Infect Genet Evol 10:1165–1173.
    192.
    Papp-Wallace KM, Taracila M, Hornick JM, Hujer AM, Hujer KM, Distler AM, Endimiani A, Bonomo RA. 2010. Substrate selectivity and a novel role in inhibitor discrimination by residue 237 in the KPC-2 β-lactamase. Antimicrob Agents Chemother 54:2867–2877.
    193.
    Bouthors AT, Delettré J, Mugnier P, Jarlier V, Sougakoff W. 1999. Site-directed mutagenesis of residues 164, 170, 171, 179, 220, 237 and 242 in PER-1 β-lactamase hydrolysing expanded-spectrum cephalosporins. Protein Eng 12:313–318.
    194.
    Bouthors AT, Jarlier V, Sougakoff W. 1998. Amino acid substitutions at positions 69, 165, 244 and 275 of the PER-1 β-lactamase do not impair enzyme inactivation by clavulanate. J Antimicrob Chemother 42:399–401.
    195.
    Goffin C, Ghuysen JM. 1998. Multimodular penicillin-binding proteins: an enigmatic family of orthologs and paralogs. Microbiol Mol Biol Rev 62:1079–1093.
    196.
    Edgar RC. 2004. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797.
    197.
    Waterhouse AM, Procter JB, Martin DM, Clamp M, Barton GJ. 2009. Jalview version 2—a multiple sequence alignment editor and analysis workbench. Bioinformatics 25:1189–1191.

    Author Bios

    Alain Philippon [email protected]
    Faculté de Médecine Paris Descartes, Service de Bactériologie, Paris, France
    Alain Philippon is a veterinarian who prepared his Ph.D. thesis at the Commissariat à l'Energie Atomique (CEA) in 1965. Initially trained on Brucella and brucellosis at Nouzilly (Institut National de la Recherche Agronomique/INRA) between 1966 and 1970, he started to analyze bacterial resistance to antibiotics, mostly to β-lactams (susceptibility patterns, ESBL, and plasmid-encoded AmpC) at CHU Cochin, Paris, France, in 1972. As Professor Emeritus of Microbiology at the University of Paris Descartes and previous Head of the Bacteriology Laboratory at Hopital Cochin, he published more than 200 scientific papers and mentored 20 doctoral and postdoctoral researchers. He was also codirector of a course on medical bacteriology at Institut Pasteur for a decade.
    Patrick Slama
    Independent Researcher, Paris, France
    Patrick Slama was trained as a Physical Chemist at Ecole Normale Supérieure in Lyon, France. He obtained a M.S. in Chemical Biology, creating synthetic models for copper-containing enzymes, and a Ph.D., still with Dr. Réglier at Université Aix-Marseilles, studying the role of the reduction cosubstrate for the copper-containing enzyme dopamine β-hydroxylase in its activation and inactivation. He later obtained postdoctoral positions with Dr. Vernier, Dr. Sidhu, and Dr. Giros in Créteil, France, studying the regulation of presynaptic monoamine transporters. He next moved to bioinformatics and translational research, studying sequence-function relationships in proteins, at the Max Planck Institute in Berlin, Germany, and at Johns Hopkins University, Baltimore, MD, with Professor Geman. There, he developed new tools for the analysis of protein multiple-sequence alignments as well as for proteomics analysis. He now dedicates a significant part of his time to Photography.
    Paul Dény
    Université Paris 3, UFR SMBH, Groupe des Hôpitaux Universitaires Paris—Seine Saint Denis, Centre de Recherches en Cancérologie de Lyon INSERM U1052 UMR CNRS 5286, Lyon, France
    Paul Dény is a medical microbiologist at Universities Paris 6 and 7. He is specialized in hepatitis viruses and hepatitis delta virus (HDV), a satellite of hepatitis B virus (HBV), since his Ph.D. under Christian Bréchot at Institut Pasteur, Paris, France, unit of Pierre Tiollais. As a professor in Bacteriology and Virology, he created and developed the Virology Unit at University Paris 13/SPC—Avicenne Hospital, from 1988 to 2008, as head of the laboratory. He defined HDV taxonomy, composed of 8 major clades, referred as genotypes. He has been involved in the extensive characterization of nurse-to-patient transmission of HIV-1 and the emergence of hepatitis C virus genotype 4 (HCV-4) in France and participated in the development of an algorithm for the detection of recombination in circular HBV sequences. In 2007, he joined the Cancer Research Center in Lyon, INSERM U1052-CNRS 5286, to develop cell culture models for HBV and HDV. He has been involved in evolutionary analysis since 1994.
    Roger Labia
    Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, Quimper, France
    Roger Labia graduated from the world-renowned Ecole Polytechnique in Paris, France (1962 to 1964), with specialization in mathematics, physics, and chemistry. In relation with his high and early interest in chemical and biological problems, he joined scientific research, first at the Pasteur Institute (starting in 1965). In 1969, he received a Ph.D., studying the organic synthesis of natural compounds. Subsequently, he spent one postdoctoral year at Ottawa University, Canada (1969 to 1970), where he began studying biochemistry and bacteriology. Back in France, he started a research program on antibiotics, including their mode of action and mechanisms of resistance. This allowed him to develop multiple collaborations with chemists and bacteriologists from France and other countries. He has published more than 320 scientific papers, mostly in high-impact international journals. He has been involved in teaching and directed about 50 theses.

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    Clinical Microbiology Reviews
    Volume 29Number 1January 2016
    Pages: 29 - 57

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    Published online: 28 October 2015

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    Alain Philippon [email protected]
    Faculté de Médecine Paris Descartes, Service de Bactériologie, Paris, France
    Patrick Slama
    Independent Researcher, Paris, France
    Paul Dény
    Université Paris 3, UFR SMBH, Groupe des Hôpitaux Universitaires Paris—Seine Saint Denis, Centre de Recherches en Cancérologie de Lyon INSERM U1052 UMR CNRS 5286, Lyon, France
    Roger Labia
    Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, Quimper, France

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  • Clinical Microbiology ReviewsArticle
    The Role of the BCL-2 Family of Proteins in HIV-1 Pathogenesis and Persistence

    The Role of the BCL-2 Family of Proteins in HIV-1 Pathogenesis and Persistence

    SUMMARY

    Advances in HIV-1 therapy have transformed the once fatal infection into a manageable, chronic condition, yet the search for a widely applicable approach to cure remains elusive. The ineffectiveness of antiretroviral therapy (ART) in reducing the size of the HIV-1 latent reservoir has prompted investigation into the mechanisms of HIV-1 latency and immune escape. One of the major regulators of apoptosis, the BCL-2 protein, alongside its homologous family members, is a major target of HIV-1-induced change. Recent studies have now demonstrated the association of this protein with cells that support proviral forms in the setting of latency and have helped identify BCL-2 as a novel and promising therapeutic target for HIV-1 therapy directed at possible cure. This review aims to systematically review the interactions of HIV-1 with BCL-2 and its homologs and to examine the possibility of using BCL-2 inhibitors in the study and elimination of the latent reservoir.

    REFERENCES

    1.
    Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L. 1983. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220:868–871.
    2.
    Cummins NW, Badley AD. 2010. Mechanisms of HIV-associated lymphocyte apoptosis: 2010. Cell Death Dis 1:e99.
    3.
    Dinkins C, Arko-Mensah J, Deretic V. 2010. Autophagy and HIV. Semin Cell Dev Biol 21:712–718.
    4.
    Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, Hunt PW, Hatano H, Sowinski S, Munoz-Arias I, Greene WC. 2014. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 505:509–514.
    5.
    Pan T, Wu S, He X, Luo H, Zhang Y, Fan M, Geng G, Ruiz VC, Zhang J, Mills L, Bai C, Zhang H. 2014. Necroptosis takes place in human immunodeficiency virus type-1 (HIV-1)-infected CD4+ T lymphocytes. PLoS One 9:e93944.
    6.
    Davey RT, Jr, Bhat N, Yoder C, Chun TW, Metcalf JA, Dewar R, Natarajan V, Lempicki RA, Adelsberger JW, Miller KD, Kovacs JA, Polis MA, Walker RE, Falloon J, Masur H, Gee D, Baseler M, Dimitrov DS, Fauci AS, Lane HC. 1999. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci U S A 96:15109–15114.
    7.
    Siliciano RF, Greene WC. 2011. HIV latency. Cold Spring Harb Perspect Med 1:a007096.
    8.
    Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. 1984. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 226:1097–1099.
    9.
    Vaux DL, Cory S, Adams JM. 1988. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 335:440–442.
    10.
    Oltvai ZN, Milliman CL, Korsmeyer SJ. 1993. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619.
    11.
    Hardwick JM, Soane L. 2013. Multiple functions of BCL-2 family proteins. Cold Spring Harb Perspect Biol 5:a008722.
    12.
    Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, Annicchiarico-Petruzzelli M, Antonov AV, Arama E, Baehrecke EH, Barlev NA, Bazan NG, Bernassola F, Bertrand MJM, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Boya P, Brenner C, Campanella M, Candi E, Carmona-Gutierrez D, Cecconi F, Chan FK-M, Chandel NS, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Cohen GM, Conrad M, Cubillos-Ruiz JR, Czabotar PE, D'Angiolella V, Dawson TM, Dawson VL, De Laurenzi V, De Maria R, Debatin K-M, DeBerardinis RJ, Deshmukh M, Di Daniele N, Di Virgilio F, Dixit VM, Dixon SJ, et al. 2018. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 25:486–541.
    13.
    Elmore S. 2007. Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516.
    14.
    Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N. 2014. Apoptosis and molecular targeting therapy in cancer. Biomed Res Int 2014:150845.
    15.
    Hengartner MO. 2000. The biochemistry of apoptosis. Nature 407:770–776.
    16.
    Julien O, Wells JA. 2017. Caspases and their substrates. Cell Death Differ 24:1380–1389.
    17.
    Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, Houtzager VM, Nordstrom PA, Roy S, Vaillancourt JP, Chapman KT, Nicholson DW. 1997. A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J Biol Chem 272:17907–17911.
    18.
    Cory S, Adams JM. 2002. The BclII family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656.
    19.
    Adams JM, Cory S. 2018. The BCL-2 arbiters of apoptosis and their growing role as cancer targets. Cell Death Differ 25:27–36.
    20.
    Cost GJ, Freyvert Y, Vafiadis A, Santiago Y, Miller JC, Rebar E, Collingwood TN, Snowden A, Gregory PD. 2010. BAK and BAX deletion using zinc-finger nucleases yields apoptosis-resistant CHO cells. Biotechnol Bioeng 105:330–340.
    21.
    Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ. 2001. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:727–730.
    22.
    Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ. 2002. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2:183–192.
    23.
    Bouillet P, Strasser A. 2002. BH3-only proteins—evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death. J Cell Sci 115(Pt 8):1567–1574.
    24.
    Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC. 2005. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell 17:393–403.
    25.
    Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, Adams JM, Huang DC. 2005. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev 19:1294–1305.
    26.
    Willis SN, Fletcher JI, Kaufmann T, van Delft MF, Chen L, Czabotar PE, Ierino H, Lee EF, Fairlie WD, Bouillet P, Strasser A, Kluck RM, Adams JM, Huang DC. 2007. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315:856–859.
    27.
    Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, Herman B, Levine B. 1998. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol 72:8586–8596.
    28.
    Maiuri MC, Le Toumelin G, Criollo A, Rain JC, Gautier F, Juin P, Tasdemir E, Pierron G, Troulinaki K, Tavernarakis N, Hickman JA, Geneste O, Kroemer G. 2007. Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J 26:2527–2539.
    29.
    Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD, Levine B. 2005. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927–939.
    30.
    Chipuk JE, Bouchier-Hayes L, Green DR. 2006. Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario. Cell Death Differ 13:1396–1402.
    31.
    Shamas-Din A, Kale J, Leber B, Andrews DW. 2013. Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb Perspect Biol 5:a008714.
    32.
    Leber B, Lin J, Andrews DW. 2007. Embedded together: the life and death consequences of interaction of the Bcl-2 family with membranes. Apoptosis 12:897–911.
    33.
    Llambi F, Moldoveanu T, Tait SW, Bouchier-Hayes L, Temirov J, McCormick LL, Dillon CP, Green DR. 2011. A unified model of mammalian BCL-2 protein family interactions at the mitochondria. Mol Cell 44:517–531.
    34.
    Hsu H, Xiong J, Goeddel DV. 1995. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81:495–504.
    35.
    Johnstone RW, Frew AJ, Smyth MJ. 2008. The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer 8:782–798.
    36.
    Tummers B, Green DR. 2017. Caspase-8: regulating life and death. Immunol Rev 277:76–89.
    37.
    Kischkel FC, Hellbardt S, Behrmann I, Germer M, Pawlita M, Krammer PH, Peter ME. 1995. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J 14:5579–5588.
    38.
    Khan KH, Blanco-Codesido M, Molife LR. 2014. Cancer therapeutics: targeting the apoptotic pathway. Crit Rev Oncol Hematol 90:200–219.
    39.
    Wu CC, Bratton SB. 2013. Regulation of the intrinsic apoptosis pathway by reactive oxygen species. Antioxid Redox Signal 19:546–558.
    40.
    Shimizu S, Narita M, Tsujimoto Y. 1999. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 399:483–487.
    41.
    Sattler M, Liang H, Nettesheim D, Meadows RP, Harlan JE, Eberstadt M, Yoon HS, Shuker SB, Chang BS, Minn AJ, Thompson CB, Fesik SW. 1997. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science 275:983–986.
    42.
    Gavathiotis E, Reyna DE, Davis ML, Bird GH, Walensky LD. 2010. BH3-triggered structural reorganization drives the activation of proapoptotic BAX. Mol Cell 40:481–492.
    43.
    Kim H, Tu HC, Ren D, Takeuchi O, Jeffers JR, Zambetti GP, Hsieh JJ, Cheng EH. 2009. Stepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis. Mol Cell 36:487–499.
    44.
    Gibson CJ, Davids MS. 2015. BCL-2 antagonism to target the intrinsic mitochondrial pathway of apoptosis. Clin Cancer Res 21:5021–5029.
    45.
    Czabotar PE, Westphal D, Dewson G, Ma S, Hockings C, Fairlie WD, Lee EF, Yao S, Robin AY, Smith BJ, Huang DC, Kluck RM, Adams JM, Colman PM. 2013. Bax crystal structures reveal how BH3 domains activate Bax and nucleate its oligomerization to induce apoptosis. Cell 152:519–531.
    46.
    Jiang X, Wang X. 2004. Cytochrome c-mediated apoptosis. Annu Rev Biochem 73:87–106.
    47.
    Schenk RL, Strasser A, Dewson G. 2017. BCL-2: long and winding path from discovery to therapeutic target. Biochem Biophys Res Commun 482:459–469.
    48.
    Sakahira H, Enari M, Nagata S. 1998. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature 391:96–99.
    49.
    Cummins NW, Badley AD. 2014. Making sense of how HIV kills infected CD4 T cells: implications for HIV cure. Mol Cell Ther 2:20.
    50.
    Re M, Gibellini D, Aschbacher R, Vignoli M, Furlini G, Ramazzotti E, Bertolaso L, La Placa M. 1998. High levels of HIV-1 replication show a clear correlation with downmodulation of Bcl-2 protein in peripheral blood lymphocytes of HIV-1-seropositive subjects. J Med Virol 56:66–73.
    51.
    Boudet F, Lecoeur H, Gougeon ML. 1996. Apoptosis associated with ex vivo down-regulation of Bcl-2 and up-regulation of Fas in potential cytotoxic CD8+ T lymphocytes during HIV infection. J Immunol 156:2282–2293.
    52.
    Dobmeyer TS, Klein SA, Dobmeyer JM, Raffel B, Findhammer S, Hoelzer D, Helm EB, Rossol R, Kabelitz D. 1998. Differential expression of bcl-2 and susceptibility to programmed cell death in lymphocytes of HIV-1-infected individuals. Clin Immunol Immunopathol 87:230–239.
    53.
    Scheuring UJ, Sabzevari H, Corbeil J, Theofilopoulos AN. 1999. Differential expression profiles of apoptosis-affecting genes in HIV-infected cell lines and patient T cells. AIDS 13:167–175.
    54.
    Regamey N, Harr T, Battegay M, Erb P. 1999. Downregulation of Bcl-2, but not of Bax or Bcl-x, is associated with T lymphocyte apoptosis in HIV infection and restored by antiretroviral therapy or by interleukin 2. AIDS Res Hum Retroviruses 15:803–810.
    55.
    Zaunders JJ, Munier ML, Kaufmann DE, Ip S, Grey P, Smith D, Ramacciotti T, Quan D, Finlayson R, Kaldor J, Rosenberg ES, Walker BD, Cooper DA, Kelleher AD. 2005. Early proliferation of CCR5(+) CD38(+++) antigen-specific CD4(+) Th1 effector cells during primary HIV-1 infection. Blood 106:1660–1667.
    56.
    Yue FY, Kovacs CM, Dimayuga RC, Gu XX, Parks P, Kaul R, Ostrowski MA. 2005. Preferential apoptosis of HIV-1-specific CD4+ T cells. J Immunol 174:2196–2204.
    57.
    Sieg SF, Bazdar DA, Lederman MM. 2008. S-phase entry leads to cell death in circulating T cells from HIV-infected persons. J Leukoc Biol 83:1382–1387.
    58.
    Palmer CS, Duette GA, Wagner MCE, Henstridge DC, Saleh S, Pereira C, Zhou J, Simar D, Lewin SR, Ostrowski M, McCune JM, Crowe SM. 2017. Metabolically active CD4+ T cells expressing Glut1 and OX40 preferentially harbor HIV during in vitro infection. FEBS Lett 591:3319–3332.
    59.
    Rogers PR, Song J, Gramaglia I, Killeen N, Croft M. 2001. OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells. Immunity 15:445–455.
    60.
    Haas MK, Levy DN, Folkvord JM, Connick E. 2015. Distinct patterns of Bcl-2 expression occur in R5- and X4-tropic HIV-1-producing lymphoid tissue cells infected ex vivo. AIDS Res Hum Retroviruses 31:298–304.
    61.
    Petrovas C, Mueller YM, Dimitriou ID, Bojczuk PM, Mounzer KC, Witek J, Altman JD, Katsikis PD. 2004. HIV-specific CD8+ T cells exhibit markedly reduced levels of Bcl-2 and Bcl-xL. J Immunol 172:4444–4453.
    62.
    Petrovas C, Mueller YM, Dimitriou ID, Altork SR, Banerjee A, Sklar P, Mounzer KC, Altman JD, Katsikis PD. 2007. Increased mitochondrial mass characterizes the survival defect of HIV-specific CD8(+) T cells. Blood 109:2505–2513.
    63.
    Doisne JM, Urrutia A, Lacabaratz-Porret C, Goujard C, Meyer L, Chaix ML, Sinet M, Venet A. 2004. CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection. J Immunol 173:2410–2418.
    64.
    Lecuroux C, Girault I, Boutboul F, Urrutia A, Goujard C, Meyer L, Lambotte O, Chaix ML, Martinez V, Autran B, Sinet M, Venet A. 2009. Antiretroviral therapy initiation during primary HIV infection enhances both CD127 expression and the proliferative capacity of HIV-specific CD8+ T cells. AIDS 23:1649–1658.
    65.
    Colle JH, Moreau JL, Fontanet A, Lambotte O, Joussemet M, Jacod S, Delfraissy JF, Theze J. 2006. Regulatory dysfunction of the interleukin-7 receptor in CD4 and CD8 lymphocytes from HIV-infected patients—effects of antiretroviral therapy. J Acquir Immune Defic Syndr 42:277–285.
    66.
    Yan J, Sabbaj S, Bansal A, Amatya N, Shacka JJ, Goepfert PA, Heath SL. 2013. HIV-specific CD8+ T cells from elite controllers are primed for survival. J Virol 87:5170–5181.
    67.
    Derby N, Martinelli E, Robbiani M. 2011. Myeloid dendritic cells in HIV-1 infection. Curr Opin HIV AIDS 6:379–384.
    68.
    Dillon SM, Friedlander LJ, Rogers LM, Meditz AL, Folkvord JM, Connick E, McCarter MD, Wilson CC. 2011. Blood myeloid dendritic cells from HIV-1-infected individuals display a proapoptotic profile characterized by decreased Bcl-2 levels and by caspase-3+ frequencies that are associated with levels of plasma viremia and T cell activation in an exploratory study. J Virol 85:397–409.
    69.
    Aillet F, Masutani H, Elbim C, Raoul H, Chêne L, Nugeyre MT, Paya C, Barré-Sinoussi F, Gougerot-Pocidalo MA, Israël N. 1998. Human immunodeficiency virus induces a dual regulation of Bcl-2, resulting in persistent infection of CD4(+) T- or monocytic cell lines. J Virol 72:9698–9705.
    70.
    Guillemard E, Jacquemot C, Aillet F, Schmitt N, Barré-Sinoussi F, Israël N. 2004. Human immunodeficiency virus 1 favors the persistence of infection by activating macrophages through TNF. Virology 329:371–380.
    71.
    Castellano P, Prevedel L, Eugenin EA. 2017. HIV-infected macrophages and microglia that survive acute infection become viral reservoirs by a mechanism involving Bim. Sci Rep 7:12866.
    72.
    Yuan Z, Syed MA, Panchal D, Joo M, Colonna M, Brantly M, Sadikot RT. 2014. Triggering receptor expressed on myeloid cells 1 (TREM-1)-mediated Bcl-2 induction prolongs macrophage survival. J Biol Chem 289:15118–15129.
    73.
    Yuan Z, Fan X, Staitieh B, Bedi C, Spearman P, Guidot DM, Sadikot RT. 2017. HIV-related proteins prolong macrophage survival through induction of Triggering receptor expressed on myeloid cells-1. Sci Rep 7:42028.
    74.
    Carter CC, Onafuwa-Nuga A, McNamara LA, Riddell J, Bixby D, Savona MR, Collins KL. 2010. HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs. Nat Med 16:446–451.
    75.
    Lauria F, Raspadori D, Rondelli D, Ventura MA, Fiacchini M, Visani G, Forconi F, Tura S. 1997. High bcl-2 expression in acute myeloid leukemia cells correlates with CD34 positivity and complete remission rate. Leukemia 11:2075–2078.
    76.
    Garg H, Mohl J, Joshi A. 2012. HIV-1 induced bystander apoptosis. Viruses 4:3020–3043.
    77.
    Hashimoto F, Oyaizu N, Kalyanaraman VS, Pahwa S. 1997. Modulation of Bcl-2 protein by CD4 cross-linking: a possible mechanism for lymphocyte apoptosis in human immunodeficiency virus infection and for rescue of apoptosis by interleukin-2. Blood 90:745–753.
    78.
    Perfettini JL, Roumier T, Castedo M, Larochette N, Boya P, Raynal B, Lazar V, Ciccosanti F, Nardacci R, Penninger J, Piacentini M, Kroemer G. 2004. NF-kappaB and p53 are the dominant apoptosis-inducing transcription factors elicited by the HIV-1 envelope. J Exp Med 199:629–640.
    79.
    Blanco J, Barretina J, Ferri KF, Jacotot E, Gutiérrez A, Armand-Ugón M, Cabrera C, Kroemer G, Clotet B, Esté JA. 2003. Cell-surface-expressed HIV-1 envelope induces the death of CD4 T cells during GP41-mediated hemifusion-like events. Virology 305:318–329.
    80.
    Castedo M, Ferri KF, Blanco J, Roumier T, Larochette N, Barretina J, Amendola A, Nardacci R, Metivier D, Este JA, Piacentini M, Kroemer G. 2001. Human immunodeficiency virus 1 envelope glycoprotein complex-induced apoptosis involves mammalian target of rapamycin/FKBP12-rapamycin-associated protein-mediated p53 phosphorylation. J Exp Med 194:1097–1110.
    81.
    Perfettini JL, Castedo M, Roumier T, Andreau K, Nardacci R, Piacentini M, Kroemer G. 2005. Mechanisms of apoptosis induction by the HIV-1 envelope. Cell Death Differ 12(Suppl 1):916–923.
    82.
    Zauli G, Gibellini D, Caputo A, Bassini A, Negrini M, Monne M, Mazzoni M, Capitani S. 1995. The human immunodeficiency virus type-1 Tat protein upregulates Bcl-2 gene expression in Jurkat T-cell lines and primary peripheral blood mononuclear cells. Blood 86:3823–3834.
    83.
    Zauli G, Gibellini D. 1996. The human immunodeficiency virus type-1 (HIV-1) Tat protein and Bcl-2 gene expression. Leuk Lymphoma 23:551–560.
    84.
    López-Huertas MR, Mateos E, Sánchez Del Cojo M, Gómez-Esquer F, Díaz-Gil G, Rodríguez-Mora S, López JA, Calvo E, López-Campos G, Alcamí J, Coiras M. 2013. The presence of HIV-1 Tat protein second exon delays Fas protein-mediated apoptosis in CD4+ T lymphocytes: a potential mechanism for persistent viral production. J Biol Chem 288:7626–7644.
    85.
    Zheng L, Yang Y, Guocai L, Pauza CD, Salvato MS. 2007. HIV Tat protein increases Bcl-2 expression in monocytes which inhibits monocyte apoptosis induced by tumor necrosis factor-alpha-related apoptosis-induced ligand. Intervirology 50:224–228.
    86.
    Chen D, Wang M, Zhou S, Zhou Q. 2002. HIV-1 Tat targets microtubules to induce apoptosis, a process promoted by the pro-apoptotic Bcl-2 relative Bim. EMBO J 21:6801–6810.
    87.
    Dabrowska A, Kim N, Aldovini A. 2008. Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T lymphocytes. J Immunol 181:8460–8477.
    88.
    Sastry KJ, Marin MC, Nehete PN, McConnell K, el-Naggar AK, McDonnell TJ. 1996. Expression of human immunodeficiency virus type I tat results in down-regulation of bcl-2 and induction of apoptosis in hematopoietic cells. Oncogene 13:487–493.
    89.
    Sforza F, Nicoli F, Gallerani E, Finessi V, Reali E, Cafaro A, Caputo A, Ensoli B, Gavioli R. 2014. HIV-1 Tat affects the programming and functionality of human CD8(+) T cells by modulating the expression of T-box transcription factors. AIDS 28:1729–1738.
    90.
    Rasola A, Gramaglia D, Boccaccio C, Comoglio PM. 2001. Apoptosis enhancement by the HIV-1 Nef protein. J Immunol 166:81–88.
    91.
    Wolf D, Witte V, Laffert B, Blume K, Stromer E, Trapp S, d'Aloja P, Schürmann A, Baur AS. 2001. HIV-1 Nef associated PAK and PI3-kinases stimulate Akt-independent Bad-phosphorylation to induce anti-apoptotic signals. Nat Med 7:1217–1224.
    92.
    Ndolo T, Dhillon NK, Nguyen H, Guadalupe M, Mudryj M, Dandekar S. 2002. Simian immunodeficiency virus Nef protein delays the progression of CD4+ T cells through G1/S phase of the cell cycle. J Virol 76:3587–3595.
    93.
    Greenway AL, McPhee DA, Allen K, Johnstone R, Holloway G, Mills J, Azad A, Sankovich S, Lambert P. 2002. Human immunodeficiency virus type 1 Nef binds to tumor suppressor p53 and protects cells against p53-mediated apoptosis. J Virol 76:2692–2702.
    94.
    Hemann MT, Lowe SW. 2006. The p53-Bcl-2 connection. Cell Death Differ 13:1256–1259.
    95.
    Kyei GB, Dinkins C, Davis AS, Roberts E, Singh SB, Dong C, Wu L, Kominami E, Ueno T, Yamamoto A, Federico M, Panganiban A, Vergne I, Deretic V. 2009. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J Cell Biol 186:255–268.
    96.
    Strack PR, Frey MW, Rizzo CJ, Cordova B, George HJ, Meade R, Ho SP, Corman J, Tritch R, Korant BD. 1996. Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2. Proc Natl Acad Sci U S A 93:9571–9576.
    97.
    Nie Z, Phenix BN, Lum JJ, Alam A, Lynch DH, Beckett B, Krammer PH, Sekaly RP, Badley AD. 2002. HIV-1 protease processes procaspase 8 to cause mitochondrial release of cytochrome c, caspase cleavage and nuclear fragmentation. Cell Death Differ 9:1172–1184.
    98.
    Nie Z, Bren GD, Vlahakis SR, Schimnich AA, Brenchley JM, Trushin SA, Warren S, Schnepple DJ, Kovacs CM, Loutfy MR, Douek DC, Badley AD. 2007. Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo. J Virol 81:6947–6956.
    99.
    Sainski AM, Dai H, Natesampillai S, Pang YP, Bren GD, Cummins NW, Correia C, Meng XW, Tarara JE, Ramirez-Alvarado M, Katzmann DJ, Ochsenbauer C, Kappes JC, Kaufmann SH, Badley AD. 2014. Casp8p41 generated by HIV protease kills CD4 T cells through direct Bak activation. J Cell Biol 206:867–876.
    100.
    Cummins NW, Sainski AM, Dai H, Natesampillai S, Pang Y-P, Bren GD, de Araujo Correia MCM, Sampath R, Rizza SA, O'Brien D, Yao JD, Kaufmann SH, Badley AD. 2016. Prime, shock, and kill: priming CD4 T cells from HIV patients with a BCL-2 antagonist before HIV reactivation reduces HIV reservoir size. J Virol 90:4032–4048.
    101.
    Montal M. 2003. Structure-function correlates of Vpu, a membrane protein of HIV-1. FEBS Lett 552:47–53.
    102.
    Raja NU, Jabbar MA. 1996. The human immunodeficiency virus type 1 Vpu protein tethered to the CD4 extracellular domain is localized to the plasma membrane and is biologically active in the secretory pathway of mammalian cells: implications for the mechanisms of Vpu function. Virology 220:141–151.
    103.
    Akari H, Bour S, Kao S, Adachi A, Strebel K. 2001. The human immunodeficiency virus type 1 accessory protein Vpu induces apoptosis by suppressing the nuclear factor kappaB-dependent expression of antiapoptotic factors. J Exp Med 194:1299–1311.
    104.
    Andersen JL, DeHart JL, Zimmerman ES, Ardon O, Kim B, Jacquot G, Benichou S, Planelles V. 2006. HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. PLoS Pathog 2:e127.
    105.
    Ayyavoo V, Mahboubi A, Mahalingam S, Ramalingam R, Kudchodkar S, Williams WV, Green DR, Weiner DB. 1997. HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor kappa B. Nat Med 3:1117–1123.
    106.
    Conti L, Rainaldi G, Matarrese P, Varano B, Rivabene R, Columba S, Sato A, Belardelli F, Malorni W, Gessani S. 1998. The HIV-1 vpr protein acts as a negative regulator of apoptosis in a human lymphoblastoid T cell line: possible implications for the pathogenesis of AIDS. J Exp Med 187:403–413.
    107.
    Pace MJ, Graf EH, Agosto LM, Mexas AM, Male F, Brady T, Bushman FD, O'Doherty U. 2012. Directly infected resting CD4+ T cells can produce HIV Gag without spreading infection in a model of HIV latency. PLoS Pathog 8:e1002818.
    108.
    DeMaster LK, Liu X, VanBelzen DJ, Trinité B, Zheng L, Agosto LM, Migueles SA, Connors M, Sambucetti L, Levy DN, Pasternak AO, O'Doherty U. 2016. A subset of CD4/CD8 double-negative T cells expresses HIV proteins in patients on antiretroviral therapy. J Virol 90:2165–2179.
    109.
    Freeman ML, Shive CL, Nguyen TP, Younes S-A, Panigrahi S, Lederman MM. 2016. Cytokines and T-cell homeostasis in HIV infection. J Infect Dis 214(Suppl 2):S51–S57.
    110.
    Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, Duan S, Eiwegger T, Eljaszewicz A, Ferstl R, Frei R, Garbani M, Globinska A, Hess L, Huitema C, Kubo T, Komlosi Z, Konieczna P, Kovacs N, Kucuksezer UC, Meyer N, Morita H, Olzhausen J, O'Mahony L, Pezer M, Prati M, Rebane A, Rhyner C, Rinaldi A, Sokolowska M, Stanic B, Sugita K, Treis A, van de Veen W, Wanke K, Wawrzyniak M, Wawrzyniak P, Wirz OF, Zakzuk JS, Akdis CA. 2016. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor beta, and TNF-alpha: receptors, functions, and roles in diseases. J Allergy Clin Immunol 138:984–1010.
    111.
    Imami N, Antonopoulos C, Hardy GA, Gazzard B, Gotch FM. 1999. Assessment of type 1 and type 2 cytokines in HIV type 1-infected individuals: impact of highly active antiretroviral therapy. AIDS Res Hum Retroviruses 15:1499–1508.
    112.
    Gómez J, Martínez AC, González A, García A, Rebollo A. 1998. The Bcl-2 gene is differentially regulated by IL-2 and IL-4: role of the transcription factor NF-AT. Oncogene 17:1235–1243.
    113.
    Cohen SB, Crawley JB, Kahan MC, Feldmann M, Foxwell BM. 1997. Interleukin-10 rescues T cells from apoptotic cell death: association with an upregulation of Bcl-2. Immunology 92:1–5.
    114.
    Brockman MA, Kwon DS, Tighe DP, Pavlik DF, Rosato PC, Sela J, Porichis F, Le Gall S, Waring MT, Moss K, Jessen H, Pereyra F, Kavanagh DG, Walker BD, Kaufmann DE. 2009. IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells. Blood 114:346–356.
    115.
    Shive CL, Mudd JC, Funderburg NT, Sieg SF, Kyi B, Bazdar DA, Mangioni D, Gori A, Jacobson JM, Brooks AD, Hardacre J, Ammori J, Estes JD, Schacker TW, Rodriguez B, Lederman MM. 2014. Inflammatory cytokines drive CD4+ T-cell cycling and impaired responsiveness to interleukin 7: implications for immune failure in HIV disease. J Infect Dis 210:619–629.
    116.
    Shive CL, Clagett B, McCausland MR, Mudd JC, Funderburg NT, Freeman ML, Younes S-A, Ferrari BM, Rodriguez B, McComsey GA, Calabrese LH, Sieg SF, Lederman MM. 2016. Inflammation perturbs the IL-7 axis, promoting senescence and exhaustion that broadly characterize immune failure in treated HIV infection. J Acquir Immune Defic Syndr 71:483–492.
    117.
    Wojciechowski S, Tripathi P, Bourdeau T, Acero L, Grimes HL, Katz JD, Finkelman FD, Hildeman DA. 2007. Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis. J Exp Med 204:1665–1675.
    118.
    Bradley LM, Haynes L, Swain SL. 2005. IL-7: maintaining T-cell memory and achieving homeostasis. Trends Immunol 26:172–176.
    119.
    Vandergeeten C, Fromentin R, DaFonseca S, Lawani MB, Sereti I, Lederman MM, Ramgopal M, Routy JP, Sekaly RP, Chomont N. 2013. Interleukin-7 promotes HIV persistence during antiretroviral therapy. Blood 121:4321–4329.
    120.
    Fraietta JA, Mueller YM, Yang G, Boesteanu AC, Gracias DT, Do DH, Hope JL, Kathuria N, McGettigan SE, Lewis MG, Giavedoni LD, Jacobson JM, Katsikis PD. 2013. Type I interferon upregulates Bak and contributes to T cell loss during human immunodeficiency virus (HIV) infection. PLoS Pathog 9:e1003658.
    121.
    Sandler NG, Bosinger SE, Estes JD, Zhu RT, Tharp GK, Boritz E, Levin D, Wijeyesinghe S, Makamdop KN, del Prete GQ, Hill BJ, Timmer JK, Reiss E, Yarden G, Darko S, Contijoch E, Todd JP, Silvestri G, Nason M, Norgren RB, Jr, Keele BF, Rao S, Langer JA, Lifson JD, Schreiber G, Douek DC. 2014. Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature 511:601–605.
    122.
    Hardy GA, Sieg S, Rodriguez B, Anthony D, Asaad R, Jiang W, Mudd J, Schacker T, Funderburg NT, Pilch-Cooper HA, Debernardo R, Rabin RL, Lederman MM, Harding CV. 2013. Interferon-alpha is the primary plasma type-I IFN in HIV-1 infection and correlates with immune activation and disease markers. PLoS One 8:e56527.
    123.
    Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS. 1997. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A 94:13193–13197.
    124.
    Henderson S, Rowe M, Gregory C, Croom-Carter D, Wang F, Longnecker R, Kieff E, Rickinson A. 1991. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell 65:1107–1115.
    125.
    Poole E, McGregor Dallas SR, Colston J, Joseph RS, Sinclair J. 2011. Virally induced changes in cellular microRNAs maintain latency of human cytomegalovirus in CD34(+) progenitors. J Gen Virol 92:1539–1549.
    126.
    Kim Y, Anderson JL, Lewin SR. 2018. Getting the “kill” into “shock and kill”: strategies to eliminate latent HIV. Cell Host Microbe 23:14–26.
    127.
    Lee GQ, Orlova-Fink N, Einkauf K, Chowdhury FZ, Sun X, Harrington S, Kuo H-H, Hua S, Chen H-R, Ouyang Z, Reddy K, Dong K, Ndung'u T, Walker BD, Rosenberg ES, Yu XG, Lichterfeld M. 2017. Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells. J Clin Invest 127:2689–2696.
    128.
    Hiener B, Horsburgh BA, Eden JS, Barton K, Schlub TE, Lee E, von Stockenstrom S, Odevall L, Milush JM, Liegler T, Sinclair E, Hoh R, Boritz EA, Douek D, Fromentin R, Chomont N, Deeks SG, Hecht FM, Palmer S. 2017. Identification of genetically intact HIV-1 proviruses in specific CD4(+) T cells from effectively treated participants. Cell Rep 21:813–822.
    129.
    Wightman F, Solomon A, Khoury G, Green JA, Gray L, Gorry PR, Ho YS, Saksena NK, Hoy J, Crowe SM, Cameron PU, Lewin SR. 2010. Both CD31+ and CD31 naive CD4+ T cells are persistent HIV type 1-infected reservoirs in individuals receiving antiretroviral therapy. J Infect Dis 202:1738–1748.
    130.
    Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, Boucher G, Boulassel M-R, Ghattas G, Brenchley JM, Schacker TW, Hill BJ, Douek DC, Routy J-P, Haddad EK, Sékaly R-P. 2009. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 15:893–900.
    131.
    Buzon MJ, Sun H, Li C, Shaw A, Seiss K, Ouyang Z, Martin-Gayo E, Leng J, Henrich TJ, Li JZ, Pereyra F, Zurakowski R, Walker BD, Rosenberg ES, Yu XG, Lichterfeld M. 2014. HIV-1 persistence in CD4+ T cells with stem cell-like properties. Nat Med 20:139–142.
    132.
    Jaafoura S, de Goer de Herve MG, Hernandez-Vargas EA, Hendel-Chavez H, Abdoh M, Mateo MC, Krzysiek R, Merad M, Seng R, Tardieu M, Delfraissy JF, Goujard C, Taoufik Y. 2014. Progressive contraction of the latent HIV reservoir around a core of less-differentiated CD4(+) memory T cells. Nat Commun 5:5407.
    133.
    Perreau M, Savoye AL, De Crignis E, Corpataux JM, Cubas R, Haddad EK, De Leval L, Graziosi C, Pantaleo G. 2013. Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J Exp Med 210:143–156.
    134.
    Airo P, Torti C, Uccelli MC, Malacarne F, Palvarini L, Carosi G, Castelli F. 2000. Naive CD4+ T lymphocytes express high levels of Bcl-2 after highly active antiretroviral therapy for HIV infection. AIDS Res Hum Retroviruses 16:1805–1807.
    135.
    Ren YH, Patel S, Magat D, Macedo AB, Durga R, Zale E, Mota T, Truong R, Rohwetter T, McCann CD, Kovacs CC, Benko E, Wimpelberg A, Cannon C, Hardy WD, Bosque A, Bollard CM, Jones RB. 9 May 2019. BCL-2 antagonism sensitizes CTL-resistant HIV reservoirs to elimination ex vivo. SSRN Electronic J doi:
    136.
    Zerbato JM, McMahon DK, Sobolewski MD, Mellors JW, Sluis-Cremer N. 7 February 2019. Naive CD4+ T cells harbor a large inducible reservoir of latent, replication-competent HIV-1. Clin Infect Dis doi:
    137.
    Rocco J, Mellors JW, Macatangay BJ. 2018. Regulatory T cells: the ultimate HIV reservoir? J Virus Erad 4:209–214.
    138.
    Fehervari Z, Sakaguchi S. 2004. CD4+ Tregs and immune control. J Clin Invest 114:1209–1217.
    139.
    Fontenot JD, Gavin MA, Rudensky AY. 2003. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4:330–336.
    140.
    Pandiyan P, Gartner D, Soezeri O, Radbruch A, Schulze-Osthoff K, Brunner-Weinzierl MC. 2004. CD152 (CTLA-4) determines the unequal resistance of Th1 and Th2 cells against activation-induced cell death by a mechanism requiring PI3 kinase function. J Exp Med 199:831–842.
    141.
    McGary CS, Deleage C, Harper J, Micci L, Ribeiro SP, Paganini S, Kuri-Cervantes L, Benne C, Ryan ES, Balderas R, Jean S, Easley K, Marconi V, Silvestri G, Estes JD, Sekaly RP, Paiardini M. 2017. CTLA-4(+)PD-1(−) memory CD4(+) T cells critically contribute to viral persistence in antiretroviral therapy-suppressed, SIV-infected rhesus macaques. Immunity 47:776–788.e5.
    142.
    Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, Almeida JR, Gostick E, Yu Z, Carpenito C, Wang E, Douek DC, Price DA, June CH, Marincola FM, Roederer M, Restifo NP. 2011. A human memory T cell subset with stem cell-like properties. Nat Med 17:1290–1297.
    143.
    Zhang Y, Joe G, Hexner E, Zhu J, Emerson SG. 2005. Host-reactive CD8+ memory stem cells in graft-versus-host disease. Nat Med 11:1299–1305.
    144.
    Chahroudi A, Silvestri G, Lichterfeld M. 2015. T memory stem cells and HIV: a long-term relationship. Curr HIV/AIDS Rep 12:33–40.
    145.
    Walker BD, Yu XG. 2013. Unravelling the mechanisms of durable control of HIV-1. Nat Rev Immunol 13:487–498.
    146.
    Banga R, Procopio FA, Noto A, Pollakis G, Cavassini M, Ohmiti K, Corpataux J-M, de Leval L, Pantaleo G, Perreau M. 2016. PD-1+ and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals. Nat Med 22:754–761.
    147.
    Breton G, Chomont N, Takata H, Fromentin R, Ahlers J, Filali-Mouhim A, Riou C, Boulassel M-R, Routy J-P, Yassine-Diab B, Sékaly R-P. 2013. Programmed death-1 is a marker for abnormal distribution of naive/memory T cell subsets in HIV-1 infection. J Immunol 191:2194–2204.
    148.
    Hakre S, Chavez L, Shirakawa K, Verdin E. 2012. HIV latency: experimental systems and molecular models. FEMS Microbiol Rev 36:706–716.
    149.
    Kondrack RM, Harbertson J, Tan JT, McBreen ME, Surh CD, Bradley LM. 2003. Interleukin 7 regulates the survival and generation of memory CD4 cells. J Exp Med 198:1797–1806.
    150.
    Marini A, Harper JM, Romerio F. 2008. An in vitro system to model the establishment and reactivation of HIV-1 latency. J Immunol 181:7713–7720.
    151.
    Kim M, Hosmane NN, Bullen CK, Capoferri A, Yang HC, Siliciano JD, Siliciano RF. 2014. A primary CD4(+) T cell model of HIV-1 latency established after activation through the T cell receptor and subsequent return to quiescence. Nat Protoc 9:2755–2770.
    152.
    Yang H-C, Xing S, Shan L, O'Connell K, Dinoso J, Shen A, Zhou Y, Shrum CK, Han Y, Liu JO, Zhang H, Margolick JB, Siliciano RF. 2009. Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation. J Clin Invest 119:3473–3486.
    153.
    Sunshine S, Kirchner R, Amr SS, Mansur L, Shakhbatyan R, Kim M, Bosque A, Siliciano RF, Planelles V, Hofmann O, Ho Sui S, Li JZ. 2016. HIV integration site analysis of cellular models of HIV latency with a probe-enriched next-generation sequencing assay. J Virol 90:4511–4519.
    154.
    Saleh S, Solomon A, Wightman F, Xhilaga M, Cameron PU, Lewin SR. 2007. CCR7 ligands CCL19 and CCL21 increase permissiveness of resting memory CD4+ T cells to HIV-1 infection: a novel model of HIV-1 latency. Blood 110:4161–4164.
    155.
    Saleh S, Wightman F, Ramanayake S, Alexander M, Kumar N, Khoury G, Pereira C, Purcell D, Cameron PU, Lewin SR. 2011. Expression and reactivation of HIV in a chemokine induced model of HIV latency in primary resting CD4+ T cells. Retrovirology 8:80.
    156.
    Ziegler E, Oberbarnscheidt M, Bulfone-Paus S, Forster R, Kunzendorf U, Krautwald S. 2007. CCR7 signaling inhibits T cell proliferation. J Immunol 179:6485–6493.
    157.
    Kochetkova M, Kumar S, McColl SR. 2009. Chemokine receptors CXCR4 and CCR7 promote metastasis by preventing anoikis in cancer cells. Cell Death Differ 16:664–673.
    158.
    Wu S, Xing W, Peng J, Yuan X, Zhao X, Lei P, Li W, Wang M, Zhu H, Huang B, Huang L, Shen G. 2008. Tumor transfected with CCL21 enhanced reactivity and apoptosis resistance of human monocyte-derived dendritic cells. Immunobiology 213:417–426.
    159.
    Banas B, Wornle M, Berger T, Nelson PJ, Cohen CD, Kretzler M, Pfirstinger J, Mack M, Lipp M, Grone HJ, Schlondorff D. 2002. Roles of SLC/CCL21 and CCR7 in human kidney for mesangial proliferation, migration, apoptosis, and tissue homeostasis. J Immunol 168:4301–4307.
    160.
    Xu Y, Liu L, Qiu X, Liu Z, Li H, Li Z, Luo W, Wang E. 2012. CCL21/CCR7 prevents apoptosis via the ERK pathway in human non-small cell lung cancer cells. PLoS One 7:e33262.
    161.
    Kim JW, Ferris RL, Whiteside TL. 2005. Chemokine C receptor 7 expression and protection of circulating CD8+ T lymphocytes from apoptosis. Clin Cancer Res 11:7901–7910.
    162.
    Takata H, Kessing C, Sy A, Lima N, Sciumbata J, Mori L, Jones RB, Chomont N, Michael NL, Valente S, Trautmann L. 2019. Modeling HIV-1 latency using primary CD4+ T cells from virally suppressed HIV-1-infected individuals on antiretroviral therapy. J Virol 93:e02248-18.
    163.
    Deeks SG. 2012. HIV: shock and kill. Nature 487:439–440.
    164.
    Ho YC, Shan L, Hosmane NN, Wang J, Laskey SB, Rosenbloom DI, Lai J, Blankson JN, Siliciano JD, Siliciano RF. 2013. Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 155:540–551.
    165.
    Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S, Johnson EF, Marsh KC, Mitten MJ, Nimmer P, Roberts L, Tahir SK, Xiao Y, Yang X, Zhang H, Fesik S, Rosenberg SH, Elmore SW. 2008. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 68:3421–3428.
    166.
    Ashkenazi A, Fairbrother WJ, Leverson JD, Souers AJ. 2017. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nat Rev Drug Discov 16:273–284.
    167.
    Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, Huang DC, Hymowitz SG, Jin S, Khaw SL, Kovar PJ, Lam LT, Lee J, Maecker HL, Marsh KC, Mason KD, Mitten MJ, Nimmer PM, Oleksijew A, Park CH, Park CM, Phillips DC, Roberts AW, Sampath D, Seymour JF, Smith ML, Sullivan GM, Tahir SK, Tse C, Wendt MD, Xiao Y, Xue JC, Zhang H, Humerickhouse RA, Rosenberg SH, Elmore SW. 2013. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 19:202–208.
    168.
    Cummins NW, Sainski-Nguyen AM, Natesampillai S, Aboulnasr F, Kaufmann S, Badley AD. 2017. Maintenance of the HIV reservoir is antagonized by selective BCL2 inhibition. J Virol 91:e00012-17.
    169.
    Huang SH, Ren Y, Thomas AS, Chan D, Mueller S, Ward AR, Patel S, Bollard CM, Cruz CR, Karandish S, Truong R, Macedo AB, Bosque A, Kovacs C, Benko E, Piechocka-Trocha A, Wong H, Jeng E, Nixon DF, Ho YC, Siliciano RF, Walker BD, Jones RB. 2018. Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells. J Clin Invest 128:876–889.
    170.
    Yecies D, Carlson NE, Deng J, Letai A. 2010. Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1. Blood 115:3304–3313.
    171.
    Opydo-Chanek M, Gonzalo O, Marzo I. 2017. Multifaceted anticancer activity of BH3 mimetics: current evidence and future prospects. Biochem Pharmacol 136:12–23.
    172.
    Nakajima W, Sharma K, Hicks MA, Le N, Brown R, Krystal GW, Harada H. 2016. Combination with vorinostat overcomes ABT-263 (navitoclax) resistance of small cell lung cancer. Cancer Biol Ther 17:27–35.
    173.
    Bashiri K, Rezaei N, Nasi M, Cossarizza A. 2018. The role of latency reversal agents in the cure of HIV: a review of current data. Immunol Lett 196:135–139.
    174.
    Archin NM, Kirchherr JL, Sung JA, Clutton G, Sholtis K, Xu Y, Allard B, Stuelke E, Kashuba AD, Kuruc JD, Eron J, Gay CL, Goonetilleke N, Margolis DM. 2017. Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency. J Clin Invest 127:3126–3135.
    175.
    Rasmussen TA, Tolstrup M, Brinkmann CR, Olesen R, Erikstrup C, Solomon A, Winckelmann A, Palmer S, Dinarello C, Buzon M, Lichterfeld M, Lewin SR, Ostergaard L, Sogaard OS. 2014. Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV 1:e13–e21.
    176.
    Schwartz J, Niu X, Walton E, Hurley L, Lin H, Edwards H, Taub JW, Wang Z, Ge Y. 2016. Synergistic anti-leukemic interactions between ABT-199 and panobinostat in acute myeloid leukemia ex vivo. Am J Transl Res 8:3893–3902.
    177.
    Miller LK, Kobayashi Y, Chen CC, Russnak TA, Ron Y, Dougherty JP. 2013. Proteasome inhibitors act as bifunctional antagonists of human immunodeficiency virus type 1 latency and replication. Retrovirology 10:120.
    178.
    Natesampillai S, Cummins NW, Nie Z, Sampath R, Baker JV, Henry K, Pinzone M, O'Doherty U, Polley EC, Bren GD, Katzmann DJ, Badley AD. 2018. HIV protease-generated Casp8p41, when bound and inactivated by BclII, is degraded by the proteasome. J Virol 92:e00037-18.
    179.
    Reuland SN, Goldstein NB, Partyka KA, Smith S, Luo Y, Fujita M, Gonzalez R, Lewis K, Norris DA, Shellman YG. 2012. ABT-737 synergizes with bortezomib to kill melanoma cells. Biol Open 1:92–100.
    180.
    Chauhan D, Tian Z, Zhou B, Kuhn D, Orlowski R, Raje N, Richardson P, Anderson KC. 2011. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res 17:5311–5321.
    181.
    Wan Y, Dai N, Tang Z, Fang H. 2018. Small-molecule Mcl-1 inhibitors: emerging anti-tumor agents. Eur J Med Chem 146:471–482.
    182.
    Leverson JD, Zhang H, Chen J, Tahir SK, Phillips DC, Xue J, Nimmer P, Jin S, Smith M, Xiao Y, Kovar P, Tanaka A, Bruncko M, Sheppard GS, Wang L, Gierke S, Kategaya L, Anderson DJ, Wong C, Eastham-Anderson J, Ludlam MJ, Sampath D, Fairbrother WJ, Wertz I, Rosenberg SH, Tse C, Elmore SW, Souers AJ. 2015. Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Cell Death Dis 6:e1590.

    Author Bios

    Aswath P. Chandrasekar
    Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA
    Aswath P. Chandrasekar, M.B.B.S., is a researcher in the HIV/Immunology laboratory under the Department of Infectious Diseases at the Mayo Clinic in Rochester, MN. Dr. Chandrasekar received his M.B.B.S., with First Class, from the K. S. Hegde Medical Academy, Mangalore, India, and aspires to pursue a career in clinical infectious disease and immunology while maintaining a strong interest in basic science research. His current ongoing projects explore the influence of antiapoptotic proteins in HIV persistence and their effect on cytotoxic activity mediated by immune effectors.
    Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA
    Nathan W. Cummins, M.D., is a Consultant in Infectious Diseases, Chair of Infectious Diseases Research, and Assistant Professor of Medicine at the Mayo Clinic in Rochester, MN. He completed medical training at the University of Kentucky, internal medicine and infectious diseases training at the University of Cincinnati, and transplant infectious diseases training at the Mayo Clinic. He has been an HIV clinician and researcher for over 10 years. He has authored or coauthored >40 peer-reviewed publications and has been awarded Fellowship in the Infectious Diseases Society of America (FIDSA).
    Andrew D. Badley
    Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA
    Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA
    Andrew D. Badley, M.D., is the H. H. Sheikh Khalifa Bin Zayed Al-Nahyan Professor of Infectious Diseases, honoring Dr. W. Wilson, and a Professor of Molecular Medicine at the Mayo Clinic in Rochester, MN. He received his M.D. degree from Dalhousie University in Halifax, Nova Scotia, Canada, in 1990 and completed his internal medicine residency and clinician investigator training in infectious diseases at Mayo Clinic, Rochester, MN. Dr. Badley’s research focus investigates the regulation of cell death and cell survival during infectious diseases, notably, HIV infection, and how understanding these processes can lead to novel therapeutic strategies to reduce morbidity and mortality and contribute to a cure of HIV infection. Dr. Badley is a past Associate Dean of Research and currently serves as the Founder and Director of the Office of Translation to Practice and Chair of Research in the Department of Medicine at Mayo Clinic.

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    Clinical Microbiology Reviews
    Volume 33Number 118 December 2019
    eLocator: e00107-19

    History

    Published online: 30 October 2019

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    KEYWORDS

    1. BCL-2 family
    2. antiapoptosis
    3. apoptosis
    4. human immunodeficiency virus

    Contributors

    Authors

    Aswath P. Chandrasekar
    Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA
    Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA
    Andrew D. Badley
    Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA
    Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA

    Notes

    Address correspondence to Andrew D. Badley, [email protected].

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  • Clinical Microbiology ReviewsArticle
    Performance of Zika Assays in the Context of Toxoplasma gondii, Parvovirus B19, Rubella Virus, and Cytomegalovirus (TORCH) Diagnostic Assays

    Performance of Zika Assays in the Context of Toxoplasma gondii, Parvovirus B19, Rubella Virus, and Cytomegalovirus (TORCH) Diagnostic Assays

    SUMMARY

    Infections during pregnancy that may cause congenital abnormalities have been recognized for decades, but their diagnosis is challenging. This was again illustrated with the emergence of Zika virus (ZIKV), highlighting the inherent difficulties in estimating the extent of pre- and postnatal ZIKV complications because of the difficulties in establishing definitive diagnoses. We reviewed the epidemiology, infection kinetics, and diagnostic methods used for Toxoplasma gondii, parvovirus B19, rubella virus, and cytomegalovirus (TORCH) infections and compared the results with current knowledge of ZIKV diagnostic assays to provide a basis for the inclusion of ZIKV in the TORCH complex evaluations. Similarities between TORCH pathogens and ZIKV support inclusion of ZIKV as an emerging TORCH infection. Our review evaluates the diagnostic performance of various TORCH diagnostic assays for maternal screening, fetal screening, and neonatal screening. We show that the sensitivity, specificity, and positive and negative predictive value of TORCH complex pathogens are widely variable, stressing the importance of confirmatory testing and the need for novel techniques for earlier and accurate diagnosis of maternal and congenital infections. In this context it is also important to acknowledge different needs and access to care for different geographic and resource settings.

    REFERENCES

    1.
    Kindhauser MK, Allen T, Frank V, Santhana R, Dye C. 2016. Zika: the origin and spread of a mosquito-borne virus. Bull World Health Organ 94:675–686.
    2.
    Kleber de Oliveira W, Cortez-Escalante J, De Oliveira WT, do Carmo GM, Henriques CM, Coelho GE, Araújo de França GV. 2016. Increase in reported prevalence of microcephaly in infants born to women living in areas with confirmed Zika virus transmission during the first trimester of pregnancy, Brazil, 2015. MMWR Morb Mortal Wkly Rep 65:242–247.
    3.
    FrançA GVA, Schuler-Faccini L, Oliveira WK, Henriques CMP, Carmo EH, Pedi VD, Nunes ML, Castro MC, Serruya S, Silveira MF, Barros FC, Victora CG. 2016. Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation. Lancet 359:891–897.
    4.
    Baud D, Gubler DJ, Schaub B, Lanteri MC, Musso D. 2017. An update on Zika virus infection. Lancet 390:2099–2109.
    5.
    Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, Pretrick M, Marfel M, Holzbauer S, Dubray C, Guillaumot L, Griggs A, Bel M, Lambert AJ, Laven J, Kosoy O, Panella A, Biggerstaff BJ, Fischer M, Hayes EB. 2009. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med 360:2536–2543.
    6.
    Gourinat A-C, O'Connor O, Calvez E, Goarant C, Dupont-Rouzeyrol M. 2015. Detection of Zika virus in urine. Emerg Infect Dis 21:84–86.
    7.
    Mlakar J, Korva M, Tul N, Popović M, Poljšak-Prijatelj M, Mraz J, Kolenc M, Resman Rus K, Vesnaver Vipotnik T, Fabjan Vodušek V, Vizjak A, Pižem J, Petrovec M, Avšič Županc T. 2016. Zika virus associated with microcephaly. N Engl J Med 374:951–958.
    8.
    Cauchemez S, Besnard M, Bompard P, Dub T, Guillemette-Artur P, Eyrolle-Guignot D, Salje H, Van Kerkhove MD, Abadie V, Garel C, Fontanet A, Mallet HP. 2016. Association between Zika virus and microcephaly in French Polynesia, 2013–15: a retrospective study. Lancet 387:2125–2132.
    9.
    Russo FB, Jungmann P, Beltrão-Braga PC. 2017. Zika infection and the development of neurological defects. Cell Microbiol 19:e12744.
    10.
    Kim K, Shresta S. 2016. Neuroteratogenic viruses and lessons for Zika virus models. Trends Microbiol 24:622–636.
    11.
    Da Silva SR, Gao S-J. 2016. Zika virus: an update on epidemiology, pathology, molecular biology and animal model. J Med Virol 88:1291–1296.
    12.
    Van den Pol AN, Mao G, Yang Y, Ornaghi S, Davis JN. 2017. Zika virus targeting in the developing brain. J Neurosci 37:2161–2175.
    13.
    Koide F, Goebel S, Snyder B, Walters KB, Gast A, Hagelin K, Kalkeri R, Rayner J. 2016. Development of a Zika virus infection model in cynomolgus macaques. Front Microbiol 7:2028.
    14.
    Panchaud A, Stojanov M, Ammerdorffer A, Vouga M, Baud D. 2016. Emerging role of Zika virus in adverse fetal and neonatal outcomes. Clin Microbiol Rev 29:659–694.
    15.
    Coelho AVC, Crovella S. 2017. Microcephaly prevalence in infants born to Zika virus-infected women: a systematic review and meta-analysis. Int J Mol Sci 18:E1714.
    16.
    Shapiro-Mendoza CK, Rice ME, Galang RR, Fulton AC, VanMaldeghem K, Prado MV, Ellis E, Anesi MS, Simeone RM, Petersen EE, Ellington SR, Jones AM, Williams T, Reagan-Steiner S, Perez-Padilla J, Deseda CC, Beron A, Tufa AJ, Rosinger A, Roth NM, Green C, Martin S, Lopez CD, deWilde L, Goodwin M, Pagano HP, Mai CT, Gould C, Zaki S, Ferrer LN, Davis MS, Lathrop E, Polen K, Cragan JD, Reynolds M, Newsome KB, Huertas MM, Bhatangar J, Quiñones AM, Nahabedian JF, Adams L, Sharp TM, Hancock WT, Rasmussen SA, Moore CA, Jamieson DJ, Munoz-Jordan JL, Garstang H, Kambui A, Masao C, Honein MA, Meaney-Delman D, Zika Pregnancy and Infant Registries Working Group. 2017. Pregnancy outcomes after maternal Zika virus infection during pregnancy—U.S. Territories, January 1, 2016–April 25, 2017. MMWR Morb Mortal Wkly Rep 66:615–621.
    17.
    Hoen B, Schaub B, Funk AL, Ardillon V, Boullard M, Cabié A, Callier C, Carles G, Cassadou S, Césaire R, Douine M, Herrmann-Storck C, Kadhel P, Laouénan C, Madec Y, Monthieux A, Nacher M, Najioullah F, Rousset D, Ryan C, Schepers K, Stegmann-Planchard S, Tressières B, Voluménie J-L, Yassinguezo S, Janky E, Fontanet A. 2018. Pregnancy outcomes after ZIKV infection in French Territories in the Americas. N Engl J Med 378:985–994.
    18.
    Morris JK, Springett AL, Greenlees R, Loane M, Addor M-C, Arriola L, Barisic I, Bergman JEH, Csaky-Szunyogh M, Dias C, Draper ES, Garne E, Gatt M, Khoshnood B, Klungsoyr K, Lynch C, McDonnell R, Nelen V, Neville AJ, O'Mahony M, Pierini A, Queisser-Luft A, Randrianaivo H, Rankin J, Rissmann A, Kurinczuk J, Tucker D, Verellen-Dumoulin C, Wellesley D, Dolk H. 2018. Trends in congenital anomalies in Europe from 1980 to 2012. PLoS One 13:e0194986.
    19.
    Paz-Bailey G, Rosenberg ES, Doyle K, Munoz-Jordan J, Santiago GA, Klein L, Perez-Padilla J, Medina FA, Waterman SH, Gubern CG, Alvarado LI, Sharp TM. 2018. Persistence of Zika virus in body fluids—final report. N Engl J Med 379:1234–1243.
    20.
    Meaney-Delman D, Oduyebo T, Polen KN, White JL, Bingham AM, Slavinski SA, Heberlein-Larson L, St George K, Rakeman JL, Hills S, Olson CK, Adamski A, Culver Barlow L, Lee EH, Likos AM, Munoz JL, Petersen EE, Dufort EM, Dean AB, Cortese MM, Santiago GA, Bhatnagar J, Powers AM, Zaki S, Petersen LR, Jamieson DJ, Honein MA. 2016. Prolonged detection of Zika virus RNA in pregnant women. Obstet Gynecol 128:724–730.
    21.
    Schaub B, Vouga M, Najioullah F, Gueneret M, Monthieux A, Harte C, Muller F, Jolivet E, Adenet C, Dreux S, Leparc-Goffart I, Cesaire R, Volumenie J-L, Baud D. 2017. Analysis of blood from Zika virus-infected fetuses: a prospective case series. Lancet Infect Dis 17:520–527.
    22.
    Nahmias AJ, Walls KW, Stewart JA, Herrmann KL, Flynt WJ, Jr. 1971. The ToRCH complex-perinatal infections associated with toxoplasma and rubella, cytomegol- and herpes simplex viruses. Pediatr Res 5:405–406.
    23.
    Munro SC, Hall B, Whybin LR, Leader L, Robertson P, Maine GT, Rawlinson WD. 2005. Diagnosis of and screening for cytomegalovirus infection in pregnant women. J Clin Microbiol 43:4713–4718.
    24.
    Forner G, Saldan A, Mengoli C, Gussetti N, Palù G, Abate D. 2016. Cytomegalovirus (CMV) enzyme-linked immunosorbent spot assay but not CMV QuantiFERON assay is a novel biomarker to determine risk of congenital CMV infection in pregnant women. J Clin Microbiol 54:2149–2154.
    25.
    Silasi M, Cardenas I, Racicot K, Kwon J-Y, Aldo P, Mor G. 2015. Viral infections during pregnancy. Am J Reprod Immunol 73:199–213.
    26.
    Coyne CB, Lazear HM. 2016. Zika virus—reigniting the TORCH. Nat Rev Microbiol 14:707–715.
    27.
    Pasquini L, Seravalli V, Sisti G, Battaglini C, Nepi F, Pelagalli R, Di Tommaso M. 2016. Prevalence of a positive TORCH and parvovirus B19 screening in pregnancies complicated by polyhydramnios. Prenat Diagn 36:290–293.
    28.
    Naresh A, Simhan H. 2012. Absence of viruses in amniotic fluid of women with PPROM: a case series. J Reprod Immunol 96:79–83.
    29.
    Brkic S, Bogavac MA, Simin N, Hrnjakovic-Cvetkovic I, Milosevic V, Maric D. 2011. Unusual high rate of asymptomatic maternal parvovirus B19 infection associated with severe fetal outcome. J Matern Fetal Neonatal Med 24:647–649.
    30.
    Vossen A. 2014. Virale infecties in de zwangerschap met risico voor het kind. Stand van zaken. Ned Tijdschr Geneeskd 158:A7418.
    31.
    Bollani L, Strocchio L, Stronati M. 2013. Congenital toxoplasmosis. Early Hum Dev 89(Suppl 4):S70–S72.
    32.
    Lamont RF, Sobel JD, Vaisbuch E, Kusanovic JP, Mazaki-Tovi S, Kim SK, Uldbjerg N, Romero R. 2011. Parvovirus B19 infection in human pregnancy. BJOG 118:175–186.
    33.
    Bessières MH, Berrebi A, Cassaing S, Fillaux J, Cambus JP, Berry A, Assouline C, Ayoubi JM, Magnaval JF. 2009. Diagnosis of congenital toxoplasmosis: prenatal and neonatal evaluation of methods used in Toulouse University Hospital and incidence of congenital toxoplasmosis. Mem Inst Oswaldo Cruz 104:389–392.
    34.
    Cordier AG, Vauloup-Fellous C, Grangeot-Keros L, Pinet C, Benachi A, Ayoubi JM, Picone O. 2012. Pitfalls in the diagnosis of congenital rubella syndrome in the first trimester of pregnancy. Prenat Diagn 32:496–497.
    35.
    Sensini A. 2006. Toxoplasma gondii infection in pregnancy- opportunities and pitfalls of serological diagnosis. Clin Microbiol Infect 12:504–512.
    36.
    Bonvicini F, Puccetti C, Salfi NC, Guerra B, Gallinella G, Rizzo N, Zerbini M. 2011. Gestational and fetal outcomes in B19 maternal infection: a problem of diagnosis. J Clin Microbiol 49:3514–3518.
    37.
    Žegarac Ž, Duić Ž, Borovečki A. 2013. Recent parvovirus B19 infection in late pregnancy. Int J Gynaecol Obstet 122:262–263.
    38.
    de Vries JJ, van Zwet EW, Dekker FW, Kroes AC, Verkerk PH, Vossen AC. 2013. The apparent paradox of maternal seropositivity as a risk factor for congenital cytomegalovirus infection: a population-based prediction model. Rev Med Virol 23:241–249.
    39.
    Crane J, Mundle W, Boucoiran I, Maternal Fetal Medicine Committee. 2014. Parvovirus B19 infection in pregnancy. J Obstet Gynaecol Can 36:1107–1116.
    40.
    Saldan A, Forner G, Mengoli C, Gussetti N, Palù G, Abate D. 2017. Testing for cytomegalovirus in pregnancy. J Clin Microbiol 55:693–702.
    41.
    Vauloup-Fellous C, Grangeot-Keros L. 2007. Humoral immune response after primary rubella virus infection and after vaccination. Clin Vaccine Immunol 14:644–647.
    42.
    Weisblum Y, Panet A, Haimov-Kochman R, Wolf DG. 2014. Models of vertical cytomegalovirus (CMV) transmission and pathogenesis. Semin Immunopathol 36:615–625.
    43.
    de Oliveira Azevedo CT, do Brasil PE, Guida L, Lopes Moreira ME. 2016. Performance of polymerase chain reaction analysis of the amniotic fluid of pregnant women for diagnosis of congenital toxoplasmosis: a systematic review and meta-analysis. PLoS One 11:e0149938.
    44.
    Li Z, Yan C, Liu P, Yan R, Feng Z. 2009. Prevalence of serum antibodies to TORCH among women before pregnancy or in the early period of pregnancy in Beijing. Clin Chim Acta 403:212–215.
    45.
    Ribeiro AC, Mutis MS, Fernandes O. 2008. Association of the presence of residual anti-Toxoplasma gondii IgM in pregnant women and their respective family groups in Miracema, Northwest Rio de Janeiro, Brazil. Mem Inst Oswaldo Cruz 103:591–594.
    46.
    Munoz-Zanzi CA, Fry P, Lesina B, Hill D. 2010. Toxoplasma gondii oocyst-specific antibodies and source of infection. Emerg Infect Dis 16:1591–1593.
    47.
    Villena I, Ancelle T, Delmas C, Garcia P, Brezin AP, Thulliez P, Wallon M, King L, Goulet V, Toxosurv Network and National Reference Centre for Toxoplasmosis. 2010. Congenital toxoplasmosis in France in 2007: first results from a national surveillance system. Euro Surveill 15:19600.
    48.
    Kamal AM, Ahmed AK, Abdellatif MZ, Tawfik M, Hassan EE. 2015. Seropositivity of Toxoplasmosis in pregnant women by ELISA at Minia University Hospital, Egypt. Korean J Parasitol 53:605–610.
    49.
    Candotti D, Etiz N, Parsyan A, Allain JP. 2004. Identification and characterization of persistent human erythrovirus infection in blood donor samples. J Virol 78:12169–12178.
    50.
    Emiasegen SE, Nimzing L, Adoga MP, Ohagenyi AY, Lekan R. 2011. Parvovirus B19 antibodies and correlates of infection in pregnant women attending an antenatal clinic in central Nigeria. Mem Inst Oswaldo Cruz 106:227–231.
    51.
    Lamarre V, Gilbert NL, Rousseau C, Gyorkos TW, Fraser WD. 2016. Seroconversion for cytomegalovirus infection in a cohort of pregnant women in Québec, 2010–2013. Epidemiol Infect 144:1701–1709.
    52.
    Zajkowska A, Garkowski A, Czupryna P, Moniuszko A, Król ME, Szamatowicz J, Pancewicz S. 2015. Seroprevalence of parvovirus B19 antibodies among young pregnant women or planning pregnancy, tested for toxoplasmosis. Przegl Epidemiol 69:479–482.
    53.
    Zhou Y, Bian G, Zhou Q, Gao Z, Liao P, Liu Y, He M. 2015. Detection of cytomegalovirus, human parvovirus B19, and herpes simplex virus-1/2 in women with first-trimester spontaneous abortions. J Med Virol 87:1749–1753.
    54.
    Barlinn R, Vainio K, Samdal HH, Nordbø SA, Nøkleby H, Dudman SG. 2014. Susceptibility to cytomegalovirus, parvovirus B19 and age-dependent differences in levels of rubella antibodies among pregnant women. J Med Virol 86:820–826.
    55.
    Karacan M, Batukan M, Cebi Z, Berberoglugil M, Levent S, Kır M, Baksu A, Ozel E, Camlıbel T. 2014. Screening cytomegalovirus, rubella and toxoplasma infections in pregnant women with unknown pre-pregnancy serological status. Arch Gynecol Obstet 290:1115–1120.
    56.
    de Jong EP, Walther FJ, Kroes AC, Oepkes D. 2011. Parvovirus B19 infection in pregnancy: new insights and management. Prenat Diagn 5:419–425.
    57.
    Cannon MJ, Schmid DS, Hyde TB. 2010. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol 20:202–213.
    58.
    Vynnycky E, Adams EJ, Cutts FT, Reef SE, Navar AM, Simons E, Yoshida LM, Brown DW, Jackson C, Strebel PM, Dabbagh AJ. 2016. Using seroprevalence and immunisation coverage data to estimate the global burden of congenital rubella syndrome, 1996–2010: a systematic review. PLoS One 11:e0149160.
    59.
    Zanga J, Mbanzulu MK, Kabasele A-F, Ngatu NR, Wumba DR. 2017. Rubella seroprevalence and real-time PCR detection of RUBV among Congolese pregnant women. BMC Infect Dis 17:250.
    60.
    Mirambo MM, Majigo M, Aboud S, Groß U, Mshana SE. 2015. Serological markers of rubella infection in Africa in the pre vaccination era: a systematic review. BMC Res Notes 8:716.
    61.
    Loconsole D, Metallo A, De Robertis AL, Morea A, Quarto M, Chironna M. 2018. Seroprevalence of dengue virus, West Nile virus, chikungunya virus, and Zika virus in international travelers attending a travel and migration center in 2015–2017, Southern Italy. Vector Borne Zoonotic Dis 18:331–334.
    62.
    Seruyange E, Gahutu JB, Muvunyi CM, Katare S, Ndahindwa V, Sibomana H, Nyamusore J, Rutagarama F, Hannoun C, Norder H, Bergström T. 2018. Seroprevalence of Zika virus and rubella virus IgG among blood donors in Rwanda and in Sweden. J Med Virol 90:1290–1296.
    63.
    Borena W, Hofer T, Stiasny K, Aberle SW, Gaber M, von Laer D, Schennach H. 2017. No molecular or serological evidence of Zikavirus infection among healthy blood donors living in or travelling to regions where Aedes albopictus circulates. PLoS One 12:e0178175.
    64.
    Saba Villarroel PM, Nurtop E, Pastorino B, Roca Y, Drexler JF, Gallian P, Jaenisch T, Leparc-Goffart I, Priet S, Ninove L, de Lamballerie X. 2018. Zika virus epidemiology in Bolivia: a seroprevalence study in volunteer blood donors. PLoS Negl Trop Dis 12:e0006239.
    65.
    Gake B, Vernet MA, Leparc-Goffart I, Drexler JF, Gould EA, Gallian P, de Lamballerie X. 2017. Low seroprevalence of Zika virus in Cameroonian blood donors. Braz J Infect Dis 21:481–483.
    66.
    Aubry M, Teissier A, Huart M, Merceron S, Vanhomwegen J, Roche C, Vial A, Teururai S, Sicard S, Paulous S, Desprès P, Manuguerra JC, Mallet HP, Musso D, Deparis X, Cao-Lormeau VM. 2017. Zika virus seroprevalence, French Polynesia, 2014–2015. Emerg Infect Dis 23:669–672.
    67.
    Netto EM, Moreira-Soto A, Pedroso C, Höser C, Funk S, Kucharski AJ, Rockstroh A, Kümmerer BM, Sampaio GS, Luz E, Vaz SN, Dias JP, Bastos FA, Cabral K, Kistemann T, Ulbert S, de Lamballerie X, Jaenisch T, Brady OJ, Drosten C, Sarno M, Brites C, Drexler JF. 2017. High Zika virus seroprevalence in Salvador, Northeastern Brazil limits the potential for further outbreaks. mBio 8:e01390-17.
    68.
    Hyde TB, Schmid DS, Cannon MJ. 2010. Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV. Rev Med Virol 20:311–326.
    69.
    Revello MG, Tibaldi C, Masuelli G, Frisina V, Sacchi A, Furione M, Arossa A, Spinillo A, Klersy C, Ceccarelli M, Gerna G, Todros T, CCPE Study Group. 2015. Prevention of primary cytomegalovirus infection in pregnancy. EBioMedicine 2:1205–1210.
    70.
    Lazzarotto T, Guerra B, Gabrielli L, Lanari M, Landini MP. 2011. Update on the prevention, diagnosis and management of cytomegalovirus infection during pregnancy. Clin Microbiol Infect 17:1285–1293.
    71.
    Adler SP. 2011. Screening for cytomegalovirus during pregnancy. Infect Dis Obstet Gynecol 2011:942937.
    72.
    Valeur-Jensen AK, Pedersen CB, Westergaard T, Jensen IP, Lebech M, Andersen PK, Aaby P, Pedersen BN, Melbye M. 1999. Risk factors for parvovirus B19 infection in pregnancy. JAMA 281:1099–1105.
    73.
    Mossong J, Hens N, Friederichs V, Davidkin I, Broman M, Litwinska B, Siennicka J, Trzcinska A, van Damme P, Beutels P, Vyse A, Shkedy Z, Aerts M, Massari M, Gabutti G. 2008. Parvovirus B19 infection in five European countries: seroepidemiology, force of infection and maternal risk of infection. Epidemiol Infect 136:1059–1068.
    74.
    Bouthry E, Picone O, Hamdi G, Grangeot-Keros L, Ayoubi JM, Vauloup-Fellous C. 2014. Rubella and pregnancy: diagnosis, management and outcomes. Prenat Diagn 34:1246–1253.
    75.
    Hutton J, Rowan P, Greisinger A, Mouzoon M. 2014. Rubella monitoring in pregnancy as a means for evaluating a possible reemergence of rubella. Am J Obstet Gyn 211:534.e1–e4.
    76.
    Champagne C, Salthouse DG, Paul R, Cao-Lormeau V-M, Roche B, Cazelles B. 2016. Structure in the variability of the basic reproductive number (R0) for Zika epidemics in the Pacific islands. Elife 5:e19874.
    77.
    Shiu C, Starker R, Kwal J, Bartlett M, Crane A, Greissman S, Gunaratne N, Lardy M, Picon M, Rodriguez P, Gonzalez I, Curry CL. 2018. Zika virus testing and outcomes during pregnancy, Florida, USA, 2016. Emerg Infect Dis 24:1–8.
    78.
    Chalouhi GE, Benedetti S, Alby C, Benzina N, Ville Y. 2014. Cause of fetal demise in first-trimester parvovirus infection: anemia, placentitis or myocarditis? Ultrasound Obstet Gynecol 44:618–619.
    79.
    Puccetti C, Contoli M, Bonvicini F, Cervi F, Simonazzi G, Gallinella G, Murano P, Farina A, Guerra B, Zerbini M, Rizzo N. 2012. Parvovirus B19 in pregnancy: possible consequences of vertical transmission. Prenat Diagn 32:897–902.
    80.
    Citil Dogan A, Wayne S, Bauer S, Ogunyemi D, Kulkharni SK, Maulik D, Carpenter CF, Bahado-Singh RO. 2017. The Zika virus and pregnancy: evidence, management and prevention. J Matern Fetal Neonatal Med 30:386–396.
    81.
    Giambi C, Montaño-Remacha C, Celentano LP, Derrough T, National Focal Points for Rubella. 2015. Surveillance of congenital rubella and rubella infections in pregnancy in EU/EEA countries, 2012: current status and future perspective to monitor elimination. Vaccine 33:4929–4937.
    82.
    Landolsi H, Yacoubi MT, Bouslama L, Lahmar A, Trabelsi A, Hmissa S, Aouni M, Korbi S. 2009. Detection of the human parvovirus B19 in nonimmune hydrops fetalis using immunohistochemistry and nested-PCR in formalin-fixed and paraffin-embedded placenta and fetal tissues. Pathol Biol (Paris) 57:e1–e7.
    83.
    Beigi RH, Wiesenfeld HC, Landers DV, Simhan HN. 2008. High rate of severe fetal outcomes associated with maternal parvovirus b19 infection in pregnancy. Infect Dis Obstet Gynecol 2008:524601.
    84.
    Enders M, Weidner A, Zoellner I, Searle K, Enders G. 2004. Fetal morbidity and mortality after acute human parvovirus B19 infection in pregnancy: prospective evaluation of 1018 cases. Prenat Diagn 24:513–518.
    85.
    Lassen J, Jensen AK, Bager P, Pedersen CB, Panum I, Nørgaard-Pedersen B, Aaby P, Wohlfahrt J, Melbye M. 2012. Parvovirus B19 infection in the first trimester of pregnancy and risk of fetal loss: a population-based case-control study. Am J Epidemiol 176:803–807.
    86.
    Sarfraz AA, Samuelsen SO, Bruu AL, Jenum PA, Eskild A. 2009. Maternal human parvovirus B19 infection and the risk of fetal death and low birthweight: a case-control study within 35,940 pregnant women. BJOG 116:1492–1498.
    87.
    Miyakawa M, Yoshino H, Yoshida LM, Vynnycky E, Motomura H, Tho Le H, Thiem VD, Ariyoshi K, Anh DD, Moriuchi H. 2014. Seroprevalence of rubella in the cord blood of pregnant women and congenital rubella incidence in Nha Trang, Vietnam. Vaccine 32:1192–1198.
    88.
    Li JM, Zhang HF, Zhang XQ, Huang GL, Huang HZ, Yu WW. 2015. Genetic mechanism associated with congenital cytomegalovirus infection and analysis of effects of the infection on pregnancy outcome. Genet Mol Res 14:13247–13257.
    89.
    Lipitz S, Yinon Y, Malinger G, Yagel S, Levit L, Hoffman C, Rantzer R, Weisz B. 2013. Risk of cytomegalovirus-associated sequelae in relation to time of infection and findings on prenatal imaging. Ultrasound Obstet Gynecol 41:508–514.
    90.
    Schleiss MR. 2013. Cytomegalovirus in the neonate: immune correlates of infection and protection. Review article. Clin Dev Immunol 2013:501801.
    91.
    Ticconi C, Pietropolli A, Rezza G. 2016. Zika virus infection and pregnancy: what we do and do not know. Path Global Health 110:262–284.
    92.
    Tanimura K, Tairaku S, Morioka I, Ozaki K, Nagamata S, Morizane M, Deguchi M, Ebina Y, Minematsu T, Yamada H. 2017. Universal screening with use of immunoglobulin G avidity for congenital cytomegalovirus infection. Clin Infect Dis 65:1652–1658.
    93.
    Braakenburg AM, Crespi CM, Holland GN, Wu S, Yu F, Rothova A. 2014. Recurrence rates of ocular toxoplasmosis during pregnancy. Am J Ophthalmol 157:767–773.
    94.
    Kaňková S, Sulc J, Křivohlavá R, Kuběna A, Flegr J. 2012. Slower postnatal motor development in infants of mothers with latent toxoplasmosis during the first 18 months of life. Early Hum Dev 88:879–884.
    95.
    Heegaard ED, Brown KE. 2002. Human parvovirus B19. Clin Microbiol Rev 15:485–505.
    96.
    Fornara C, Furione M, Lilleri D, Cane I, Revello MG, Zavattoni M, Gerna G. 2015. Primary human cytomegalovirus infections: kinetics of ELISA-IgG and neutralizing antibody in pauci/asymptomatic pregnant women vs symptomatic non-pregnant subjects. J Clin Virol 64:45–51.
    97.
    Maine GT, Stricker R, Stricker R. 2012. Kinetics of CMV seroconversion in a Swiss pregnant women population. Diagn Microbiol Infect Dis 73:275–277.
    98.
    Armengol C, Cassaing S, Roques-Malecaze C, Chauvin P, Iriart X, Berry A, Fillaux J. 2017. Time before anti-Toxoplasma IgG seroconversion detection by 7 commercial assays in French pregnant women. Diagn Microbiol Infect Dis 87:103–107.
    99.
    Mahmoudi S, Mamishi S, Suo X, Keshavarz H. 2017. Early detection of Toxoplasma gondii infection by using a interferon gamma release assay: a review. Exp Parasitol 172:39–43.
    100.
    Tipples GA. 2011. Rubella diagnostic issues in Canada. J Infect Dis 204(Suppl 2):S659–S663.
    101.
    Enders G, Daiminger A, Bäder U, Exler S, Schimpf Y, Enders M. 2013. The value of CMV IgG avidity and immunoblot for timing the onset of primary CMV infection in pregnancy. J Clin Virol 56:102–107.
    102.
    Revello MG, Gerna G. 2002. Diagnosis and management of human cytomegalovirus infection in the mother, fetus and newborn infant. Clin Microbiol Rev 15:680–715.
    103.
    Pasquier C, Joguet G, Mengelle C, Chapuy-Regaud S, Pavili L, Prisant N, Izopet J, Bujan L, Mansuy JM. 2018. Kinetics of anti-ZIKV antibodies after Zika infection using two commercial enzyme-linked immunoassays. Diagn Microbiol Infect Dis 90:26–30.
    104.
    Lindblom A, Isa A, Norbeck O, Wolf S, Johansson B, Broliden K, Tolfvenstam T. 2005. Slow clearance of human parvovirus B19 viremia following acute infection. Clin Infect Dis 4:1201–1203.
    105.
    Oduyebo T, Polen KD, Walke HT, Reagan-Steiner S, Lathrop E, Rabe IB, Kuhnert-Tallman WL, Martin SW, Walker AT, Gregory CJ, Ades EW, Carroll DS, Rivera M, Perez-Padilla J, Gould C, Nemhauser JB, Ben Beard C, Harcourt JL, Viens L, Johansson M, Ellington SR, Petersen E, Smith LA, Reichard J, Munoz-Jordan J, Beach MJ, Rose DA, Barzilay E, Noonan-Smith M, Jamieson DJ, Zaki SR, Petersen LR, Honein MA, Meaney-Delman D. 2017. Update: interim guidance for health care providers caring for pregnant women with possible Zika virus exposure—United States (including U.S. territories), July 2017. MMWR Morb Mortal Wkly Rep 66:781–793.
    106.
    Khorrami SM, Mokhtari-Azad T, Yavarian J, Nasab GS, Naseri M, Jandaghi NZ. 2015. The etiology of rubella IgM positivity in patients with rubella-like illness in Iran from 2011 to 2013. J Med Virol 87:1846–1852.
    107.
    Wandinger KP, Saschenbrecker S, Steinhagen K, Scheper T, Meyer W, Bartelt U, Enders G. 2011. Diagnosis of recent primary Rubella virus infections: significance of glycoprotein-based IgM serology, IgG avidity and immunoblot analysis. J Virol Methods 174:85–93.
    108.
    van Helden J, Grangeot-Keros L, Vauloup-Fellous C, Vleminckx R, Masset F, Revello MG. 2014. Evaluation of fully automated assays for the detection of rubella IgM and IgG antibodies by the Elecsys immunoassay system. J Virol Methods 199:108.
    109.
    Gussetti N, D'Elia R, Mottola A, Rigoli E. 1990. Natural immunoglobulin M antibodies against Toxoplasma gondii during pregnancy. Am J Obstet Gyn 162:1359–1360.
    110.
    Konishi E. 1987. A pregnant woman with a high level of naturally occurring immunoglobulin M antibodies to Toxoplasma gondii. Am J Obstet Gyn 157:832–833.
    111.
    Prince HE, Lapé-Nixon M. 2014. Role of cytomegalovirus (CMV) IgG avidity testing in diagnosing primary CMV infection during pregnancy. Clin Vaccine Immunol 21:1377–1384.
    112.
    Revello MG, Vauloup-Fellous C, Grangeot-Keros L, van Helden J, Dickstein Y, Lipkin I, Mühlbacher A, Lazzarotto T. 2012. Clinical evaluation of new automated cytomegalovirus IgM and IgG assays for the Elecsys analyzer platform. Eur J Clin Microbiol Infect Dis 31:3331–3339.
    113.
    Gay-Andrieu F, Fricker-Hidalgo H, Sickinger E, Espern A, Brenier-Pinchart MP, Braun HB, Pelloux H. 2009. Comparative evaluation of the ARCHITECT Toxo IgG, IgM, and IgG avidity assays for anti-Toxoplasma antibodies detection in pregnant women sera. Diagn Microbiol Infect Dis 65:279–287.
    114.
    Murat J-B, L'Ollivier C, Fricker Hidalgo H, Franck J, Pelloux H, Piarroux R. 2012. Evaluation of the new Elecsys Toxo IgG avidity assay for toxoplasmosis and new insights into the interpretation of avidity results. Clin Vaccine Immunol 19:1838–1843.
    115.
    Dogan K, Kafkasli A, Kaya C, Cengiz H. 2013. Seroprevalence and seroconversion rates of cytomegalovirus pp65 antigen and cord blood screening of pregnant women in Malatya, Turkey. Eurasian J Med 45:88–91.
    116.
    Nissapatorn V, Suwanrath C, Sawangjaroen N, Ling LY, Chandeying V. 2011. Toxoplasmosis-serological evidence and associated risk factors among pregnant women in southern Thailand. Am J Trop Med Hyg 85:243–247.
    117.
    El Sanousi SM, Osman ZA, Mohmed AB, Al Awfi MS. 2016. Cytomegalovirus infection in a cohort of pregnant women. Am J Infect Control 44:e41–e3.
    118.
    Leruez-Ville M, Ville Y. 2017. Fetal cytomegalovirus infection. Best Pract Res Clin Obstet Gynaecol 38:97–107.
    119.
    Charrel R, Mögling R, Pas S, Papa A, Baronti C, Koopmans M, Zeller H, Leparc-Goffart I, Reusken CB. 2017. Variable sensitivity in molecular detection of Zika virus in European expert laboratories: external quality assessment, November 2016. J Clin Microbiol 55:3219–3226.
    120.
    Enders M, Weidner A, Rosenthal T, Baisch C, Hedman L, Söderlund-Venermo M, Hedman K. 2008. Improved diagnosis of gestational parvovirus B19 infection at the time of nonimmune fetal hydrops. J Infect Dis 197:58–62.
    121.
    Weseslindtner L, Aberle JH, Hedman L, Hedman K. 2017. The chemokine CXCL-10 is a marker of infection stage in individuals with DNAemia due to parvovirus B19. J Infect Dis 215:214–220.
    122.
    Baylis SA, Shah N, Minor PD. 2004. Evaluation of different assays for the detection of parvovirus B19 DNA in human plasma. J Virol Methods 121:7–16.
    123.
    -de Backer MWA, Russcher A, Kroes ACM, Koppelman MHGM, Lanfermeijer M, Zaaijer HL. 2016. Detection of parvovirus B19 in blood: viruses or DNA remnants? J Clin Virol 84:19–23.
    124.
    Tan SK, Sahoo MK, Milligan S, Taylor N, Pinsky BA. 2017. Stability of Zika virus in urine: specimen processing considerations and implications for the detection of RNA targets in urine. J Virol Methods 248:66–70.
    125.
    Bin Dajem SM, Almushait MA. 2012. Detection of Toxoplasma gondii DNA by PCR in blood samples collected from pregnant Saudi women from the Aseer region, Saudi Arabia. Ann Saudi Med 32:507–512.
    126.
    Turcekova L, Spisak F, Dubinsky P, Ostro A. 2012. Molecular diagnosis of Toxoplasma gondii in pregnant women. Bratisl Lek Listy 113:307–310.
    127.
    Revello MG, Furione M, Rognoni V, Arossa A, Gerna G. 2014. Cytomegalovirus DNAemia in pregnant women. J Clin Virol 61:590–592.
    128.
    Simonazzi G, Cervi F, Zavatta A, Pellizzoni L, Guerra B, Mastroroberto M, Morselli-Labate AM, Gabrielli L, Rizzo N, Lazzarotto T. 2017. Congenital cytomegalovirus infection. Prognostic value of maternal DNAemia at amniocentesis. Clin Infect Dis 64:207–210.
    129.
    Zavattoni M, Furione M, Lanzarini P, Arossa A, Rustico M, Tassis B, Piralla A, Baldanti F. 2016. Monitoring of human cytomegalovirus DNAemia during primary infection in transmitter and non-transmitter mothers. J Clin Virol 82:89–93.
    130.
    Eldar-Yedidia Y, Bar-Meir M, Hillel M, Abitbol G, Broide E, Falk R, Assous M, Schlesinger Y. 2016. Low interferon relative response to cytomegalovirus is associated with low likelihood of intrauterine transmission of the virus. PLoS One 11:e0147883.
    131.
    Ding ZY, Xu F, Chen DZ, Meng XN, Xu TS, Lu MD, Zhuge HX. 2015. A multifactorial analysis of the pregnancy outcomes in cytomegalovirus-infected women. Gynecol Obstet Invest 80:106–112.
    132.
    Wujcicka W, Wilczyński J, Nowakowska D. 2014. Do the placental barrier, parasite genotype and Toll-like receptor polymorphisms contribute to the course of primary infection with various Toxoplasma gondii genotypes in pregnant women? Eur J Clin Microbiol Infect Dis 33:703–709.
    133.
    Curti SP, Figueiredo CA, de Oliveira MI, Andrade JQ, Zugaib M, Frugis Yu AL, Oliveira DB, Durigon EL. 2013. Molecular epidemiology of rubella viruses involved in congenital rubella infections in São Paulo, Brazil, between 1996 and 2009. J Med Virol 85:2034–2041.
    134.
    Ferreira IMR, Vidal JE, de Mattos C. d C B, de Mattos LC, Qu D, Su C, Pereira-Chioccola VL. 2011. Toxoplasma gondii isolates: multilocus RFLP-PCR genotyping from human patients in Sao Paulo State, Brazil identified distinct genotypes. Exp Parasitol 129:190–195.
    135.
    Lilleri D, Zelini P, Fornara C, Comolli G, Revello MG, Gerna G. 2009. Human cytomegalovirus-specific CD4+ and CD8+ T cell responses in primary infection of the immunocompetent and the immunocompromised host. Clin Immunol 131:395–403.
    136.
    Halai UA, Nielsen-Saines K, Moreira ML, de Sequeira PC, Junior J, de Araujo Zin A, Cherry J, Gabaglia CR, Gaw SL, Adachi K, Tsui I, Pilotto JH, Nogueira RR, de Filippis A, Brasil P. 2017. Maternal Zika virus disease severity, virus load, prior dengue antibodies, and their relationship to birth outcomes. Clin Infect Dis 65:877–883.
    137.
    Zhu Z, Xu W, Abernathy ES, Chen MH, Zheng Q, Wang T, Zhang Z, Li C, Wang C, He W, Zhou S, Icenogle J. 2007. Comparison of four methods using throat swabs to confirm rubella virus infection. J Clin Microbiol 45:2847–2852.
    138.
    Okamoto K, Fujii K, Komase K. 2010. Development of a novel TaqMan real-time PCR assay for detecting rubella virus RNA. J Virol Methods 168:267–271.
    139.
    Lustig Y, Cotar AI, Ceianu CS, Castilletti C, Zelena H, Burdino E, van Tienen C, Avsic T, Aarons E, Reusken C. 2018. Lack of Zika virus antibody response in confirmed patients in non-endemic countries. J Clin Virol 99–100:31–34.
    140.
    Toppinen M, Norja P, Aaltonen L-M, Wessberg S, Hedman L, Söderlund-Venermo M, Hedman K. 2015. A new quantitative PCR for human parvovirus B19 genotypes. J Virol Methods 218:40–45.
    141.
    Abo H, Okamoto K, Anraku M, Otsuki N, Sakata M, Icenogle J, Zheng Q, Kurata T, Kase T, Komase K, Takeda M, Mori Y. 2014. Development of an improved RT-LAMP assay for detection of currently circulating rubella viruses. J Virol Methods 207:73–77.
    142.
    Tran DN, Pham NT, Tran TT, Khamrin P, Thongprachum A, Komase K, Hayakawa S, Mizuguchi M, Ushijima H. 2012. Phylogenetic analysis of rubella viruses in Vietnam during 2009–2010. J Med Virol 84:705–710.
    143.
    Rodrigues JP, Andrade HF. Jr, 2015. Efficient duplex solid-phase fluorescent assay (dFISA) for the simultaneous detection of specific anti-T. gondii IgG and IgM due to refined conjugates. J Immunol Methods 420:11–17.
    144.
    De Carolis S, Santucci S, Botta A, Salvi S, Degennaro VA, Garufi C, Garofalo S, Ferrazzani S, Scambia G. 2012. The relationship between TORCH complex false positivity and obstetric outcome in patients with antiphospholipid syndrome. Lupus 21:773–775.
    145.
    Yoshida M, Matsuda H, Yoshinaga Y, Asai K, Kawashima A, Sei K, Furuya K. 2013. Can measurement of maternal anti-cytomegalovirus immunoglobulin-M antibody levels be used to screen for cytomegalovirus infection in embryos and fetuses? J Obstet Gynaecol Res 39:166–169.
    146.
    Bredl S, Plentz A, Wenzel JJ, Pfister H, Möst J, Modrow S. 2011. False-negative serology in patients with acute parvovirus B19 infection. J Clin Virol 51:115–120.
    147.
    Kadkhoda K, Gretchen A, Racano A. 2017. Evaluation of a commercially available Zika virus IgM ELISA: specificity in focus. Diagn Microbiol Infect Dis 88:233–235.
    148.
    Bal TA, Armstrong G, Han XY. 2012. Evaluation of the IMMULITE 2000 CMV IgM assay. Herpesviridae 3:2.
    149.
    Medici MC, Martinelli M, Albonetti V, Chezzi C, Dettori G. 2008. Evaluation of rubella virus immunoglobulin G (IgG) and IgM assays with the new Vidia instrument. J Clin Microbiol 46:1847–1849.
    150.
    Golkar M, Azadmanesh K, Khalili G, Khoshkholgh-Sima B, Babaie J, Mercier C, Brenier-Pinchart MP, Fricker-Hidalgo H, Pelloux H, Cesbron-Delauw MF. 2008. Serodiagnosis of recently acquired Toxoplasma gondii infection in pregnant women using enzyme-linked immunosorbent assays with a recombinant dense granule GRA6 protein. Diagn Microbiol Infect Dis 61:31–39.
    151.
    Hamkar R, Jalilvand S, Abdolbaghi MH, Jelyani KN, Esteghamati A, Hagh-Goo A, Mohktari-Azad T, Nategh R. 2009. Distinguishing between primary infection and reinfection with rubella vaccine virus by IgG avidity assay in pregnant women. East Mediterr Health J 15:94–103.
    152.
    Lutsenko MT, Andrievskaya IA. 2014. Activity of histidine in peripheral blood erythrocytes of pregnant women during exacerbation of cytomegalovirus infection. Bull Exp Biol Med 157:765–768.
    153.
    Alver O, Göral G, Ercan İ. 2014. Investigation of serological results of patients with suspected toxoplasmosis admitted to the ELISA laboratory of Uludağ University Hospital between 2002–2008. Turkiye Parazitol Derg 38:141–146.
    154.
    Yamada H, Nishikawa A, Yamamoto T, Mizue Y, Yamada T, Morizane M, Tairaku S, Nishihira J. 2011. Prospective study of congenital toxoplasmosis screening with use of IgG avidity and multiplex nested PCR methods. J Clin Microbiol 49:2552–2556.
    155.
    Kamel N, Metwally L, Gomaa N, Sayed Ahmed WA, Lotfi M, Younis S. 2014. Primary cytomegalovirus infection in pregnant Egyptian women confirmed by cytomegalovirus IgG avidity testing. Med Princ Pract 23:29–33.
    156.
    Seo S, Cho Y, Park J. 2009. Serologic screening of pregnant Korean women for primary human cytomegalovirus infection using IgG avidity test. Korean J Lab Med 29:557–562.
    157.
    Berger A, Reitter A, Harter PN, Buxmann H, Allwinn R, Louwen F, Doerr HW. 2011. Problems and challenges in the diagnosis of vertical infection with human cytomegalovirus (CMV): lessons from two accidental cases. J Clin Virol 51:285–288.
    158.
    Nozawa N, Fang-Hoover J, Tabata T, Maidji E, Pereira L. 2009. Cytomegalovirus-specific, high-avidity IgG with neutralizing activity in maternal circulation enriched in the fetal bloodstream. J Clin Virol 46(Suppl 4):S58–S63.
    159.
    Kaneko M, Ohhashi M, Minematsu T, Muraoka J, Kusumoto K, Sameshima H. 2017. Maternal immunoglobulin G avidity as a diagnostic tool to identify pregnant women at risk of congenital cytomegalovirus infection. J Infect Chemother 23:173–176.
    160.
    Hashoosh DA, Majeed IA. 2014. Comparison of two assays in the diagnosis of toxoplasmosis: immunological and molecular. East Mediterr Health J 20:46–50.
    161.
    De Paschale M, Agrappi C, Belvisi L, Cagnin D, Cerulli T, Clerici P, Mirri P, Manco MT, Cavallari S, Viganò EF. 2008. Revision of the positive predictive value of IgM anti-Toxoplasma antibodies as an index of recent infection. New Microbiol 31:105–111.
    162.
    Trotta M, Borchi B, Zammarchi L, Sterrantino G, Brogi M, Kiros ST, Lorini C, Bonaccorsi G, Colao MG, Bartoloni A. 2016. Immunoglobulin M indirect fluorescent antibody test for the diagnosis of acute toxoplasmosis during pregnancy in the avidity era. A 14-year experience. J Obstet Gynaecol Res 42:1699–1703.
    163.
    Emelia O, Rahana AR, Mohamad Firdaus A, Cheng HS, Nursyairah MS, Fatinah AS, Azmawati MN, Siti NA, Aisah MY. 2014. IgG avidity assay: a tool for excluding acute toxoplasmosis in prolonged IgM titer sera from pregnant women. Trop Biomed 31:633–640.
    164.
    Findal G, Stray-Pedersen B, Holter EK, Berge T, Jenum PA. 2015. Persistent low Toxoplasma IgG avidity is common in pregnancy: experience from antenatal testing in Norway. PLoS One 10:e0145519.
    165.
    Bobic B, Klun I, Vujanic M, Nikolic A, Ivovic V, Zivkovic T, Djurkovic-Djakovic O. 2009. Comparative evaluation of three commercial Toxoplasma-specific IgG antibody avidity tests and significance in different clinical settings. J Med Microbiol 58:358–364.
    166.
    Sellier Y, Guilleminot T, Ville Y, Leruez-Ville M. 2015. Comparison of the LIAISON CMV IgG Avidity II and the VIDAS CMV IgG Avidity II assays for the diagnosis of primary infection in pregnant women. J Clin Virol 72:46–48.
    167.
    Furione M, Rognoni V, Sarasini A, Zavattoni M, Lilleri D, Gerna G, Revello MG. 2013. Slow increase in IgG avidity correlates with prevention of human cytomegalovirus transmission to the fetus. J Med Virol 85:1960–1967.
    168.
    Ebina Y, Minematsu T, Morioka I, Deguchi M, Tairaku S, Tanimura K, Sonoyama A, Nagamata S, Morizane M, Yamada H. 2015. Rapid increase in the serum cytomegalovirus IgG avidity index in women with a congenitally infected fetus. J Clin Virol 66:44–47.
    169.
    Lazzarotto T, Guerra B, Lanari M, Gabrielli L, Landini MP. 2008. New advances in the diagnosis of congenital cytomegalovirus infection. J Clin Virol 41:192–197.
    170.
    Elyasi H, Babaie J, Fricker-Hidalgo H, Brenier-Pinchart MP, Zare M, Sadeghiani G, Assmar M, Pelloux H, Golkar M. 2010. Use of dense granule antigen GRA6 in an immunoglobulin G avidity test to exclude acute Toxoplasma gondii infection during pregnancy. Clin Vaccine Immunol 17:1349–1355.
    171.
    Smets A, Fauchier T, Michel G, Marty P, Pomares C. 2016. Comparison of Toxoplasma gondii IgG avidity Architect and Vidas assays with the estimated date of infection in pregnant women. Parasite 23:45.
    172.
    Vauloup-Fellous C, Lazzarotto T, Revello MG, Grangeot-Keros L. 2014. Clinical evaluation of the Roche Elecsys CMV IgG Avidity assay. Eur J Clin Microbiol Infect Dis 33:1365–1369.
    173.
    Rajasekariah H, Scott G, Robertson PW, Rawlinson WD. 2013. Improving diagnosis of primary cytomegalovirus infection in pregnant women using immunoblots. J Med Virol 85:315–319.
    174.
    Flori P, Bellete B, Crampe C, Maudry A, Patural H, Chauleur C, Hafid J, Raberin H, Tran Manh Sung R. 2008. A technique for dating toxoplasmosis in pregnancy and comparison with the Vidas anti-toxoplasma IgG avidity test. Clin Microbiol Infect 14:242–249.
    175.
    Khammari I, Saghrouni F, Lakhal S, Bouratbine A, Ben Said M, Boukadida J. 2014. A new IgG immunoblot kit for diagnosis of toxoplasmosis in pregnant women. Korean J Parasitol 52:493–499.
    176.
    Palmer P, Pallier C, Leruez-Ville M, Deplanche M, Morinet F. 1996. Antibody response to human parvovirus B19 in patients with primary infection by immunoblot assay with recombinant proteins. Clin Diagn Lab Immunol 3:236–238.
    177.
    Khammari I, Saghrouni F, Yaacoub A, Gaied Meksi S, Ach H, Garma L, Fathallah A, Ben Saïd M. 2013. IgG western blot for confirmatory diagnosis of equivocal cases of toxoplasmosis by EIA-IgG and fluorescent antibody test. Korean J Parasitol 51:485–488.
    178.
    Eggers M, Radsak K, Enders G, Reschke M. 2001. Use of recombinant glycoprotein antigens gB and gH for diagnosis of primary human cytomegalovirus infection during pregnancy. J Med Virol 63:135–142.
    179.
    Sroka J, Wójcik-Fatla A, Zając V, Sawczyn A, Cisak E, Karamon J, Dutkiewicz J, Bojar I. 2016. Comparison of the efficiency of two commercial kits—ELFA and Western blot in estimating the phase of Toxoplasma gondii infection in pregnant women. Ann Agric Environ Med 23:570–575.
    180.
    L'Ollivier C, Wallon M, Faucher B, Piarroux R, Peyron F, Franck J. 2012. Comparison of mother and child antibodies that target high-molecular-mass Toxoplasma gondii antigens by immunoblotting improves neonatal diagnosis of congenital toxoplasmosis. Clin Vaccine Immunol 19:1326–1328.
    181.
    Vauloup-Fellous C, Berth M, Heskia F, Dugua JM, Grangeot-Keros L. 2013. Re-evaluation of the VIDAS cytomegalovirus (CMV) IgG avidity assay: determination of new cut-off values based on the study of kinetics of CMV-IgG maturation. J Clin Virol 56:118–123.
    182.
    Villard O, Breit L, Cimon B, Franck J, Fricker-Hidalgo H, Godineau N, Houze S, Paris L, Pelloux H, Villena I, Candolfi E, French National Reference Center for Toxoplasmosis Network. 2013. Comparison of four commercially available avidity tests for Toxoplasma gondii-specific IgG antibodies. Clin Vaccine Immunol 20:197–204.
    183.
    Jost C, Touafek F, Fekkar A, Courtin R, Ribeiro M, Mazier D, Paris L. 2011. Utility of immunoblotting for early diagnosis of toxoplasmosis seroconversion in pregnant women. Clin Vaccine Immunol 18:1908–1912.
    184.
    Shan C, Xie X, Ren P, Loeffelholz MJ, Yang Y, Furuya A, Dupuis AP, Kramer LD, Wong SJ, Shi PY. 2017. A rapid Zika diagnostic assay to measure neutralizing antibodies in patients. EBioMed 17:157–162.
    185.
    Revello MG, Genini E, Gorini G, Klersy C, Piralla A, Gerna G. 2010. Comparative evaluation of eight commercial human cytomegalovirus IgG avidity assays. J Clin Virol 48:255–259.
    186.
    Bouthry E, Furione M, Huzly D, Ogee-Nwankwo A, Hao L, Adebayo A, Icenogle J, Sarasini A, Revello MG, Grangeot-Keros L, Vauloup-Fellous C. 2016. Assessing immunity to rubella virus: a plea for standardization of IgG (immuno)assays. J Clin Microbiol 54:1720–1725.
    187.
    Lumley S, Patel M, Griffiths PD. 2014. The combination of specific IgM antibodies and IgG antibodies of low avidity does not always indicate primary infection with cytomegalovirus. J Med Virol 86:834–837.
    188.
    Sickinger E, Gay-Andrieu F, Jonas G, Schultess J, Stieler M, Smith D, Hausmann M, Stricker R, Stricker R, Dhein J, Braun HB. 2008. Performance characteristics of the new ARCHITECT Toxo IgG and Toxo IgG avidity assays. Diagn Microbiol Infect Dis 62:235–244.
    189.
    Sickinger E, Braun HB, Praast G, Stieler M, Gundlach C, Birkenbach C, Prostko J, Palafox MA, Frias E, Hsu S, Matias M, Pucci D, Hausmann M, Sagel U, Smith D. 2009. Evaluation of the Abbott ARCHITECT Toxo IgM assay. Diagn Microbiol Infect Dis 64:275–282.
    190.
    Lagrou K, Bodeus M, Van Ranst M, Goubau P. 2009. Evaluation of the new architect cytomegalovirus immunoglobulin M (IgM), IgG, and IgG avidity assays. J Clin Microbiol 47:1695–1699.
    191.
    Lachaud L, Calas O, Picot MC, Albaba S, Bourgeois N, Pratlong F. 2009. Value of 2 IgG avidity commercial tests used alone or in association to date toxoplasmosis contamination. Diagn Microbiol Infect Dis 64:267–274.
    192.
    Rahbar N, Vali Zadeh S, Ghorbani R, Kheradmand P. 2015. Prevalence of parvovirus B19 specific antibody in pregnant women with spontaneous abortion. Acta Med Iran 53:168–172.
    193.
    Fricker-Hidalgo H, Cimon B, Chemla C, Darde ML, Delhaes L, L'ollivier C, Godineau N, Houze S, Paris L, Quinio D, Robert-Gangneux F, Villard O, Villena I, Candolfi E, Pelloux H. 2013. Toxoplasma seroconversion with negative or transient immunoglobulin M in pregnant women: myth or reality? A French multicenter retrospective study. J Clin Microbiol 51:2103–2111.
    194.
    Carlier P, Harika N, Bailly R, Vranken G. 2010. Laboratory evaluation of the new Access cytomegalovirus immunoglobulin IgM and IgG assays. J Clin Virol 49:192–197.
    195.
    Maudry A, Chene G, Chatelain R, Patural H, Bellete B, Tisseur B, Hafid J, Raberin H, Beretta S, Sung RT, Belot G, Flori P. 2009. Bicentric evaluation of six anti-toxoplasma immunoglobulin G (IgG) automated immunoassays and comparison to the Toxo II IgG Western blot. Clin Vaccine Immunol 16:1322–1326.
    196.
    Gentile M, Galli C, Pagnotti P, Di Marco P, Tzantzoglou S, Bellomi F, Ferreri ML, Selvaggi C, Antonelli G. 2009. Measurement of the sensitivity of different commercial assays in the diagnosis of CMV infection in pregnancy. Eur J Clin Microbiol Infect Dis 28:977–981.
    197.
    Enders M, Helbig S, Hunjet A, Pfister H, Reichhuber C, Motz M. 2007. Comparative evaluation of two commercial enzyme immunoassays for serodiagnosis of human parvovirus B19 infection. J Virol Methods 146:409–413.
    198.
    Ghoneim NH, Shalaby SI, Hassanain NA, Zeedan GS, Soliman YA, Abdalhamed AM. 2010. Comparative study between serological and molecular methods for diagnosis of toxoplasmosis in women and small ruminants in Egypt. Foodborne Pathog Dis 7:17–22.
    199.
    Kasper DC, Prusa AR, Hayde M, Gerstl N, Pollak A, Herkner KR, Reiter-Reisacher R. 2009. Evaluation of the Vitros ECiQ immunodiagnostic system for detection of anti-Toxoplasma immunoglobulin G and immunoglobulin M antibodies for confirmatory testing for acute Toxoplasma gondii infection in pregnant women. J Clin Microbiol 47:164–167.
    200.
    Prusa AR, Hayde M, Unterasinger L, Pollak A, Herkner KR, Kasper DC. 2010. Evaluation of the Roche Elecsys Toxo IgG and IgM electrochemiluminescence immunoassay for the detection of gestational Toxoplasma infection. Diagn Microbiol Infect Dis 68:352–357.
    201.
    Franck J, Garin YJ, Dumon H. 2008. LDBio-Toxo II immunoglobulin G Western blot confirmatory test for anti-toxoplasma antibody detection. J Clin Microbiol 46:2334–2338.
    202.
    Stowe RP, Ruiz RJ, Fagundes CP, Stowe RH, Chen M, Glaser R. 2014. An ELISA method to compute endpoint titers to Epstein-Barr virus and cytomegalovirus: application to population-based studies. J Immunol Methods 408:64–69.
    203.
    Dimech W, Grangeot-Keros L, Vauloup-Fellous C. 2016. Standardization of assays that detect anti-rubella virus IgG antibodies. Clin Microbiol Rev 29:163.
    204.
    Centonze AR, Tonolli E, Fontana R. 2013. Performance characteristics of current-generation Immulite 2000 TORCH Assays. Clin Vaccine Immunol 20:122–126.
    205.
    Murat JB, Dard C, Fricker Hidalgo H, Dardé ML, Brenier-Pinchart MP, Pelloux H. 2013. Comparison of the Vidas system and two recent fully automated assays for diagnosis and follow-up of toxoplasmosis in pregnant women and newborns. Clin Vaccine Immunol 20:1203–1212.
    206.
    Paschale de M, Agrappi M, Manco MT, Clerici P. 2010. Positive predictive value of anti-HCMV IgM as an index of primary infection. J Virol Methods 168:121–125.
    207.
    Drew RJ, Stapleton P, Abu H, Healy E, Ferguson W, De Gascun C, O'Gorman J, Eogan M. 2015. Pregnancy outcomes of mothers with detectable CMV-specific IgM antibodies: a three-year review in a large Irish tertiary referral maternity hospital. Infect Dis Obstet Gynecol 2015:218080.
    208.
    Toriyabe K, Morikawa F, Minematsu T, Ikejiri M, Suga S, Ikeda T. 2017. Anti-cytomegalovirus immunoglobulin M titer for congenital infection in first trimester pregnancy with primary infection: a multicenter prospective cohort study. J Perinatol 37:1272–1277.
    209.
    Tanimura K, Nishikawa A, Tairaku S, Shinozaki N, Deguchi M, Morizane M, Ebina Y, Morioka I, Yamada H. 2015. The IgG avidity value for the prediction of Toxoplasma gondii infection in the amniotic fluid. J Infect Chemother 21:668–671.
    210.
    Enders M, Daiminger A, Exler S, Ertan K, Enders G, Bald R. 2017. Prenatal diagnosis of congenital cytomegalovirus infection in 115 cases- a 5 years’ single center experience. Prenat Diagn 37:389–398.
    211.
    Weiffenbach J, Bald R, Gloning KP, Minderer S, Gärtner BC, Weidner A, Hanke M, Enders M. 2012. Serological and virological analysis of maternal and fetal blood samples in prenatal human parvovirus b19 infection. J Infect Dis 205:782–788.
    212.
    Stajner T, Bobic B, Klun I, Nikolic A, Srbljanovic J, Uzelac A, Rajnpreht I, Djurkovic-Djakovic O. 2016. Prenatal and early postnatal diagnosis of congenital toxoplasmosis in a setting with no systematic screening in pregnancy. Medicine (Baltimore) 95:e2979.
    213.
    Bonvicini F, Manaresi E, Gallinella G, Gentilomi GA, Musiani M, Zerbini M. 2009. Diagnosis of fetal parvovirus B19 infection: value of virological assays in fetal specimens. BJOG 116:813–817.
    214.
    Van Le S, Le DH, Hoang HT, Hoang H, Nguyen NT, Chu HH. 2015. Characterization of rubella virus genotypes among pregnant women in northern Vietnam, 2011–2013. J Med Virol 87:338–343.
    215.
    Fabbri E, Revello MG, Furione M, Zavattoni M, Lilleri D, Tassis B, Quarenghi A, Rustico M, Nicolini U, Ferrazzi E, Gerna G. 2011. Prognostic markers of symptomatic congenital human cytomegalovirus infection in fetal blood. BJOG 118:448–456.
    216.
    Ishikawa A, Yoto Y, Asakura H, Tsutsumi H. 2015. Quantitative analysis of human parvovirus B19 DNA in maternal and fetal serum, and amniotic fluid during an early stage of pregnancy. J Med Virol 87:683–685.
    217.
    Chen CP, Su YN, Chern SR, Wang TY, Tsai FJ, Lin HH, Wu PC, Wang W. 2010. Detection and comparison of cytomegalovirus DNA levels in amniotic fluid and fetal ascites in a second-trimester fetus with massive ascites, hyperechogenic bowel, ventriculomegaly and intrauterine growth restriction. Taiwan J Obstet Gyn 49:206–210.
    218.
    Yamamoto L, Targa LS, Sumita LM, Shimokawa PT, Rodrigues JC, Kanunfre KA, Okay TS. 2017. Association of parasite load levels in amniotic fluid with clinical outcome in congenital toxoplasmosis. Obstet Gynecol 130:335–345.
    219.
    Hsu ST, Chen YT, Huang YF, Yeh TT, Chen WC, Ho ES, Chou MM. 2007. Prenatal diagnosis and perinatal management of maternal-fetal congenital parvovirus B19 infection. Taiwan J Obstet Gyn 46:417–422.
    220.
    Yoshida M, Matsuda H, Yoshinaga Y, Asai K, Kawashima A, Sei K, Horii M, Nakanishi A, Soyama H, Furuya K. 2013. Analysis about the influence on the fetus infected with parvovirus B19 using amniotic erythropoietin and troponin-T. Arch Gynecol Obstet 288:521–525.
    221.
    Schiesser M, Sergi C, Enders M, Maul H, Schnitzler P. 2009. Discordant outcomes in a case of parvovirus b19 transmission into both dichorionic twins. Twin Res Hum Genet 12:175–179.
    222.
    Adams LL, Gungor S, Turan S, Kopelman JN, Harman CR, Baschat AA. 2012. When are amniotic fluid viral PCR studies indicated in prenatal diagnosis? Prenat Diagn 32:88–93.
    223.
    Gervasi MT, Romero R, Bracalente G, Chaiworapongsa T, Erez O, Dong Z, Hassan SS, Yeo L, Yoon BH, Mor G, Barzon L, Franchin E, Militello V, Palù G. 2012. Viral invasion of the amniotic cavity (VIAC) in the midtrimester of pregnancy. J Matern Fetal Neonatal Med 25:2002–2013.
    224.
    Zavattoni M, Paolucci S, Sarasini A, Tassis B, Rustico M, Quarenghi A, Piralla A, Baldanti F. 2016. Diagnostic and prognostic value of molecular and serological investigation of human parvovirus B19 infection during pregnancy. New Microbiol 39:181–185.
    225.
    Goegebuer T, Van Meensel B, Beuselinck K, Cossey V, Van Ranst M, Hanssens M, Lagrou K. 2009. Clinical predictive value of real-time PCR quantification of human cytomegalovirus DNA in amniotic fluid samples. J Clin Microbiol 47:660–665.
    226.
    Prusa AR, Kasper DC, Pollak A, Olischar M, Gleiss A, Hayde M. 2015. Amniocentesis for the detection of congenital toxoplasmosis: results from the nationwide Austrian prenatal screening program. Clin Microbiol Infect 21:191.e1–e8.
    227.
    Teixeira LE, Kanunfre KA, Shimokawa PT, Targa LS, Rodrigues JC, Domingues W, Yamamoto L, Okay TS. 2013. The performance of four molecular methods for the laboratory diagnosis of congenital toxoplasmosis in amniotic fluid samples. Rev Soc Bras Med Trop 46:584–588.
    228.
    Gratzl R, Hayde M, Kohlhauser C, Hermon M, Burda G, Strobl W, Pollak A. 1998. Follow-up of infants with congenital toxoplasmosis detected by PCR analysis of amniotic fluid. Eur J Clin Microbiol Infect Dis 17:853–858.
    229.
    Desveaux C, Klein J, Leruez-Ville M, Ramirez-Torres A, Lacroix C, Breuil B, Froment C, Bascands JL, Schanstra JP, Ville Y. 2016. Identification of symptomatic fetuses infected with cytomegalovirus using amniotic fluid peptide biomarkers. PLoS Pathog 12:e1005395.
    230.
    Costa JM, Alanio A, Moukoury S, Clairet V, Debruyne M, Poveda JD, Bretagne S. 2013. Direct genotyping of Toxoplasma gondii from amniotic fluids based on B1 gene polymorphism using minisequencing analysis. BMC Infect Dis 13:552.
    231.
    Benjamin I, Fernandez G, Figueira JV, Parpacen L, Urbina MT, Medina R. 2017. Zika virus detected in amniotic fluid and umbilical cord blood in an in vitro fertilization-conceived pregnancy in Venezuela. Fertil Steril 107:1319–1322.
    232.
    Ornoy A, Ergaz Z. 2017. Parvovirus B19 infection during pregnancy and risks to the fetus. Birth Defects Res 109:311–323.
    233.
    Durski KN, Tituli C, Ogaoga D, Musto J, Joshua C, Dofai A, Leydon J, Nilles E. 2016. An outbreak investigation of congenital rubella syndrome in Solomon Islands, 2013. Western Pac Surveill Response J 7:10–13.
    234.
    Olariu TR, Remington JS, Montoya JG. 2014. Polymerase chain reaction in cerebrospinal fluid for the diagnosis of congenital toxoplasmosis. Pediatr Infect Dis J 33:566–570.
    235.
    Revello MG, Zavattoni M, Baldanti F, Sarasini A, Paolucci S, Gerna G. 1999. Diagnostic and prognostic value of human cytomegalovirus load and IgM antibody in blood of congenitally infected newborns. J Clin Virol 14:57–66.
    236.
    Wilson CB, Remington JS, Stagno S, Reynolds DW. 1980. Development of adverse sequelae in children born with subclinical congenital Toxoplasma infection. Pediatrics 66:767–774.
    237.
    Nijman J, de Vries LS, Koopman-Esseboom C, Uiterwaal CS, van Loon AM, Verboon-Maciolek MA. 2012. Postnatally acquired cytomegalovirus infection in preterm infants: a prospective study on risk factors and cranial ultrasound findings. Arch Dis Child Fetal Neonatal ed 97:F259–63.
    238.
    Forner G, Abate D, Mengoli C, Palù G, Gussetti N. 2015. High cytomegalovirus (CMV) DNAemia predicts CMV sequelae in asymptomatic congenitally infected newborns born to women with primary infection during pregnancy. J Infect Dis 212:67–71.
    239.
    Samedi VM, Skappak C, Jantzie L, Trevenen C, Kamaluddeen M, Ekwalanga P, Al Awad EH. 2016. Comparison of presentation, course, and outcome of congenital and acquired cytomegalovirus infection in twins. AJP Rep 6:e1–e5.
    240.
    Pejcic I, Rankovic Janevski M, Knezevic A, Jevtovic D, Stanojevic M. 2016. Rubella immune status of neonates-a window towards seroprevalence among childbearing women. BMC Public Health 16:838.
    241.
    Armstrong L, Isaacs D, Evans N. 2004. Severe neonatal toxoplasmosis after third trimester maternal infection. Pediatr Infect Dis J 23:968–969.
    242.
    Goeyvaerts N, Hens N, Aerts M, Beutels P. 2011. Model structure analysis to estimate basic immunological processes and maternal risk for parvovirus B19. Biostatistics 12:283–302.
    243.
    van den Berg JP, Westerbeek EA, Smits GP, van der Klis FR, Berbers GA, van Elburg RM. 2014. Lower transplacental antibody transport for measles, mumps, rubella and varicella zoster in very preterm infants. PLoS One 9:e94714.
    244.
    Murat J-B, Hidalgo HF, Brenier-Pinchart M-P, Pelloux H. 2013. Human toxoplasmosis: which biological diagnostic tests are best suited to which clinical situations? Expert Rev Anti Infect Ther 11:943–956.
    245.
    Kaneko M, Sameshima H, Minematsu T, Kusumoto K, Yamauchi A, Ikenoue T. 2013. Maternal IgG avidity, IgM and ultrasound abnormalities: combined method to detect congenital cytomegalovirus infection with sequelae. J Perinatol 33:831–835.
    246.
    Marangoni A, Capretti MG, De Angelis M, Nardini P, Compri M, Foschi C, Orlandi A, Marsico C, Righetti F, Faldella G, Cevenini R. 2014. Evaluation of a new protocol for retrospective diagnosis of congenital toxoplasmosis by use of Guthrie cards. J Clin Microbiol 52:2963–2970.
    247.
    Tridapalli E, Capretti MG, Farneti G, Marangoni A, Cevenini R, Faldella G. 2008. Congenital toxoplasmosis: the importance of the western blot method to avoid unnecessary therapy in potentially infected newborns. Acta Paediatr 97:1298–1300.
    248.
    Fonseca ZC, Rodrigues I, Melo N, Avelar JB, Castro AM, Avelino MM. 2017. IgG avidity test in congenital toxoplasmosis diagnoses in newborns. Pathogens 6:26.
    249.
    Chumpitazi BF, Boussaid A, Pelloux H, Racinet C, Bost M, Goullier-Fleuret A. 1995. Diagnosis of congenital toxoplasmosis by immunoblotting and relationship with other methods. J Clin Microbiol 33:1479–1485.
    250.
    Marchant E, Bishop L, Flaxman D, Jagodzinski J, Nanjundappa M, Muniyappa P, Cordery R. 2016. A case of congenital rubella syndrome and infection in South-East London in 2015: prevention, diagnosis, and the public health response. Br J Gen Pract 66:635–636.
    251.
    Thomas HI, Morgan-Capner P, Cradock-Watson JE, Enders G, Best JM, O'Shea S. 1993. Slow maturation of IgG1 avidity and persistence of specific IgM in congenital rubella: implications for diagnosis and immunopathology. J Med Virol 41:196–200.
    252.
    Ligozzi M, Poggi M, Saletti M, Gibellini D. 2016. Development of a real-time quantitative polymerase chain reaction assay for the detection of congenital human cytomegalovirus infection in urine samples. Mol Cell Probes 30:50–52.
    253.
    Sugishita Y, Akiba T, Sumitomo M, Hayata N, Hasegawa M, Tsunoda T, Okazaki T, Murauchi K, Hayashi Y, Kai A, Seki N, Kayebeta A, Iwashita Y, Kurita M, Tahara N. 2016. Shedding of rubella virus among infants with congenital rubella syndrome born in Tokyo, Japan, 2013–2014. Jpn J Infect Dis 69:418–423.
    254.
    Cannon MJ, Hyde TB, Schmid DS. 2011. Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection. Rev Med Virol 21:240–255.
    255.
    Jin L, Thomas B. 2007. Application of molecular and serological assays to case based investigations of rubella and congenital rubella syndrome. J Med Virol 79:1017–1024.
    256.
    Nijman J, Mandemaker FS, Verboon-Maciolek MA, Aitken SC, van Loon AM, de Vries LS, Schuurman R. 2014. Genotype distribution, viral load and clinical characteristics of infants with postnatal or congenital cytomegalovirus infection. PLoS One 9:e108018.
    257.
    Sun XM, Ji YS, Elashram SA, Lu ZM, Liu XY, Suo X, Chen QJ, Wang H. 2012. Identification of antigenic proteins of Toxoplasma gondii RH strain recognized by human immunoglobulin G using immunoproteomics. J Proteomics 77:423–432.
    258.
    Baschirotto PT, Krieger MA, Foti L. 2017. Preliminary multiplex microarray IgG immunoassay for the diagnosis of toxoplasmosis and rubella. Mem Inst Oswaldo Cruz 112:428–436.
    259.
    Wang Y, Hedman L, Perdomo MF, Elfaitouri A, Bölin-Wiener A, Kumar A, Lappalainen M, Söderlund-Venermo M, Blomberg J, Hedman K. 2016. Microsphere-based antibody assays for human parvovirus B19V, CMV and T. gondii. BMC Infect Dis 16:8.
    260.
    Kotresha D, Noordin R. 2010. Recombinant proteins in the diagnosis of toxoplasmosis. APMIS 118:529–542.
    261.
    Dai JF, Jiang M, Qu LL, Sun L, Wang YY, Gong LL, Gong RJ, Si J. 2013. Toxoplasma gondii: enzyme-linked immunosorbent assay based on a recombinant multi-epitope peptide for distinguishing recent from past infection in human. Exp Parasitol 133:95–100.
    262.
    Liu L, Liu T, Yu L, Cai Y, Zhang A, Xu X, Luo Q, Hu Y, Song W, Lun Z, Lu F, Wang Y, Shen J. 2012. rROP2(186–533): a novel peptide antigen for detection of IgM antibodies against Toxoplasma gondii. Foodborne Pathog Dis 9:7–12.
    263.
    Costa JG, Peretti LE, García VS, Peverengo L, González VD, Gugliotta LM, Dalla Fontana ML, Lagier CM, Marcipar IS. 2017. P35 and P22 Toxoplasma gondii antigens abbreviate regions to diagnose acquired toxoplasmosis during pregnancy: toward single-sample assays. Clin Chem Lab Med 55:595–604.
    264.
    Lilleri D, Gerna G, Furione M, Zavattoni M, Spinillo A. 2016. Neutralizing and ELISA IgG antibodies to human cytomegalovirus glycoprotein complexes may help date the onset of primary infection in pregnancy. J Clin Virol 81:16–24.
    265.
    Lilleri D, Kabanova A, Revello MG, Percivalle E, Sarasini A, Genini E, Sallusto F, Lanzavecchia A, Corti D, Gerna G. 2013. Fetal human cytomegalovirus transmission correlates with delayed maternal antibodies to gH/gL/pUL128-130-131 complex during primary infection. PLoS One 8:e59863.
    266.
    Teh AY, Amerizadeh A, Osman S, Yunus MH, Noordin R. 2016. Identification, production and assessment of two Toxoplasma gondii recombinant proteins for use in a Toxoplasma IgG avidity assay. Pathog Glob Health 110:277–286.
    267.
    de Souza Macre M, Pires M, Meireles LR, Angel SO, de Andrade HF, Jr. 2009. Serology using rROP2 antigen in the diagnostic of toxoplasmosis in pregnant women. Rev Inst Med Trop Sao Paulo 51:283–288.
    268.
    Petrova EK, Dmitrieva AA, Trifonova EA, Nikitin NA, Karpova OV. 2016. The key role of rubella virus glycoproteins in the formation of immune response, and perspectives on their use in the development of new recombinant vaccines. Vaccine 34:1006–1011.
    269.
    Ardizzoni A, Capuccini B, Baschieri MC, Orsi CF, Rumpianesi F, Peppoloni S, Cermelli C, Meacci M, Crisanti A, Steensgaard P, Blasi E. 2009. A protein microarray immunoassay for the serological evaluation of the antibody response in vertically transmitted infections. Eur J Clin Microbiol Infect Dis 28:1067–1075.
    270.
    Madi JM, Souza R. d S d, Araújo B. F d, Oliveira Filho P F d, Rombaldi RL, Mitchell C, Lorencetti J, Marcon NO. 2010. Prevalence of toxoplasmosis, HIV, syphilis and rubella in a population of puerperal women using Whatman 903 filter paper. Braz J Infect Dis 14:24–29.
    271.
    Cañedo-Solares I, Ortiz-Alegría LB, Figueroa-Damián R, Bustos-Bahena ML, González-Henkel H, Calderón-Segura E, Luna-Pastén H, Correa D. 2009. Toxoplasmosis in pregnancy: determination of IgM, IgG and avidity in filter paper-embedded blood. J Perinatol 29:668–672.
    272.
    Boa-Sorte N, Purificação A, Amorim T, Assunção L, Reis A, Galvão-Castro B. 2014. Dried blood spot testing for the antenatal screening of HTLV, HIV, syphilis, toxoplasmosis and hepatitis B and C: prevalence, accuracy and operational aspects. Braz J Infect Dis 18:618–624.
    273.
    Augustine S. 2016. Towards universal screening for toxoplasmosis- rapid, cost-effective, and simultaneous detection of anti-toxoplasma IgG, IgM, and IgA antibodies by use of very small serum volumes. J Clin Microbiol 54:1684–1685.
    274.
    Li X, Pomares C, Gonfrier G, Koh B, Zhu S, Gong M, Montoya JG, Dai H. 2016. Multiplexed anti-toxoplasma IgG, IgM, and IgA assay on plasmonic gold chips: towards making mass screening possible with dye test precision. J Clin Microbiol 54:1726–1733.
    275.
    Pomares C, Zhang B, Arulkumar S, Gonfrier G, Marty P, Zhao S, Cheng S, Tang M, Dai H, Montoya JG. 2017. Validation of IgG, IgM multiplex plasmonic gold platform in French clinical cohorts for the serodiagnosis and follow-up of Toxoplasma gondii infection. Diagn Microbiol Infect Dis 87:213–218.
    276.
    Fornara C, Cassaniti I, Zavattoni M, Furione M, Adzasehoun KMG, De Silvestri A, Comolli G, Baldanti F. 2017. Human cytomegalovirus-specific memory CD4+ T-cell response and its correlation with virus transmission to the fetus in pregnant women with primary infection. Clin Infect Dis 65:1659–1665.
    277.
    Mele F, Fornara C, Jarrossay D, Furione M, Arossa A, Spinillo A, Lanzavecchia A, Gerna G, Sallusto F, Lilleri D. 2017. Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy: IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission. PLoS One 12:e0187731.
    278.
    Lilleri D, Fornara C, Revello MG, Gerna G. 2008. Human cytomegalovirus-specific memory CD8+ and CD4+ T cell differentiation after primary infection. J Infect Dis 198:536–543.
    279.
    Fornara C, Lilleri D, Revello MG, Furione M, Zavattoni M, Lenta E, Gerna G. 2011. Kinetics of effector functions and phenotype of virus-specific and γδ T lymphocytes in primary human cytomegalovirus infection during pregnancy. J Clin Immunol 31:1054–1064.
    280.
    Fornara C, Furione M, Arossa A, Gerna G, Lilleri D. 2016. Comparative magnitude and kinetics of human cytomegalovirus-specific CD4+ and CD8+ T-cell responses in pregnant women with primary versus remote infection and in transmitting versus non-transmitting mothers: its utility for dating primary infection in pregnancy. J Med Virol 88:1238–1246.
    281.
    Saldan A, Forner G, Mengoli C, Gussetti N, Palù G, Abate D. 2015. Strong cell mediated immune response to human cytomegalovirus is associated with increased risk of fetal infection in primarily infected pregnant women. Clin Infect Dis 61:1228–1234.
    282.
    Saldan A, Forner G, Mengoli C, Tinto D, Fallico L, Peracchi M, Gussetti N, Palù G, Abate D. 2016. Comparison of the cytomegalovirus (CMV) enzyme-linked immunosorbent spot and CMV QuantiFERON cell-mediated immune assays in CMV-seropositive and -seronegative pregnant and nonpregnant women. J Clin Microbiol 54:1352–1356.
    283.
    Wang X, Li X, Hu S, Qu H, Zhang Y, Ni H, Wang X. 2015. Rapid detection of active human cytomegalovirus infection in pregnancy using loop-mediated isothermal amplification. Mol Med Rep 12:2269–2274.
    284.
    Ng AH, Lee M, Choi K, Fischer AT, Robinson JM, Wheeler AR. 2015. Digital microfluidic platform for the detection of rubella infection and immunity: a proof of concept. Clin Chem 61:420–429.
    285.
    Fernández-Carballo BL, McBeth C, McGuiness I, Kalashnikov M, Baum C, Borrós S, Sharon A, Sauer-Budge AF. 2018. Continuous-flow, microfluidic, qRT-PCR system for RNA virus detection. Anal Bioanal Chem 410:33–43.
    286.
    Kaushik A, Tiwari S, Jayant RD, Vashist A, Nikkhah-Moshaie R, El-Hage N, Nair M. 2017. Electrochemical biosensors for early stage Zika diagnostics. Trends Biotechnol 35:308–317.
    287.
    Song J, Liu C, Mauk MG, Rankin SC, Lok JB, Greenberg RM, Bau HH. 2017. Two-stage isothermal enzymatic amplification for concurrent multiplex molecular detection. Clin Chem 63:714–722.
    288.
    Calvert AE, Biggerstaff BJ, Tanner NA, Lauterbach M, Lanciotti RS. 2017. Rapid colorimetric detection of Zika virus from serum and urine specimens by reverse transcription loop-mediated isothermal amplification (RT-LAMP). PLoS One 12:e0185340.
    289.
    Barberini L, Noto A, Saba L, Palmas F, Fanos V, Dessì A, Zavattoni M, Fattuoni C, Mussap M. 2016. Multivariate data validation for investigating primary HCMV infection in pregnancy. Data Brief 9:220–230.
    290.
    Fattuoni C, Palmas F, Noto A, Barberini L, Mussap M, Grapov D, Dessì A, Casu M, Casanova A, Furione M, Arossa A, Spinillo A, Baldanti F, Fanos V, Zavattoni M. 2016. Primary HCMV infection in pregnancy from classic data towards metabolomics. An exploratory analysis. Clin Chim Acta 460:23–32.
    291.
    Scott GM, Chow SS, Craig ME, Pang CN, Hall B, Wilkins MR, Jones CA, Lloyd AR, Rawlinson WD. 2012. Cytomegalovirus infection during pregnancy with maternofetal transmission induces a proinflammatory cytokine bias in placenta and amniotic fluid. J Infect Dis 205:1305–1310.
    292.
    Geyer H, Bauer M, Neumann J, Lüdde A, Rennert P, Friedrich N, Claus C, Perelygina L, Mankertz A. 2016. Gene expression profiling of rubella virus infected primary endothelial cells of fetal and adult origin. Virol J 13:21.
    293.
    Wataganara T, Bianchi DW. 2004. Fetal cell-free nucleic acids in the maternal circulation. Ann N Y Acad Sci 1022:90–99.
    294.
    Sifakis S, Koukou Z, Spandidos DA. 2015. Cell-free fetal DNA and pregnancy-related complications (review). Mol Med Rep 11:2367–2372.
    295.
    Hui L, Tong S, Uhevaha T, U-Lino K, Hannan NJ. 2016. A comparison of sample collection methods for quantifying cell-free fetal neurodevelopment transcripts in amniotic fluid. BMC Res Notes 9:335.
    296.
    Pardee K, Green AA, Takahashi MK, Braff D, Lambert G, Lee JW, Ferrante T, Ma D, Donghia N, Fan M, Daringer NM, Bosch I, Dudley DM, O'Connor DH, Gehrke L, Collins JJ. 2016. Rapid, low-cost detection of Zika virus using programmable biomolecular components. Cell 165:1255–1266.
    297.
    Tomasoni LR, Meroni V, Bonfanti C, Bollani L, Lanzarini P, Frusca T, Castelli F. 2014. Multidisciplinary approach to congenital Toxoplasma infection: an Italian nationwide survey. New Microbiol 37:347–354.
    298.
    Messedi E, Fki-Berrajah L, Gargouri S, Chouikha A, Chaari A, Bouaziz M, Jallouli H, Yahia AB, Hammami A, Triki H, Karray-Hakim H. 2014. Clinical epidemiological and molecular aspects of rubella outbreak with high number of neurological cases, Tunisia 2011–2012. J Clin Virol 61:248–254.
    299.
    Lilleri D, Gerna G. 2017. Maternal immune correlates of protection from human cytomegalovirus transmission to the fetus after primary infection in pregnancy. Rev Med Virol 27:e1921.
    300.
    Frischknecht F, Sell W, Trummer I, Brühwiler H. 2011. Serological testing for infectious diseases in pregnant women: are the guidelines followed? Swiss Med Wkly 140:w13138.
    301.
    Cordeiro MT, Brito CA, Pena LJ, Castanha PM, Gil LH, Lopes KG, Dhalia R, Meneses JA, Ishigami AC, Mello LM, Alencar LX, Guarines KM, Rodrigues LC, Marques ET. 2016. Results of a Zika virus (ZIKV) immunoglobulin M-specific diagnostic assay are highly correlated with detection of neutralizing anti-ZIKV antibodies in neonates with congenital disease. J Infect Dis 214:1897–1904.
    302.
    Binnicker MJ, Jespersen DJ, Harring JA. 2010. Multiplex detection of IgM and IgG class antibodies to Toxoplasma gondii, rubella virus, and cytomegalovirus using a novel multiplex flow immunoassay. Clin Vaccine Immunol 17:1734–1738.
    303.
    Maple PA, Hedman L, Dhanilall P, Kantola K, Nurmi V, Söderlund-Venermo M, Brown KE, Hedman K. 2014. Identification of past and recent parvovirus B19 infection in immunocompetent individuals by quantitative PCR and enzyme immunoassays: a dual-laboratory study. J Clin Microbiol 52:947–956.
    304.
    Beersma MF, Claas ECJ, Sopaheluakan T, Kroes A. 2005. Parvovirus B19 viral loads in relation to VP1 and VP2 antibody responses in diagnostic blood samples. J Clin Virol 34:71–75.
    305.
    Revello MG, Furione M, Zavattoni M, Tassis B, Nicolini U, Fabbri E, Gerna G. 2008. Human cytomegalovirus (HCMV) DNAemia in the mother at amniocentesis as a risk factor for iatrogenic HCMV infection of the fetus. J Infect Dis 197:593–596.
    306.
    Colombo ET, Estofolete CF, Reis AFN, da Silva NS, Aguiar ML, Cabrera EMS, Dos Santos INP, Costa FR, Cruz L, Rombola PL, Terzian ACB, Nogueira ML. 2017. Clinical laboratory and virological data from suspected ZIKV patients in an endemic arbovirus area. J Clin Virol 96:20–25.
    307.
    Garza-González E, Mendoza-Olazarán S, Roman-Campos R, Téllez-Marroquín R, Saldívar-Rodríguez D, Soria-López JA, Guzman A, Flores-Treviño S, Camacho-Ortiz A. 2017. Rapid spread of an ongoing outbreak of Zika virus disease in pregnant women in a Mexican hospital. Braz J Infect Dis 21:554–555.
    308.
    Ren P, Ortiz DA, Terzian A, Colombo TE, Nogueira ML, Vasilakis N, Loeffelholz MJ. 2017. Evaluation of Aptima Zika virus assay. J Clin Microbiol 55:2198–2203.
    309.
    Santiago GA, Vázquez J, Courtney S, Matías KY, Andersen LE, Colón C, Butler AE, Roulo R, Bowzard J, Villanueva JM, Muñoz-Jordan JL. 2018. Performance of the Trioplex real-time RT-PCR assay for detection of Zika, dengue, and chikungunya viruses. Nature Comm 9:1391.
    310.
    Pabbaraju K, Wong S, Gill K, Fonseca K, Tipples GA, Tellier R. 2016. Simultaneous detection of Zika, Chikungunya and Dengue viruses by multiplex real-time PCR assay. J Clin Virol 83:66–71.
    311.
    Waggoner JJ, Gresh L, Mohamed-Hadley A, Ballesteros G, Davila MJ, Tellez Y, Sahoo MK, Balmaseda A, Harris E, Pinsky BA. 2016. Single-reaction multiplex reverse transcription PCR for detection of Zika, chikungunya, and dengue viruses. Emerg Infect Dis 22:1295–1297.
    312.
    Steinhagen K, Probst C, Radzimski C, Schmidt-Chanasit J, Emmerich P, van Esbroeck M, Schinkel J, Grobusch MP, Goorhuis A, Warnecke JM, Lattwein E, Komorowski L, Deerberg A, Saschenbrecker S, Stöcker W, Schlumberger W. 2016. Serodiagnosis of Zika virus (ZIKV) infections by a novel NS1-based ELISA devoid of cross-reactivity with dengue virus antibodies: a multicohort study of assay performance, 2015 to 2016. Euro Surveill 21:304266.
    313.
    Bingham AM, Cone M, Mock V, Heberlein-Larson L, Stanek D, Blackmore C, Likos A. 2016. Comparison of test results for Zika virus RNA in urine, serum, and saliva specimens from persons with travel-associated Zika virus disease Florida, 2016. MMWR Morb Mortal Wkly Rep 65:475–478.
    314.
    Safronetz D, Sloan A, Stein DR, Mendoza E, Barairo N, Ranadheera C, Scharikow L, Holloway K, Robinson A, Traykova-Andonova M, Makowski K, Dimitrova K, Giles E, Hiebert J, Mogk R, Beddome S, Drebot M. 2017. Evaluation of 5 commercially available Zika virus immunoassays. Emerg Infect Dis 23:1577–1580.
    315.
    L'Huillier AG, Hamid-Allie A, Kristjanson E, Papageorgiou L, Hung S, Wong CF, Stein DR, Olsha R, Goneau LW, Dimitrova K, Drebot M, Safronetz D, Gubbay JB. 2017. Evaluation of Euroimmun anti-Zika virus IgM and IgG enzyme-linked immunosorbent assays for Zika virus serologic testing. J Clin Microbiol 55:2462–2471.
    316.
    Granger D, Hilgart H, Misner L, Christensen J, Bistodeau S, Palm J, Strain AK, Konstantinovski M, Liu D, Tran A, Theel ES. 2017. Serologic testing for Zika virus: comparison of three Zika virus IgM-screening enzyme-linked immunosorbent assays and initial laboratory experiences. J Clin Microbiol 55:2127–2136.
    317.
    Lustig Y, Zelena H, Venturi G, Van Esbroeck M, Rothe C, Perret C, Koren R, Katz-Likvornik S, Mendelson E, Schwartz E. 2017. Sensitivity and kinetics of an NS1-based Zika virus enzyme-linked immunosorbent assay in Zika virus-infected travelers from Israel, the Czech Republic, Italy, Belgium, Germany, and Chile. J Clin Microbiol 55:1894–1901.
    318.
    St George K, Sohi IS, Dufort EM, Dean AB, White JL, Limberger R, Sommer JN, Ostrowski S, Wong SJ, Backenson PB, Kuhles D, Blog D, Taylor J, Hutton B, Zucker HA. 2017. Zika virus testing considerations: lessons learned from the first 80 real-time reverse transcription-PCR-positive cases diagnosed in New York State. J Clin Microbiol 55:535–544.
    319.
    Findal G, Helbig A, Haugen G, Jenum PA, Stray-Pedersen B. 2017. Management of suspected primary Toxoplasma gondii infection in pregnant women in Norway: twenty years of experience of amniocentesis in a low-prevalence population. BMC Pregnancy Childbirth 17:127.
    320.
    Margioula-Siarkou C, Kalogiannidis I, Petousis S, Prapa S, Dagklis T, Mamopoulos A, Prapas N, Rousso D. 2015. Cytomegalovirus, Toxoplasma gondii and rubella vertical transmission rates according to mid-trimester amniocentesis: a retrospective study. Int J Prev Med 6:32.
    321.
    Machado AS, Andrade GMQ, Januario JN, Fernandes MD, Carneiro AC, Carneiro M, Carellos EV, Romanelli RM, Vasconcelos-Santos DV, Vitor RW. 2010. IgG and IgM western blot assay for diagnosis of congenital toxoplasmosis. Mem Inst Oswaldo Cruz 105:757–761.
    322.
    Ross SA, Ahmed A, Palmer AL, Michaels MG, Sánchez PJ, Bernstein DI, Tolan RW, Novak Z, Chowdhury N, Fowler KB, Boppana SB, National Institute on Deafness and Other Communication Disorders CHIMES Study. 2014. Detection of congenital cytomegalovirus infection by real-time polymerase chain reaction analysis of saliva or urine specimens. J Infect Dis 210:1415–1418.

    Author Bios

    Bettie Voordouw
    Erasmus Medical Centre, Department of Viroscience, Rotterdam, The Netherlands
    State Institute of Public Health and Environment, Department of Infectious Disease Diagnostics, Research, and Laboratory Surveillance, Bilthoven, The Netherlands
    Bettie Voordouw, M.D., Ph.D., M.P.H., was trained at Leiden University, the Netherlands. She has worked since 2016 as a medical microbiologist with a focus on clinical virology, vaccinology, and public health microbiology at the National Institute of Public Health and Environment, Bilthoven. There, she is also a project leader for reference laboratories. Furthermore, since 2017 she has been a senior scientist at the Department of Viroscience, Erasmus Medical Centre Rotterdam, with particular interest in emerging (viral) infections and optimizing diagnostic algorithms. She has previous long-term experience in the (international) regulatory field, public health agencies, academia, and scientific committees, leading assessment teams and being responsible for and/or participating in scientific advisory bodies and for clinical, treatment, and vaccine guidelines. Since 2017 she has been the Dutch alternate National Microbiology Focal Point to the European Center for Disease Prevention and Control (ECDC). Since 2019 she has been a member of the board of the National Working Group of Clinical Virology of the Dutch Society of Medical Microbiology.
    Barry Rockx
    Erasmus Medical Centre, Department of Viroscience, Rotterdam, The Netherlands
    Barry Rockx, Ph.D., is Head of the Exotic Viruses working group in the Department of Viroscience, Erasmus Medical Centre, Rotterdam. His main research lines involve studies on the tropism, pathogenesis, and host responses of emerging zoonotic viruses causing hemorrhagic, respiratory, and neurological diseases, including orthohantaviruses and arboviruses in a variety of in vitro and in vivo models. He has authored over 50 peer-reviewed scientific publications and several book chapters and has supervised several postdoctoral fellows and students. He has coordinated several NIH-funded projects and contracts and is currently task leader of projects funded by Horizon 2020 of the European Union and by the Netherlands Organization for Health Research and Development (ZonMw). Fields of expertise include tropism, pathogenesis, and the host responses following emerging virus infection.
    Thomas Jaenisch
    Heidelberg University Hospital, Department for Infectious Diseases, Heidelberg, Germany
    Thomas Jaenisch, M.D. Ph.D., is clinical researcher and infectious disease epidemiologist at Heidelberg University Hospital (UKHD). In his research, he focuses on emerging arboviruses of global importance, notably dengue viruses (DENV) and Zika virus (ZIKV). Until recently, he was also responsible for the parasitology reference laboratory at UKHD. Dr. Jaenisch has coordinated in direct sequence two multicenter observational dengue consortia and is now the work package leader in the ZIKAlliance consortium (funded by the European Commission [EC] Horizon 2020 program), where he coordinates the multicenter cohorts in pregnant women and children in Latin America and the Caribbean. He is also responsible for harmonization and data sharing between different Zika consortia, aiming at a pooled analysis of cohort data between the three EC-funded Zika consortia and, in the context of a WHO-moderated effort, with other Zika maternal cohort studies globally.
    Pieter Fraaij
    Erasmus Medical Centre, Department of Viroscience, Rotterdam, The Netherlands
    Pieter Fraaij is a pediatric infectious disease and immunology consultant and head of the subdepartment of Pediatric Infectious Diseases, Immunology, and Rheumatology at the Sophia Children’s Hospital of the Erasmus University Medical Centre in Rotterdam, The Netherlands. In addition, he is employed at the Department of Viroscience at the same institution as a clinical scientist. This unique combination of professional environments has allowed him to set up and implement translational research studies, initiating and coordinating interactions between the scientific and clinical departments. He obtained his Ph.D. at the Erasmus University Rotterdam in clinical, virological, and immunological aspects of highly active antiretroviral therapy in HIV-1-infected children. His current research focuses on the impact of emerging and reemerging viruses and the effects of childhood growth and development on host-virus interactions.
    Philippe Mayaud
    London School of Hygiene and Tropical Medicine, Department of Clinical Research, London, United Kingdom
    Philippe Mayaud, M.D., M.Sc., is a Professor of Infectious Diseases and Reproductive Health at the London School of Hygiene and Tropical Medicine (Faculty of Infectious and Tropical Diseases) and the Head of the HIV Epidemiology and Intervention Research Programme at the Medical Research Unit/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Research Unit in Uganda, which he joined in 2019. His research focuses on epidemiological, clinical, and intervention aspects of HIV/AIDS and sexually transmitted infections, particularly in sub-Saharan Africa. In addition, he has conducted research projects on arbovirus/Zika epidemiology research in Brazil where he held the position of Visiting Professor at the University of Sao Paulo (2015 to 2018).
    Ann Vossen
    Leiden University Medical Centre, Department of Medical Microbiology, Leiden, The Netherlands
    Ann Vossen, M.D., Ph.D., is Associate Professor of Clinical Virology at the Department of Medical Microbiology, Leiden University Medical Center. Her research focuses on congenital cytomegalovirus infection, including several large cohort studies on disease burden, virus-host interaction, and antiviral treatment. She is actively involved in the European Congenital CMV Initiative. Since 2018, she has been President of the Dutch Society of Medical Microbiology.
    Marion Koopmans
    Erasmus Medical Centre, Department of Viroscience, Rotterdam, The Netherlands
    Marion Koopmans, D.V.M., Ph.D., is head of the Department of Viroscience and director of the WHO collaborating center for arboviruses and viral hemorrhagic fevers, Erasmus Medical Centre, Rotterdam, The Netherlands. Her research focuses on the global population-level impact of rapidly spreading zoonotic and vector-borne virus infections, with an emphasis on improving preparedness and outbreak response through advanced laboratory studies. She is scientific coordinator of COMPARE, a large Horizon 2020-funded project (20 MEuro) exploring the potential uses of next-generation sequencing techniques for outbreak detection and tracking (www.compare-europe.eu), coprincipal investigator in the FP7-funded PREPARE project (www.prepare-europe.eu) aimed at building a pan-European operational network for rapid and large-scale European clinical research in response to infectious disease outbreaks with epidemic potential, and coprincipal investigator in ZIKALLIANCE. She has coauthored >500 papers that have been cited >20,000 times.

    Information & Contributors

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    Clinical Microbiology Reviews
    Volume 33Number 118 December 2019
    eLocator: e00130-18

    History

    Published online: 11 December 2019

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    KEYWORDS

    1. TORCH
    2. Zika virus
    3. congenital infections
    4. diagnostics
    5. fetal infection
    6. maternal infection
    7. molecular methods
    8. serology
    9. virology

    Contributors

    Authors

    Bettie Voordouw
    Erasmus Medical Centre, Department of Viroscience, Rotterdam, The Netherlands
    State Institute of Public Health and Environment, Department of Infectious Disease Diagnostics, Research, and Laboratory Surveillance, Bilthoven, The Netherlands
    Barry Rockx
    Erasmus Medical Centre, Department of Viroscience, Rotterdam, The Netherlands
    Thomas Jaenisch
    Heidelberg University Hospital, Department for Infectious Diseases, Heidelberg, Germany
    Pieter Fraaij
    Erasmus Medical Centre, Department of Viroscience, Rotterdam, The Netherlands
    Philippe Mayaud
    London School of Hygiene and Tropical Medicine, Department of Clinical Research, London, United Kingdom
    Ann Vossen
    Leiden University Medical Centre, Department of Medical Microbiology, Leiden, The Netherlands
    Marion Koopmans
    Erasmus Medical Centre, Department of Viroscience, Rotterdam, The Netherlands

    Notes

    Address correspondence to Bettie Voordouw, [email protected], or Marion Koopmans, [email protected].

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  • Clinical Microbiology ReviewsArticle
    The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

    The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

    SUMMARY

    The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

    ADDENDUM IN PROOF

    A new family of drug efflux transporters was recently reported (K. A. Hassan, Q. Liu, P. J. F. Henderson, and I. T. Paulsen, mBio 6:e01982-14, 2015, http://dx.doi.org/10.1128/mBio.01982-14). Also, a recent report describes the synthesis of derivatives of MBX2319, some of which are 30 times more potent than the original inhibitor, based on the potentiation of levofloxacin and piperacillin (S. T. Nguyen et al., Bioorg Med Chem, in press). Finally, Blair et al. discovered that AcrB protein of Salmonella Typhimurium from a patient treated with ciprofloxacin had a single amino acid substitution at the binding site, which made the pump more effective for fluoroquinolones and less effective for other antibiotics (J. M. A. Blair et al., Proc Natl Acad Sci U S A, in press, http://dx.doi.org/10.1073/pnas.1419939112).

    REFERENCES

    1.
    World Health Organization. 2014. Antimicrobial resistance: global report on surveillance. World Health Organization, Geneva, Switzerland.
    2.
    D'Costa VM, King CE, Kalan L, Morar M, Sung WW, Schwarz C, Froese D, Zazula G, Calmels F, Debruyne R, Golding GB, Poinar HN, Wright GD. 2011. Antibiotic resistance is ancient. Nature 477:457–461.
    3.
    Forsberg KJ, Patel S, Gibson MK, Lauber CL, Knight R, Fierer N, Dantas G. 2014. Bacterial phylogeny structures soil resistomes across habitats. Nature 509:612–616.
    4.
    Davies J, Davies D. 2010. Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev 74:417–433.
    5.
    Finley RL, Collignon P, Larsson DG, McEwen SA, Li X-Z, Gaze WH, Reid-Smith R, Timinouni M, Graham DW, Topp E. 2013. The scourge of antibiotic resistance: the important role of the environment. Clin Infect Dis 57:704–710.
    6.
    Centers for Disease Control and Prevention. 2013. Antibiotic resistance threats in the United States, 2013. Centers for Disease Control and Prevention, Atlanta, GA.
    7.
    Gottesman MM, Ling V. 2006. The molecular basis of multidrug resistance in cancer: the early years of P-glycoprotein research. FEBS Lett 580:998–1009.
    8.
    Levy SB. 1992. Active efflux mechanisms for antimicrobial resistance. Antimicrob Agents Chemother 36:695–703.
    9.
    Ma D, Cook DN, Alberti M, Pon NG, Nikaido H, Hearst JE. 1993. Molecular cloning and characterization of acrA and acrE genes of Escherichia coli. J Bacteriol 175:6299–6313.
    10.
    Poole K, Krebes K, McNally C, Neshat S. 1993. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol 175:7363–7372.
    11.
    Li X-Z, Livermore DM, Nikaido H. 1994. Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: resistance to tetracycline, chloramphenicol, and norfloxacin. Antimicrob Agents Chemother 38:1732–1741.
    12.
    Li X-Z, Ma D, Livermore DM, Nikaido H. 1994. Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: active efflux as a contributing factor to β-lactam resistance. Antimicrob Agents Chemother 38:1742–1752.
    13.
    Li X-Z, Nikaido H, Poole K. 1995. Role of MexA-MexB-OprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother 39:1948–1953.
    14.
    Nikaido H. 1994. Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264:382–388.
    15.
    Li X-Z, Nikaido H. 2004. Efflux-mediated drug resistance in bacteria. Drugs 64:159–204.
    16.
    Li X-Z, Nikaido H. 2009. Efflux-mediated drug resistance in bacteria: an update. Drugs 69:1555–1623.
    17.
    Saier MH, Jr, Tran CV, Barabote RD. 2006. TCDB: the Transporter Classification Database for membrane transport protein analyses and information. Nucleic Acids Res 34:D181–D186.
    18.
    Saier MH, Jr, Yen MR, Noto K, Tamang DG, Elkan C. 2009. The Transporter Classification Database: recent advances. Nucleic Acids Res 37:D274–D278.
    19.
    Saier MH, Jr, Reddy VS, Tamang DG, Vastermark A. 2014. The Transporter Classification Database. Nucleic Acids Res 42:D251–D258.
    20.
    Ren Q, Kang KH, Paulsen IT. 2004. TransportDB: a relational database of cellular membrane transport systems. Nucleic Acids Res 32:D284–D288.
    21.
    Nikaido H. 1989. Outer membrane barrier as a mechanism of antimicrobial resistance. Antimicrob Agents Chemother 33:1831–1836.
    22.
    Nikaido H. 2003. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 67:593–656.
    23.
    Aires JR, Nikaido H. 2005. Aminoglycosides are captured from both periplasm and cytoplasm by the AcrD multidrug efflux transporter of Escherichia coli. J Bacteriol 187:1923–1929.
    24.
    Nikaido H. 1996. Multidrug efflux pumps of Gram-negative bacteria. J Bacteriol 178:5853–5859.
    25.
    Lee A, Mao W, Warren MS, Mistry A, Hoshino K, Okumura R, Ishida H, Lomovskaya O. 2000. Interplay between efflux pumps may provide either additive or multiplicative effects on drug resistance. J Bacteriol 182:3142–3150.
    26.
    Tal N, Schuldiner S. 2009. A coordinated network of transporters with overlapping specificities provides a robust survival strategy. Proc Natl Acad Sci U S A 106:9051–9056.
    27.
    Sulavik MC, Houseweart C, Cramer C, Jiwani N, Murgolo N, Greene J, DiDomenico B, Shaw KJ, Miller GH, Hare R, Shimer G. 2001. Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes. Antimicrob Agents Chemother 45:1126–1136.
    28.
    Liu A, Tran L, Becket E, Lee K, Chinn L, Park E, Tran K, Miller JH. 2010. Antibiotic sensitivity profiles determined with an Escherichia coli gene knockout collection: generating an antibiotic bar code. Antimicrob Agents Chemother 54:1393–1403.
    29.
    Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H. 2006. Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol Syst Biol 2:2006.0008.
    30.
    Nichols RJ, Sen S, Choo YJ, Beltrao P, Zietek M, Chaba R, Lee S, Kazmierczak KM, Lee KJ, Wong A, Shales M, Lovett S, Winkler ME, Krogan NJ, Typas A, Gross CA. 2011. Phenotypic landscape of a bacterial cell. Cell 144:143–156.
    31.
    Nishino K, Yamaguchi A. 2001. Analysis of a complete library of putative drug transporter genes in Escherichia coli. J Bacteriol 183:5803–5812.
    32.
    Poole K. 2005. Efflux-mediated antimicrobial resistance. J Antimicrob Chemother 56:20–51.
    33.
    Poole K. 2007. Efflux pumps as antimicrobial resistance mechanisms. Ann Med 39:162–176.
    34.
    Piddock LJ. 2006. Multidrug-resistance efflux pumps—not just for resistance. Nat Rev Microbiol 4:629–636.
    35.
    Piddock LJ. 2006. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin Microbiol Rev 19:382–402.
    36.
    Piddock LJ. 2014. Understanding the basis of antibiotic resistance: a platform for drug discovery. Microbiology 160:2366–2373.
    37.
    Paulsen IT, Brown MH, Skurray RA. 1996. Proton-dependent multidrug efflux systems. Microbiol Rev 60:575–608.
    38.
    Saier MH, Jr, Paulsen IT, Sliwinski MK, Pao SS, Skurray RA, Nikaido H. 1998. Evolutionary origins of multidrug and drug-specific efflux pumps in bacteria. FASEB J 12:265–274.
    39.
    Van Bambeke F, Glupczynski Y, Plésiat P, Pechère JC, Tulkens PM. 2003. Antibiotic efflux pumps in prokaryotic cells: occurrence, impact on resistance and strategies for the future of antimicrobial therapy. J Antimicrob Chemother 51:1055–1065.
    40.
    Higgins CF. 2007. Multiple molecular mechanisms for multidrug resistance transporters. Nature 446:749–757.
    41.
    Alekshun MN, Levy SB. 2007. Molecular mechanisms of antibacterial multidrug resistance. Cell 128:1037–1050.
    42.
    Nikaido H. 1998. The role of outer membrane and efflux pumps in the resistance of Gram-negative bacteria. Can we improve drug access? Drug Resist Updat 1:93–98.
    43.
    Nikaido H. 2001. Preventing drug access to targets: cell surface permeability barriers and active efflux in bacteria. Semin Cell Dev Biol 12:215–223.
    44.
    Nikaido H, Takatsuka Y. 2009. Mechanisms of RND multidrug efflux pumps. Biochim Biophys Acta 1794:769–781.
    45.
    Nikaido H. 2011. Structure and mechanism of RND-type multidrug efflux pumps. Adv Enzymol Relat Areas Mol Biol 77:1–60.
    46.
    Murakami S. 2008. Multidrug efflux transporter, AcrB—the pumping mechanism. Curr Opin Struct Biol 18:459–465.
    47.
    Ruggerone P, Murakami S, Pos KM, Vargiu AV. 2013. RND efflux pumps: structural information translated into function and inhibition mechanisms. Curr Top Med Chem 13:3079–3100.
    48.
    Blair JM, Piddock LJ. 2009. Structure, function and inhibition of RND efflux pumps in Gram-negative bacteria: an update. Curr Opin Microbiol 12:512–519.
    49.
    Pos KM. 2009. Drug transport mechanism of the AcrB efflux pump. Biochim Biophys Acta 1794:782–793.
    50.
    Ruggerone P, Vargiu AV, Collu F, Fischer N, Kandt C. 2013. Molecular dynamics computer simulations of multidrug RND efflux pumps. Comput Struct Biotechnol J 5:e201302008.
    51.
    Ramos JL, Duque E, Gallegos MT, Godoy P, Ramos-Gonzalez MI, Rojas A, Teran W, Segura A. 2002. Mechanisms of solvent tolerance in Gram-negative bacteria. Annu Rev Microbiol 56:743–768.
    52.
    Poole K. 2008. Bacterial multidrug efflux pumps serve other functions. Microbe Mag 3:179–185.
    53.
    Poole K. 2012. Stress responses as determinants of antimicrobial resistance in Gram-negative bacteria. Trends Microbiol 20:227–234.
    54.
    Poole K. 2014. Stress responses as determinants of antimicrobial resistance in Pseudomonas aeruginosa: multidrug efflux and more. Can J Microbiol 60:783–791.
    55.
    Lennen RM, Politz MG, Kruziki MA, Pfleger BF. 2013. Identification of transport proteins involved in free fatty acid efflux in Escherichia coli. J Bacteriol 195:135–144.
    56.
    Tsukagoshi N, Aono R. 2000. Entry into and release of solvents by Escherichia coli in an organic-aqueous two-liquid-phase system and substrate specificity of the AcrAB-TolC solvent-extruding pump. J Bacteriol 182:4803–4810.
    57.
    Zgurskaya HI, Nikaido H. 1999. Bypassing the periplasm: reconstitution of the AcrAB multidrug efflux pump of Escherichia coli. Proc Natl Acad Sci U S A 96:7190–7195.
    58.
    Nikaido H, Basina M, Nguyen V, Rosenberg EY. 1998. Multidrug efflux pump AcrAB of Salmonella typhimurium excretes only those β-lactam antibiotics containing lipophilic side chains. J Bacteriol 180:4686–4692.
    59.
    Neyfakh AA. 2002. Mystery of multidrug transporters: the answer can be simple. Mol Microbiol 44:1123–1130.
    60.
    Lomovskaya O, Warren MS, Lee A, Galazzo J, Fronko R, Lee M, Blais J, Cho D, Chamberland S, Renau T, Leger R, Hecker S, Watkins W, Hoshino K, Ishida H, Lee VJ. 2001. Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa: novel agents for combination therapy. Antimicrob Agents Chemother 45:105–116.
    61.
    Murakami S, Tamura N, Saito A, Hirata T, Yamaguchi A. 2004. Extramembrane central pore of multidrug exporter AcrB in Escherichia coli plays an important role in drug transport. J Biol Chem 279:3743–3748.
    62.
    Bohnert JA, Karamian B, Nikaido H. 2010. Optimized Nile red efflux assay of AcrAB-TolC multidrug efflux system shows competition between substrates. Antimicrob Agents Chemother 54:3770–3775.
    63.
    Nagano K, Nikaido H. 2009. Kinetic behavior of the major multidrug efflux pump AcrB of Escherichia coli. Proc Natl Acad Sci U S A 106:5854–5858.
    64.
    Kojima S, Nikaido H. 2013. Permeation rates of penicillins indicate that Escherichia coli porins function principally as nonspecific channels. Proc Natl Acad Sci U S A 110:E2629–E2634.
    65.
    Lim SP, Nikaido H. 2010. Kinetic parameters of efflux of penicillins by the multidrug efflux transporter AcrAB-TolC of Escherichia coli. Antimicrob Agents Chemother 54:1800–1806.
    66.
    Murakami S, Nakashima R, Yamashita E, Yamaguchi A. 2002. Crystal structure of bacterial multidrug efflux transporter AcrB. Nature 419:587–593.
    67.
    Yu EW, Aires JR, McDermott G, Nikaido H. 2005. A periplasmic drug-binding site of the AcrB multidrug efflux pump: a crystallographic and site-directed mutagenesis study. J Bacteriol 187:6804–6815.
    68.
    Tornroth-Horsefield S, Gourdon P, Horsefield R, Brive L, Yamamoto N, Mori H, Snijder A, Neutze R. 2007. Crystal structure of AcrB in complex with a single transmembrane subunit reveals another twist. Structure 15:1663–1673.
    69.
    Yu EW, McDermott G, Zgurskaya HI, Nikaido H, Koshland DE, Jr. 2003. Structural basis of multiple drug-binding capacity of the AcrB multidrug efflux pump. Science 300:976–980.
    70.
    Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A. 2006. Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443:173–179.
    71.
    Seeger MA, Schiefner A, Eicher T, Verrey F, Diederichs K, Pos KM. 2006. Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science 313:1295–1298.
    72.
    Sennhauser G, Amstutz P, Briand C, Storchenegger O, Grutter MG. 2007. Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors. PLoS Biol 5:e7.
    73.
    Seeger MA, von Ballmoos C, Eicher T, Brandstatter L, Verrey F, Diederichs K, Pos KM. 2008. Engineered disulfide bonds support the functional rotation mechanism of multidrug efflux pump AcrB. Nat Struct Mol Biol 15:199–205.
    74.
    Sennhauser G, Bukowska MA, Briand C, Grutter MG. 2009. Crystal structure of the multidrug exporter MexB from Pseudomonas aeruginosa. J Mol Biol 389:134–145.
    75.
    Nakashima R, Sakurai K, Yamasaki S, Hayashi K, Nagata C, Hoshino K, Onodera Y, Nishino K, Yamaguchi A. 2013. Structural basis for the inhibition of bacterial multidrug exporters. Nature 500:102–106.
    76.
    Takatsuka Y, Nikaido H. 2009. Covalently linked trimer of the AcrB multidrug efflux pump provides support for the functional rotating mechanism. J Bacteriol 191:1729–1737.
    77.
    Eicher T, Cha HJ, Seeger MA, Brandstatter L, El-Delik J, Bohnert JA, Kern WV, Verrey F, Grutter MG, Diederichs K, Pos KM. 2012. Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop. Proc Natl Acad Sci U S A 109:5687–5692.
    78.
    Nakashima R, Sakurai K, Yamasaki S, Nishino K, Yamaguchi A. 2011. Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket. Nature 480:565–569.
    79.
    Husain F, Nikaido H. 2010. Substrate path in the AcrB multidrug efflux pump of Escherichia coli. Mol Microbiol 78:320–330.
    80.
    Drew D, Klepsch MM, Newstead S, Flaig R, De Gier JW, Iwata S, Beis K. 2008. The structure of the efflux pump AcrB in complex with bile acid. Mol Membr Biol 25:677–682.
    81.
    Kobayashi N, Tamura N, van Veen HW, Yamaguchi A, Murakami S. 2014. β-Lactam selectivity of multidrug transporters AcrB and AcrD resides in the proximal binding pocket. J Biol Chem 289:10680–10690.
    82.
    Lau CH, Hughes D, Poole K. 2014. MexY-promoted aminoglycoside resistance in Pseudomonas aeruginosa: involvement of a putative proximal binding pocket in aminoglycoside recognition. mBio 5(2):e01068-14.
    83.
    Yu EW, Aires JR, Nikaido H. 2003. AcrB multidrug efflux pump of Escherichia coli: composite substrate-binding cavity of exceptional flexibility generates its extremely wide substrate specificity. J Bacteriol 185:5657–5664.
    84.
    Husain F, Bikhchandani M, Nikaido H. 2011. Vestibules are part of the substrate path in the multidrug efflux transporter AcrB of Escherichia coli. J Bacteriol 193:5847–5849.
    85.
    Hung LW, Kim HB, Murakami S, Gupta G, Kim CY, Terwilliger TC. 2013. Crystal structure of AcrB complexed with linezolid at 3.5 A resolution. J Struct Funct Genomics 14:71–75.
    86.
    Dastidar V, Mao W, Lomovskaya O, Zgurskaya HI. 2007. Drug-induced conformational changes in multidrug efflux transporter AcrB from Haemophilus influenzae. J Bacteriol 189:5550–5558.
    87.
    Bohnert JA, Schuster S, Seeger MA, Fahnrich E, Pos KM, Kern WV. 2008. Site-directed mutagenesis reveals putative substrate binding residues in the Escherichia coli RND efflux pump AcrB. J Bacteriol 190:8225–8229.
    88.
    Vargiu AV, Collu F, Schulz R, Pos KM, Zacharias M, Kleinekathofer U, Ruggerone P. 2011. Effect of the F610A mutation on substrate extrusion in the AcrB transporter: explanation and rationale by molecular dynamics simulations. J Am Chem Soc 133:10704–10707.
    89.
    Wehmeier C, Schuster S, Fahnrich E, Kern WV, Bohnert JA. 2009. Site-directed mutagenesis reveals amino acid residues in the Escherichia coli RND efflux pump AcrB that confer macrolide resistance. Antimicrob Agents Chemother 53:329–330.
    90.
    Eicher T, Seeger MA, Anselmi C, Zhou W, Brandstatter L, Verrey F, Diederichs K, Faraldo-Gomez JD, Pos KM. 2014. Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB. eLife 3:e03145.
    91.
    Takatsuka Y, Chen C, Nikaido H. 2010. Mechanism of recognition of compounds of diverse structures by the multidrug efflux pump AcrB of Escherichia coli. Proc Natl Acad Sci U S A 107:6559–6565.
    92.
    Elkins CA, Mullis LB. 2007. Substrate competition studies using whole-cell accumulation assays with the major tripartite multidrug efflux pumps of Escherichia coli. Antimicrob Agents Chemother 51:923–929.
    93.
    Vargiu AV, Nikaido H. 2012. Multidrug binding properties of the AcrB efflux pump characterized by molecular dynamics simulations. Proc Natl Acad Sci U S A 109:20637–20642.
    94.
    Kinana AD, Vargiu AV, Nikaido H. 2013. Some ligands enhance the efflux of other ligands by the Escherichia coli multidrug pump AcrB. Biochemistry 52:8342–8351.
    95.
    Opperman TJ, Kwasny SM, Kim HS, Nguyen ST, Houseweart C, D'Souza S, Walker GC, Peet NP, Nikaido H, Bowlin TL. 2014. Characterization of a novel pyranopyridine inhibitor of the AcrAB efflux pump of Escherichia coli. Antimicrob Agents Chemother 58:722–733.
    96.
    Vargiu AV, Ruggerone P, Opperman TJ, Nguyen ST, Nikaido H. 2014. Inhibition of E. coli AcrB multidrug efflux pump by MBX2319: molecular mechanism and comparison with other inhibitors. Antimicrob Agents Chemother 58:6224–6234.
    97.
    Schumacher MA, Brennan RG. 2003. Deciphering the molecular basis of multidrug recognition: crystal structures of the Staphylococcus aureus multidrug binding transcription regulator QacR. Res Microbiol 154:69–77.
    98.
    Schumacher MA, Miller MC, Brennan RG. 2004. Structural mechanism of the simultaneous binding of two drugs to a multidrug-binding protein. EMBO J 23:2923–2930.
    99.
    Schulz R, Vargiu AV, Collu F, Kleinekathofer U, Ruggerone P. 2010. Functional rotation of the transporter AcrB: insights into drug extrusion from simulations. PLoS Comput Biol 6:e1000806.
    100.
    Feng Z, Hou T, Li Y. 2012. Unidirectional peristaltic movement in multisite drug binding pockets of AcrB from molecular dynamics simulations. Mol Biosyst 8:2699–2709.
    101.
    Fischer N, Kandt C. 2011. Three ways in, one way out: water dynamics in the trans-membrane domains of the inner membrane translocase AcrB. Proteins 79:2871–2885.
    102.
    Schulz R, Vargiu AV, Ruggerone P, Kleinekathofer U. 2011. Role of water during the extrusion of substrates by the efflux transporter AcrB. J Phys Chem B 115:8278–8287.
    103.
    Yao XQ, Kenzaki H, Murakami S, Takada S. 2010. Drug export and allosteric coupling in a multidrug transporter revealed by molecular simulations. Nat Commun 1:117.
    104.
    Yao XQ, Kimura N, Murakami S, Takada S. 2013. Drug uptake pathways of multidrug transporter AcrB studied by molecular simulations and site-directed mutagenesis experiments. J Am Chem Soc 135:7474–7485.
    105.
    Murakami S, Yamaguchi A. 2003. Multidrug-exporting secondary transporters. Curr Opin Struct Biol 13:443–452.
    106.
    Takatsuka Y, Nikaido H. 2006. Threonine-978 in the transmembrane segment of the multidrug efflux pump AcrB of Escherichia coli is crucial for drug transport as a probable component of the proton relay network. J Bacteriol 188:7284–7289.
    107.
    Seeger MA, von Ballmoos C, Verrey F, Pos KM. 2009. Crucial role of Asp408 in the proton translocation pathway of multidrug transporter AcrB: evidence from site-directed mutagenesis and carbodiimide labeling. Biochemistry 48:5801–5812.
    108.
    Yamane T, Murakami S, Ikeguchi M. 2013. Functional rotation induced by alternating protonation states in the multidrug transporter AcrB: all-atom molecular dynamics simulations. Biochemistry 52:7648–7658.
    109.
    Lu W, Zhong M, Wei Y. 2011. Folding of AcrB subunit precedes trimerization. J Mol Biol 411:264–274.
    110.
    Fang J, Yu L, Wu M, Wei Y. 2013. Dissecting the function of a protruding loop in AcrB trimerization. J Biomol Struct Dyn 31:385–392.
    111.
    Pogliano KJ, Beckwith J. 1994. Genetic and molecular characterization of the Escherichia coli secD operon and its products. J Bacteriol 176:804–814.
    112.
    Hobbs EC, Yin X, Paul BJ, Astarita JL, Storz G. 2012. Conserved small protein associates with the multidrug efflux pump AcrB and differentially affects antibiotic resistance. Proc Natl Acad Sci U S A 109:16696–16701.
    113.
    Koronakis V, Sharff A, Koronakis E, Luisi B, Hughes C. 2000. Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export. Nature 405:914–919.
    114.
    Akama H, Matsuura T, Kashiwagi S, Yoneyama H, Narita S, Tsukihara T, Nakagawa A, Nakae T. 2004. Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa. J Biol Chem 279:25939–25942.
    115.
    Mikolosko J, Bobyk K, Zgurskaya HI, Ghosh P. 2006. Conformational flexibility in the multidrug efflux system protein AcrA. Structure 14:577–587.
    116.
    Symmons MF, Bokma E, Koronakis E, Hughes C, Koronakis V. 2009. The assembled structure of a complete tripartite bacterial multidrug efflux pump. Proc Natl Acad Sci U S A 106:7173–7178.
    117.
    Tamura N, Murakami S, Oyama Y, Ishiguro M, Yamaguchi A. 2005. Direct interaction of multidrug efflux transporter AcrB and outer membrane channel TolC detected via site-directed disulfide cross-linking. Biochemistry 44:11115–11121.
    118.
    Tikhonova EB, Zgurskaya HI. 2004. AcrA, AcrB, and TolC of Escherichia coli form a stable intermembrane multidrug efflux complex. J Biol Chem 279:32116–32124.
    119.
    Tikhonova EB, Dastidar V, Rybenkov VV, Zgurskaya HI. 2009. Kinetic control of TolC recruitment by multidrug efflux complexes. Proc Natl Acad Sci U S A 106:16416–16421.
    120.
    Tikhonova EB, Yamada Y, Zgurskaya HI. 2011. Sequential mechanism of assembly of multidrug efflux pump AcrAB-TolC. Chem Biol 18:454–463.
    121.
    Yum S, Xu Y, Piao S, Sim SH, Kim HM, Jo WS, Kim KJ, Kweon HS, Jeong MH, Jeon H, Lee K, Ha NC. 2009. Crystal structure of the periplasmic component of a tripartite macrolide-specific efflux pump. J Mol Biol 387:1286–1297.
    122.
    Su CC, Long F, Zimmermann MT, Rajashankar KR, Jernigan RL, Yu EW. 2011. Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli. Nature 470:558–562.
    123.
    Du D, Wang Z, James NR, Voss JE, Klimont E, Ohene-Agyei T, Venter H, Chiu W, Luisi BF. 2014. Structure of the AcrAB-TolC multidrug efflux pump. Nature 509:512–515.
    124.
    Kobayashi K, Tsukagoshi N, Aono R. 2001. Suppression of hypersensitivity of Escherichia coli acrB mutant to organic solvents by integrational activation of the acrEF operon with the IS1 or IS2 element. J Bacteriol 183:2646–2653.
    125.
    Olliver A, Valle M, Chaslus-Dancla E, Cloeckaert A. 2005. Overexpression of the multidrug efflux operon acrEF by insertional activation with IS1 or IS10 elements in Salmonella enterica serovar Typhimurium DT204 acrB mutants selected with fluoroquinolones. Antimicrob Agents Chemother 49:289–301.
    126.
    Zhang Y, Xiao M, Horiyama T, Zhang Y, Li X, Nishino K, Yan A. 2011. The multidrug efflux pump MdtEF protects against nitrosative damage during the anaerobic respiration in Escherichia coli. J Biol Chem 286:26576–26584.
    127.
    Kim HS, Nagore D, Nikaido H. 2010. Multidrug efflux pump MdtBC of Escherichia coli is active only as a B2C heterotrimer. J Bacteriol 192:1377–1386.
    128.
    Baranova N, Nikaido H. 2002. The baeSR two-component regulatory system activates transcription of the yegMNOB (mdtABCD) transporter gene cluster in Escherichia coli and increases its resistance to novobiocin and deoxycholate. J Bacteriol 184:4168–4176.
    129.
    Kim HS, Nikaido H. 2012. Different functions of MdtB and MdtC subunits in the heterotrimeric efflux transporter MdtB2C complex of Escherichia coli. Biochemistry 51:4188–4197.
    130.
    Reddy VS, Shlykov MA, Castillo R, Sun EI, Saier MH, Jr. 2012. The major facilitator superfamily (MFS) revisited. FEBS J 279:2022–2035.
    131.
    Ohene-Agyei T, Lea JD, Venter H. 2012. Mutations in MexB that affect the efflux of antibiotics with cytoplasmic targets. FEMS Microbiol Lett 333:20–27.
    132.
    Sapunaric FM, Aldema-Ramos M, McMurry LM. 2005. Tetracycline resistance: efflux, mutation, and other mechanisms, p 3–18. In White DG, Alekshun MN, McDermot PF (ed), Frontiers in antimicrobial resistance. A tribute to Stuart B. Levy. ASM Press, Washington, DC.
    133.
    McMurry L, Petrucci RE, Jr, Levy SB. 1980. Active efflux of tetracycline encoded by four genetically different tetracycline resistance determinants in Escherichia coli. Proc Natl Acad Sci U S A 77:3974–3977.
    134.
    Yamaguchi A, Udagawa T, Sawai T. 1990. Transport of divalent cations with tetracycline as mediated by the transposon Tn10-encoded tetracycline resistance protein. J Biol Chem 265:4809–4813.
    135.
    Tamura N, Konishi S, Yamaguchi A. 2003. Mechanisms of drug/H+ antiport: complete cysteine-scanning mutagenesis and the protein engineering approach. Curr Opin Chem Biol 7:570–579.
    136.
    Krulwich TA, Jin J, Guffanti AA, Bechhofer H. 2001. Functions of tetracycline efflux proteins that do not involve tetracycline. J Mol Microbiol Biotechnol 3:237–246.
    137.
    Petersen PJ, Jacobus NV, Weiss WJ, Sum PE, Testa RT. 1999. In vitro and in vivo antibacterial activities of a novel glycylcycline, the 9-t-butylglycylamido derivative of minocycline (GAR-936). Antimicrob Agents Chemother 43:738–744.
    138.
    Hirata T, Saito A, Nishino K, Tamura N, Yamaguchi A. 2004. Effects of efflux transporter genes on susceptibility of Escherichia coli to tigecycline (GAR-936). Antimicrob Agents Chemother 48:2179–2184.
    139.
    Lomovskaya O, Lewis K. 1992. Emr, an Escherichia coli locus for multidrug resistance. Proc Natl Acad Sci U S A 89:8938–8942.
    140.
    May T, Ito A, Okabe S. 2009. Induction of multidrug resistance mechanism in Escherichia coli biofilms by interplay between tetracycline and ampicillin resistance genes. Antimicrob Agents Chemother 53:4628–4639.
    141.
    Yin Y, He X, Szewczyk P, Nguyen T, Chang G. 2006. Structure of the multidrug transporter EmrD from Escherichia coli. Science 312:741–744.
    142.
    Steed PR, Zou P, Trone KE, McHaourab HS. 2013. Structure and pH-induced structural rearrangements of the putative multidrug efflux pump EmrD in liposomes probed by site-directed spin labeling. Biochemistry 52:7964–7974.
    143.
    Tanabe M, Szakonyi G, Brown KA, Henderson PJ, Nield J, Byrne B. 2009. The multidrug resistance efflux complex, EmrAB from Escherichia coli forms a dimer in vitro. Biochem Biophys Res Commun 380:338–342.
    144.
    Borges-Walmsley MI, Beauchamp J, Kelly SM, Jumel K, Candlish D, Harding SE, Price NC, Walmsley AR. 2003. Identification of oligomerization and drug-binding domains of the membrane fusion protein EmrA. J Biol Chem 278:12903–12912.
    145.
    Edgar R, Bibi E. 1997. MdfA, an Escherichia coli multidrug resistance protein with an extraordinarily broad spectrum of drug recognition. J Bacteriol 179:2274–2280.
    146.
    Fluman N, Bibi E. 2009. Bacterial multidrug transport through the lens of the major facilitator superfamily. Biochim Biophys Acta 1794:738–747.
    147.
    Cannon RD, Lamping E, Holmes AR, Niimi K, Baret PV, Keniya MV, Tanabe K, Niimi M, Goffeau A, Monk BC. 2009. Efflux-mediated antifungal drug resistance. Clin Microbiol Rev 22:291–321.
    148.
    Woebking B, Reuter G, Shilling RA, Velamakanni S, Shahi S, Venter H, Balakrishnan L, van Veen HW. 2005. Drug-lipid A interactions on the Escherichia coli ABC transporter MsbA. J Bacteriol 187:6363–6369.
    149.
    Kobayashi N, Nishino K, Yamaguchi A. 2001. Novel macrolide-specific ABC-type efflux transporter in Escherichia coli. J Bacteriol 183:5639–5644.
    150.
    Tikhonova EB, Devroy VK, Lau SY, Zgurskaya HI. 2007. Reconstitution of the Escherichia coli macrolide transporter: the periplasmic membrane fusion protein MacA stimulates the ATPase activity of MacB. Mol Microbiol 63:895–910.
    151.
    Lin HT, Bavro VN, Barrera NP, Frankish HM, Velamakanni S, van Veen HW, Robinson CV, Borges-Walmsley MI, Walmsley AR. 2009. MacB ABC transporter is a dimer whose ATPase activity and macrolide-binding capacity are regulated by the membrane fusion protein MacA. J Biol Chem 284:1145–1154.
    152.
    Lu S, Zgurskaya HI. 2012. Role of ATP binding and hydrolysis in assembly of MacAB-TolC macrolide transporter. Mol Microbiol 86:1132–1143.
    153.
    Guisbert E, Yura T, Rhodius VA, Gross CA. 2008. Convergence of molecular, modeling, and systems approaches for an understanding of the Escherichia coli heat shock response. Microbiol Mol Biol Rev 72:545–554.
    154.
    Lu S, Zgurskaya HI. 2013. MacA, a periplasmic membrane fusion protein of the macrolide transporter MacAB-TolC, binds lipopolysaccharide core specifically and with high affinity. J Bacteriol 195:4865–4872.
    155.
    Yerushalmi H, Lebendiker M, Schuldiner S. 1995. EmrE, an Escherichia coli 12-kDa multidrug transporter, exchanges toxic cations and H+ and is soluble in organic solvents. J Biol Chem 270:6856–6863.
    156.
    Nasie I, Steiner-Mordoch S, Schuldiner S. 2012. New substrates on the block: clinically relevant resistances for EmrE and homologues. J Bacteriol 194:6766–6770.
    157.
    Chen YJ, Pornillos O, Lieu S, Ma C, Chen AP, Chang G. 2007. X-ray structure of EmrE supports dual topology model. Proc Natl Acad Sci U S A 104:18999–19004.
    158.
    Schuldiner S. 2012. Undecided membrane proteins insert in random topologies. Up, down and sideways: it does not really matter. Trends Biochem Sci 37:215–219.
    159.
    Bay DC, Turner RJ. 2012. Small multidrug resistance protein EmrE reduces host pH and osmotic tolerance to metabolic quaternary cation osmoprotectants. J Bacteriol 194:5941–5948.
    160.
    Beketskaia MS, Bay DC, Turner RJ. 2014. Outer membrane protein OmpW participates with small multidrug resistance protein member EmrE in quaternary cationic compound efflux. J Bacteriol 196:1908–1914.
    161.
    Hong H, Patel DR, Tamm LK, van den Berg B. 2006. The outer membrane protein OmpW forms an eight-stranded β-barrel with a hydrophobic channel. J Biol Chem 281:7568–7577.
    162.
    Srinivasan VB, Rajamohan G, Gebreyes WA. 2009. Role of AbeS, a novel efflux pump of the SMR family of transporters, in resistance to antimicrobial agents in Acinetobacter baumannii. Antimicrob Agents Chemother 53:5312–5316.
    163.
    Srinivasan VB, Rajamohan G. 2013. KpnEF, a new member of the Klebsiella pneumoniae cell envelope stress response regulon, is an SMR-type efflux pump involved in broad-spectrum antimicrobial resistance. Antimicrob Agents Chemother 57:4449–4462.
    164.
    Li X-Z, Poole K, Nikaido H. 2003. Contributions of MexAB-OprM and an EmrE homolog to intrinsic resistance of Pseudomonas aeruginosa to aminoglycosides and dyes. Antimicrob Agents Chemother 47:27–33.
    165.
    Kuroda T, Tsuchiya T. 2009. Multidrug efflux transporters in the MATE family. Biochim Biophys Acta 1794:763–768.
    166.
    He X, Szewczyk P, Karyakin A, Evin M, Hong WX, Zhang Q, Chang G. 2010. Structure of a cation-bound multidrug and toxic compound extrusion transporter. Nature 467:991–994.
    167.
    Lu M, Symersky J, Radchenko M, Koide A, Guo Y, Nie R, Koide S. 2013. Structures of a Na+-coupled, substrate-bound MATE multidrug transporter. Proc Natl Acad Sci U S A 110:2099–2104.
    168.
    Tanaka Y, Hipolito CJ, Maturana AD, Ito K, Kuroda T, Higuchi T, Katoh T, Kato HE, Hattori M, Kumazaki K, Tsukazaki T, Ishitani R, Suga H, Nureki O. 2013. Structural basis for the drug extrusion mechanism by a MATE multidrug transporter. Nature 496:247–251.
    169.
    Song J, Ji C, Zhang JZ. 2014. Insights on Na+ binding and conformational dynamics in multidrug and toxic compound extrusion transporter NorM. Proteins 82:240–249.
    170.
    He GX, Thorpe C, Walsh D, Crow R, Chen H, Kumar S, Varela MF. 2011. EmmdR, a new member of the MATE family of multidrug transporters, extrudes quinolones from Enterobacter cloacae. Arch Microbiol 193:759–765.
    171.
    Cowan SW, Schirmer T, Rummel G, Steiert M, Ghosh R, Pauptit RA, Jansonius JN, Rosenbusch JP. 1992. Crystal structures explain functional properties of two E. coli porins. Nature 358:727–733.
    172.
    Kamio Y, Nikaido H. 1976. Outer membrane of Salmonella typhimurium: accessibility of phospholipid head groups to phospholipase c and cyanogen bromide activated dextran in the external medium. Biochemistry 15:2561–2570.
    173.
    Schulz GE. 1993. Bacterial porins: structure and function. Curr Opin Cell Biol 5:701–707.
    174.
    Nikaido H, Rosenberg EY. 1983. Porin channels in Escherichia coli: studies with liposomes reconstituted from purified proteins. J Bacteriol 153:241–252.
    175.
    Stock JB, Rauch B, Roseman S. 1977. Periplasmic space in Salmonella typhimurium and Escherichia coli. J Biol Chem 252:7850–7861.
    176.
    Vaara M. 1992. Agents that increase the permeability of the outer membrane. Microbiol Rev 56:395–411.
    177.
    Vaara M. 1993. Antibiotic-supersusceptible mutants of Escherichia coli and Salmonella typhimurium. Antimicrob Agents Chemother 37:2255–2260.
    178.
    Koebnik R. 1995. Proposal for a peptidoglycan-associating alpha-helical motif in the C-terminal regions of some bacterial cell-surface proteins. Mol Microbiol 16:1269–1270.
    179.
    Sugawara E, Nestorovich EM, Bezrukov SM, Nikaido H. 2006. Pseudomonas aeruginosa porin OprF exists in two different conformations. J Biol Chem 281:16220–16229.
    180.
    Sugawara E, Nagano K, Nikaido H. 2010. Factors affecting the folding of Pseudomonas aeruginosa OprF porin into the one-domain open conformer. mBio 1(4):e00228-10.
    181.
    Yoshimura F, Nikaido H. 1982. Permeability of Pseudomonas aeruginosa outer membrane to hydrophilic solutes. J Bacteriol 152:636–642.
    182.
    Angus BL, Carey AM, Caron DA, Kropinski AM, Hancock RE. 1982. Outer membrane permeability in Pseudomonas aeruginosa: comparison of a wild-type with an antibiotic-supersusceptible mutant. Antimicrob Agents Chemother 21:299–309.
    183.
    Sugawara E, Nikaido H. 2012. OmpA is the principal nonspecific slow porin of Acinetobacter baumannii. J Bacteriol 194:4089–4096.
    184.
    Coyne S, Courvalin P, Perichon B. 2011. Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother 55:947–953.
    185.
    Plésiat P, Nikaido H. 1992. Outer membranes of Gram-negative bacteria are permeable to steroid probes. Mol Microbiol 6:1323–1333.
    186.
    Elkins CA, Mullis LB. 2006. Mammalian steroid hormones are substrates for the major RND- and MFS-type tripartite multidrug efflux pumps of Escherichia coli. J Bacteriol 188:1191–1195.
    187.
    Li X-Z, Zhang L, Poole K. 2000. Interplay between the MexA-MexB-OprM multidrug efflux system and the outer membrane barrier in the multiple antibiotic resistance of Pseudomonas aeruginosa. J Antimicrob Chemother 45:433–436.
    188.
    Mazzariol A, Cornaglia G, Nikaido H. 2000. Contributions of the AmpC β-lactamase and the AcrAB multidrug efflux system in intrinsic resistance of Escherichia coli K-12 to β-lactams. Antimicrob Agents Chemother 44:1387–1390.
    189.
    Nikaido H, Liu W, Rosenberg EY. 1990. Outer membrane permeability and β-lactamase stability of dipolar ionic cephalosporins containing methoxyimino substituents. Antimicrob Agents Chemother 34:337–342.
    190.
    Trias J, Nikaido H. 1990. Protein D2 channel of the Pseudomonas aeruginosa outer membrane has a binding site for basic amino acids and peptides. J Biol Chem 265:15680–15684.
    191.
    Plésiat P, Aires JR, Godard C, Kohler T. 1997. Use of steroids to monitor alterations in the outer membrane of Pseudomonas aeruginosa. J Bacteriol 179:7004–7010.
    192.
    Croxen MA, Law RJ, Scholz R, Keeney KM, Wlodarska M, Finlay BB. 2013. Recent advances in understanding enteric pathogenic Escherichia coli. Clin Microbiol Rev 26:822–880.
    193.
    Bush K. 2013. Proliferation and significance of clinically relevant β-lactamases. Ann N Y Acad Sci 1277:84–90.
    194.
    Kronvall G. 2010. Antimicrobial resistance 1979-2009 at Karolinska hospital, Sweden: normalized resistance interpretation during a 30-year follow-up on Staphylococcus aureus and Escherichia coli resistance development. APMIS 118:621–639.
    195.
    European Center for Disease Prevention and Control. 2013. Antimicrobial resistance surveillance in Europe 2012. European Center for Disease Prevention and Control, Stockholm, Sweden.
    196.
    Everett MJ, Jin YF, Ricci V, Piddock LJ. 1996. Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals. Antimicrob Agents Chemother 40:2380–2386.
    197.
    Oethinger M, Kern WV, Goldman JD, Levy SB. 1998. Association of organic solvent tolerance and fluoroquinolone resistance in clinical isolates of Escherichia coli. J Antimicrob Chemother 41:111–114.
    198.
    Oethinger M, Podglajen I, Kern WV, Levy SB. 1998. Overexpression of the marA or soxS regulatory gene in clinical topoisomerase mutants of Escherichia coli. Antimicrob Agents Chemother 42:2089–2094.
    199.
    Yasufuku T, Shigemura K, Shirakawa T, Matsumoto M, Nakano Y, Tanaka K, Arakawa S, Kinoshita S, Kawabata M, Fujisawa M. 2011. Correlation of overexpression of efflux pump genes with antibiotic resistance in Escherichia coli strains clinically isolated from urinary tract infection patients. J Clin Microbiol 49:189–194.
    200.
    Swick MC, Morgan-Linnell SK, Carlson KM, Zechiedrich L. 2011. Expression of multidrug efflux pump genes acrAB-tolC, mdfA, and norE in Escherichia coli clinical isolates as a function of fluoroquinolone and multidrug resistance. Antimicrob Agents Chemother 55:921–924.
    201.
    Alekshun MN, Levy SB. 1997. Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon. Antimicrob Agents Chemother 41:2067–2075.
    202.
    Buffet-Bataillon S, Le Jeune A, Le Gall-David S, Bonnaure-Mallet M, Jolivet-Gougeon A. 2012. Molecular mechanisms of higher MICs of antibiotics and quaternary ammonium compounds for Escherichia coli isolated from bacteraemia. J Antimicrob Chemother 67:2837–2842.
    203.
    Wang H, Dzink-Fox JL, Chen M, Levy SB. 2001. Genetic characterization of highly fluoroquinolone-resistant clinical Escherichia coli strains from China: role of acrR mutations. Antimicrob Agents Chemother 45:1515–1521.
    204.
    Lautenbach E, Metlay JP, Mao X, Han X, Fishman NO, Bilker WB, Tolomeo P, Wheeler M, Nachamkin I. 2010. The prevalence of fluoroquinolone resistance mechanisms in colonizing Escherichia coli isolates recovered from hospitalized patients. Clin Infect Dis 51:280–285.
    205.
    Karczmarczyk M, Martins M, Quinn T, Leonard N, Fanning S. 2011. Mechanisms of fluoroquinolone resistance in Escherichia coli isolates from food-producing animals. Appl Environ Microbiol 77:7113–7120.
    206.
    Yamane K, Wachino J, Suzuki S, Kimura K, Shibata N, Kato H, Shibayama K, Konda T, Arakawa Y. 2007. New plasmid-mediated fluoroquinolone efflux pump, QepA, found in an Escherichia coli clinical isolate. Antimicrob Agents Chemother 51:3354–3360.
    207.
    Nikaido H, Rosenberg EY, Foulds J. 1983. Porin channels in Escherichia coli: studies with β-lactams in intact cells. J Bacteriol 153:232–240.
    208.
    Yoshimura F, Nikaido H. 1985. Diffusion of β-lactam antibiotics through the porin channels of Escherichia coli K-12. Antimicrob Agents Chemother 27:84–92.
    209.
    Harder KJ, Nikaido H, Matsuhashi M. 1981. Mutants of Escherichia coli that are resistant to certain β-lactam compounds lack the OmpF porin. Antimicrob Agents Chemother 20:549–552.
    210.
    Galleni M, Amicosante G, Frère JM. 1988. A survey of the kinetic parameters of class C β-lactamases. Cephalosporins and other β-lactam compounds. Biochem J 255:123–129.
    211.
    Jaffe A, Chabbert YA, Semonin O. 1982. Role of porin proteins OmpF and OmpC in the permeation of β-lactams. Antimicrob Agents Chemother 22:942–948.
    212.
    Perilli M, Segatore B, Tavio M, Setacci D, Celenza G, De Santis F, Pellegrini C, Rossolini GM, Amicosante G. 2007. In vitro selection and characterization of mutants in TEM-1-producing Escherichia coli by ceftazidime and ceftibuten. J Chemother 19:123–126.
    213.
    Reguera JA, Baquero F, Pérez-Diaz JC, Martínez JL. 1991. Factors determining resistance to β-lactam combined with β-lactamase inhibitors in Escherichia coli. J Antimicrob Chemother 27:569–575.
    214.
    Martínez-Martínez L, Conejo MC, Pascual A, Hernández-Allés S, Ballesta S, Ramirez De Arellano-Ramos E, Benedi VJ, Perea EJ. 2000. Activities of imipenem and cephalosporins against clonally related strains of Escherichia coli hyperproducing chromosomal β-lactamase and showing altered porin profiles. Antimicrob Agents Chemother 44:2534–2536.
    215.
    Tenover FC, Raney PM, Williams PP, Rasheed JK, Biddle JW, Oliver A, Fridkin SK, Jevitt L, McGowan JE, Jr, Project ICARE. 2003. Evaluation of the NCCLS extended-spectrum β-lactamase confirmation methods for Escherichia coli with isolates collected during Project ICARE. J Clin Microbiol 41:3142–3146.
    216.
    Palasubramaniam S, Subramaniam G, Muniandy S, Parasakthi N. 2007. Extended-spectrum β-lactam resistance due to AmpC hyperproduction and CMY-2 coupled with the loss of OmpK35 in Malaysian strains of Escherichia coli and Klebsiella pneumoniae. Microb Drug Resist 13:186–190.
    217.
    Stapleton PD, Shannon KP, French GL. 1999. Carbapenem resistance in Escherichia coli associated with plasmid-determined CMY-4 β-lactamase production and loss of an outer membrane protein. Antimicrob Agents Chemother 43:1206–1210.
    218.
    Tangden T, Adler M, Cars O, Sandegren L, Lowdin E. 2013. Frequent emergence of porin-deficient subpopulations with reduced carbapenem susceptibility in ESBL-producing Escherichia coli during exposure to ertapenem in an in vitro pharmacokinetic model. J Antimicrob Chemother 68:1319–1326.
    219.
    Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. 2000. Contribution of the MexX-MexY-OprM efflux system to intrinsic resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 44:2242–2246.
    220.
    Kothary V, Scherl EJ, Bosworth B, Jiang ZD, Dupont HL, Harel J, Simpson KW, Dogan B. 2013. Rifaximin resistance in Escherichia coli associated with inflammatory bowel disease correlates with prior rifaximin use, mutations in rpoB, and activity of Phe-Arg-β-naphthylamide-inhibitable efflux pumps. Antimicrob Agents Chemother 57:811–817.
    221.
    Medeiros AA, O'Brien TF, Rosenberg EY, Nikaido H. 1987. Loss of OmpC porin in a strain of Salmonella typhimurium causes increased resistance to cephalosporins during therapy. J Infect Dis 156:751–757.
    222.
    Nishino K, Latifi T, Groisman EA. 2006. Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium. Mol Microbiol 59:126–141.
    223.
    Nishino K, Nikaido E, Yamaguchi A. 2007. Regulation of multidrug efflux systems involved in multidrug and metal resistance of Salmonella enterica serovar Typhimurium. J Bacteriol 189:9066–9075.
    224.
    Nishino K, Hayashi-Nishino M, Yamaguchi A. 2009. H-NS modulates multidrug resistance of Salmonella enterica serovar Typhimurium by repressing multidrug efflux genes acrEF. Antimicrob Agents Chemother 53:3541–3543.
    225.
    Piddock LJ, Griggs DJ, Hall MC, Jin YF. 1993. Ciprofloxacin resistance in clinical isolates of Salmonella typhimurium obtained from two patients. Antimicrob Agents Chemother 37:662–666.
    226.
    Chen S, Cui S, McDermott PF, Zhao S, White DG, Paulsen I, Meng J. 2007. Contribution of target gene mutations and efflux to decreased susceptibility of Salmonella enterica serovar Typhimurium to fluoroquinolones and other antimicrobials. Antimicrob Agents Chemother 51:535–542.
    227.
    Baucheron S, Imberechts H, Chaslus-Dancla E, Cloeckaert A. 2002. The AcrB multidrug transporter plays a major role in high-level fluoroquinolone resistance in Salmonella enterica serovar Typhimurium phage type DT204. Microb Drug Resist 8:281–289.
    228.
    Lunn AD, Fabrega A, Sánchez-Cespedes J, Vila J. 2010. Prevalence of mechanisms decreasing quinolone-susceptibility among Salmonella spp. clinical isolates. Int Microbiol 13:15–20.
    229.
    O'Regan E, Quinn T, Pagès JM, McCusker M, Piddock L, Fanning S. 2009. Multiple regulatory pathways associated with high-level ciprofloxacin and multidrug resistance in Salmonella enterica serovar Enteritidis: involvement of ramA and other global regulators. Antimicrob Agents Chemother 53:1080–1087.
    230.
    Smith AM, Govender N, Keddy KH, Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa. 2010. Quinolone-resistant Salmonella Typhi in South Africa, 2003-2007. Epidemiol Infect 138:86–90.
    231.
    Bergstrom S, Lindberg FP, Olsson O, Normark S. 1983. Comparison of the overlapping frd and ampC operons of Escherichia coli with the corresponding DNA sequences in other Gram-negative bacteria. J Bacteriol 155:1297–1305.
    232.
    Butaye P, Michael GB, Schwarz S, Barrett TJ, Brisabois A, White DG. 2006. The clonal spread of multidrug-resistant non-Typhi Salmonella serotypes. Microbes Infect 8:1891–1897.
    233.
    Li X-Z, Mehrotra M, Ghimire S, Adewoye L. 2007. β-Lactam resistance and β-lactamases in bacteria of animal origin. Vet Microbiol 121:197–214.
    234.
    Su LH, Wu TL, Chiu CH. 2012. Development of carbapenem resistance during therapy for non-typhoid Salmonella infection. Clin Microbiol Infect 18:E91–E94.
    235.
    Li L, Liao X, Yang Y, Sun J, Li L, Liu B, Yang S, Ma J, Li X, Zhang Q, Liu Y. 2013. Spread of oqxAB in Salmonella enterica serotype Typhimurium predominantly by IncHI2 plasmids. J Antimicrob Chemother 68:2263–2268.
    236.
    Wong MH, Yan M, Chan EW, Biao K, Chen S. 2014. Emergence of clinical Salmonella enterica serovar Typhimurium isolates with concurrent resistance to ciprofloxacin, ceftriaxone, and azithromycin. Antimicrob Agents Chemother 58:3752–3756.
    237.
    Armand-Lefevre L, Leflon-Guibout V, Bredin J, Barguellil F, Amor A, Pagès JM, Nicolas-Chanoine MH. 2003. Imipenem resistance in Salmonella enterica serovar Wien related to porin loss and CMY-4 β-lactamase production. Antimicrob Agents Chemother 47:1165–1168.
    238.
    Hu WS, Chen HW, Zhang RY, Huang CY, Shen CF. 2011. The expression levels of outer membrane proteins STM1530 and OmpD, which are influenced by the CpxAR and BaeSR two-component systems, play important roles in the ceftriaxone resistance of Salmonella enterica serovar Typhimurium. Antimicrob Agents Chemother 55:3829–3837.
    239.
    Lakey JH, Watts JP, Lea EJ. 1985. Characterisation of channels induced in planar bilayer membranes by detergent solubilised Escherichia coli porins. Biochim Biophys Acta 817:208–216.
    240.
    Navia MM, Ruiz J, Ribera A, de Anta MT, Vila J. 1999. Analysis of the mechanisms of quinolone resistance in clinical isolates of Citrobacter freundii. J Antimicrob Chemother 44:743–748.
    241.
    Tavio M, Vila J, Ruiz J, Amicosante G, Franceschini N, Martin-Sánchez AM, de Anta MT. 2000. In vitro selected fluoroquinolone-resistant mutants of Citrobacter freundii: analysis of the quinolone resistance acquisition. J Antimicrob Chemother 45:521–524.
    242.
    Schumacher A, Trittler R, Bohnert JA, Kummerer K, Pagès J-M, Kern WV. 2007. Intracellular accumulation of linezolid in Escherichia coli, Citrobacter freundii and Enterobacter aerogenes: role of enhanced efflux pump activity and inactivation. J Antimicrob Chemother 59:1261–1264.
    243.
    Dolejska M, Villa L, Poirel L, Nordmann P, Carattoli A. 2013. Complete sequencing of an IncHI1 plasmid encoding the carbapenemase NDM-1, the ArmA 16S RNA methylase and a resistance-nodulation-cell division/multidrug efflux pump. J Antimicrob Chemother 68:34–39.
    244.
    Vu H, Nikaido H. 1985. Role of β-lactam hydrolysis in the mechanism of resistance of a β-lactamase-constitutive Enterobacter cloacae strain to expanded-spectrum β-lactams. Antimicrob Agents Chemother 27:393–398.
    245.
    Masi M, Pagès JM, Villard C, Pradel E. 2005. The eefABC multidrug efflux pump operon is repressed by H-NS in Enterobacter aerogenes. J Bacteriol 187:3894–3897.
    246.
    Charrel RN, Pagès JM, De Micco P, Mallea M. 1996. Prevalence of outer membrane porin alteration in β-lactam-antibiotic-resistant Enterobacter aerogenes. Antimicrob Agents Chemother 40:2854–2858.
    247.
    Lee EH, Nicolas MH, Kitzis MD, Pialoux G, Collatz E, Gutmann L. 1991. Association of two resistance mechanisms in a clinical isolate of Enterobacter cloacae with high-level resistance to imipenem. Antimicrob Agents Chemother 35:1093–1098.
    248.
    Lakaye B, Dubus A, Joris B, Frère JM. 2002. Method for estimation of low outer membrane permeability to β-lactam antibiotics. Antimicrob Agents Chemother 46:2901–2907.
    249.
    Nikaido H, Pagès JM. 2012. Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS Microbiol Rev 36:340–363.
    250.
    Bornet C, Saint N, Fetnaci L, Dupont M, Davin-Regli A, Bollet C, Pagès JM. 2004. Omp35, a new Enterobacter aerogenes porin involved in selective susceptibility to cephalosporins. Antimicrob Agents Chemother 48:2153–2158.
    251.
    Szabo D, Silveira F, Hujer AM, Bonomo RA, Hujer KM, Marsh JW, Bethel CR, Doi Y, Deeley K, Paterson DL. 2006. Outer membrane protein changes and efflux pump expression together may confer resistance to ertapenem in Enterobacter cloacae. Antimicrob Agents Chemother 50:2833–2835.
    252.
    Köhler T, Michea-Hamzehpour M, Epp SF, Pechère JC. 1999. Carbapenem activities against Pseudomonas aeruginosa: respective contributions of OprD and efflux systems. Antimicrob Agents Chemother 43:424–427.
    253.
    Fung-Tomc JC, Gradelski E, Huczko E, Dougherty TJ, Kessler RE, Bonner DP. 1996. Differences in the resistant variants of Enterobacter cloacae selected by extended-spectrum cephalosporins. Antimicrob Agents Chemother 40:1289–1293.
    254.
    Piddock LJ, Traynor EA. 1991. β-Lactamase expression and outer membrane protein changes in cefpirome-resistant and ceftazidime-resistant Gram-negative bacteria. J Antimicrob Chemother 28:209–219.
    255.
    Yang FC, Yan JJ, Hung KH, Wu JJ. 2012. Characterization of ertapenem-resistant Enterobacter cloacae in a Taiwanese university hospital. J Clin Microbiol 50:223–226.
    256.
    Doumith M, Ellington MJ, Livermore DM, Woodford N. 2009. Molecular mechanisms disrupting porin expression in ertapenem-resistant Klebsiella and Enterobacter spp. clinical isolates from the UK. J Antimicrob Chemother 63:659–667.
    257.
    Yigit H, Anderson GJ, Biddle JW, Steward CD, Rasheed JK, Valera LL, McGowan JE, Jr, Tenover FC. 2002. Carbapenem resistance in a clinical isolate of Enterobacter aerogenes is associated with decreased expression of OmpF and OmpC porin analogs. Antimicrob Agents Chemother 46:3817–3822.
    258.
    Lavigne JP, Sotto A, Nicolas-Chanoine MH, Bouziges N, Pagès JM, Davin-Regli A. 2013. An adaptive response of Enterobacter aerogenes to imipenem: regulation of porin balance in clinical isolates. Int J Antimicrob Agents 41:130–136.
    259.
    De E, Basle A, Jaquinod M, Saint N, Mallea M, Molle G, Pagès JM. 2001. A new mechanism of antibiotic resistance in Enterobacteriaceae induced by a structural modification of the major porin. Mol Microbiol 41:189–198.
    260.
    Gayet S, Chollet R, Molle G, Pagès JM, Chevalier J. 2003. Modification of outer membrane protein profile and evidence suggesting an active drug pump in Enterobacter aerogenes clinical strains. Antimicrob Agents Chemother 47:1555–1559.
    261.
    Pradel E, Pagès JM. 2002. The AcrAB-TolC efflux pump contributes to multidrug resistance in the nosocomial pathogen Enterobacter aerogenes. Antimicrob Agents Chemother 46:2640–2643.
    262.
    Chevalier J, Mulfinger C, Garnotel E, Nicolas P, Davin-Regli A, Pagès JM. 2008. Identification and evolution of drug efflux pump in clinical Enterobacter aerogenes strains isolated in 1995 and 2003. PLoS One 3:e3203.
    263.
    Glatz K, Toth A, Paszti J. 2011. The cyclohexane tolerance and Phe-Arg-β-naphtylamide susceptibility of multidrug-resistant Enterobacter cloacae clinical isolates, and the predominance of one PFGE clone in Hungary. Clin Microbiol Infect 17:1254–1261.
    264.
    Pérez A, Poza M, Fernández A, del Carmen Fernández M, Mallo S, Merino M, Rumbo-Feal S, Cabral MP, Bou G. 2012. Involvement of the AcrAB-TolC efflux pump in the resistance, fitness, and virulence of Enterobacter cloacae. Antimicrob Agents Chemother 56:2084–2090.
    265.
    Tran QT, Dupont M, Lavigne JP, Chevalier J, Pagès JM, Sotto A, Davin-Regli A. 2009. Occurrence of efflux mechanism and cephalosporinase variant in a population of Enterobacter aerogenes and Klebsiella pneumoniae isolates producing extended-spectrum β-lactamases. Antimicrob Agents Chemother 53:1652–1656.
    266.
    Chollet R, Chevalier J, Bryskier A, Pagès JM. 2004. The AcrAB-TolC pump is involved in macrolide resistance but not in telithromycin efflux in Enterobacter aerogenes and Escherichia coli. Antimicrob Agents Chemother 48:3621–3624.
    267.
    Hornsey M, Ellington MJ, Doumith M, Scott G, Livermore DM, Woodford N. 2010. Emergence of AcrAB-mediated tigecycline resistance in a clinical isolate of Enterobacter cloacae during ciprofloxacin treatment. Int J Antimicrob Agents 35:478–481.
    268.
    Keeney D, Ruzin A, Bradford PA. 2007. RamA, a transcriptional regulator, and AcrAB, an RND-type efflux pump, are associated with decreased susceptibility to tigecycline in Enterobacter cloacae. Microb Drug Resist 13:1–6.
    269.
    Veleba M, De Majumdar S, Hornsey M, Woodford N, Schneiders T. 2013. Genetic characterization of tigecycline resistance in clinical isolates of Enterobacter cloacae and Enterobacter aerogenes. J Antimicrob Chemother 68:1011–1018.
    270.
    Dutzler R, Rummel G, Alberti S, Hernández-Allés S, Phale P, Rosenbusch J, Benedi V, Schirmer T. 1999. Crystal structure and functional characterization of OmpK36, the osmoporin of Klebsiella pneumoniae. Structure 7:425–434.
    271.
    Doménech-Sánchez A, Martínez-Martínez L, Hernández-Allés S, del Carmen Conejo M, Pascual A, Tomás JM, Alberti S, Benedi VJ. 2003. Role of Klebsiella pneumoniae OmpK35 porin in antimicrobial resistance. Antimicrob Agents Chemother 47:3332–3335.
    272.
    Padilla E, Llobet E, Doménech-Sánchez A, Martínez-Martínez L, Bengoechea JA, Alberti S. 2010. Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance and virulence. Antimicrob Agents Chemother 54:177–183.
    273.
    Gutmann L, Williamson R, Moreau N, Kitzis MD, Collatz E, Acar JF, Goldstein FW. 1985. Cross-resistance to nalidixic acid, trimethoprim, and chloramphenicol associated with alterations in outer membrane proteins of Klebsiella, Enterobacter, and Serratia. J Infect Dis 151:501–507.
    274.
    Pangon B, Bizet C, Bure A, Pichon F, Philippon A, Regnier B, Gutmann L. 1989. In vivo selection of a cephamycin-resistant, porin-deficient mutant of Klebsiella pneumoniae producing a TEM-3 β-lactamase. J Infect Dis 159:1005–1006.
    275.
    Rice LB, Carias LL, Etter L, Shlaes DM. 1993. Resistance to cefoperazone-sulbactam in Klebsiella pneumoniae: evidence for enhanced resistance resulting from the coexistence of two different resistance mechanisms. Antimicrob Agents Chemother 37:1061–1064.
    276.
    Chen HY, Livermore DM. 1993. Activity of cefepime and other β-lactam antibiotics against permeability mutants of Escherichia coli and Klebsiella pneumoniae. J Antimicrob Chemother 32(Suppl B):63–74.
    277.
    Martínez-Martínez L, Hernández-Allés S, Alberti S, Tomás JM, Benedi VJ, Jacoby GA. 1996. In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and expanded-spectrum cephalosporins. Antimicrob Agents Chemother 40:342–348.
    278.
    Ardanuy C, Linares J, Dominguez MA, Hernández-Allés S, Benedi VJ, Martínez-Martínez L. 1998. Outer membrane profiles of clonally related Klebsiella pneumoniae isolates from clinical samples and activities of cephalosporins and carbapenems. Antimicrob Agents Chemother 42:1636–1640.
    279.
    Hernández-Allés S, Benedi VJ, Martínez-Martínez L, Pascual A, Aguilar A, Tomás JM, Alberti S. 1999. Development of resistance during antimicrobial therapy caused by insertion sequence interruption of porin genes. Antimicrob Agents Chemother 43:937–939.
    280.
    Nelson EC, Segal H, Elisha BG. 2003. Outer membrane protein alterations and blaTEM-1 variants: their role in β-lactam resistance in Klebsiella pneumoniae. J Antimicrob Chemother 52:899–903.
    281.
    Doménech-Sánchez A, Pascual A, Suarez AI, Alvarez D, Benedi VJ, Martínez-Martínez L. 2000. Activity of nine antimicrobial agents against clinical isolates of Klebsiella pneumoniae producing extended-spectrum β-lactamases and deficient or not in porins. J Antimicrob Chemother 46:858–859.
    282.
    Jacoby GA, Mills DM, Chow N. 2004. Role of β-lactamases and porins in resistance to ertapenem and other β-lactams in Klebsiella pneumoniae. Antimicrob Agents Chemother 48:3203–3206.
    283.
    Poulou A, Voulgari E, Vrioni G, Koumaki V, Xidopoulos G, Chatzipantazi V, Markou F, Tsakris A. 2013. Outbreak caused by an ertapenem-resistant, CTX-M-15-producing Klebsiella pneumoniae sequence type 101 clone carrying an OmpK36 porin variant. J Clin Microbiol 51:3176–3182.
    284.
    Hernández-Allés S, Conejo M, Pascual A, Tomás JM, Benedi VJ, Martínez-Martínez L. 2000. Relationship between outer membrane alterations and susceptibility to antimicrobial agents in isogenic strains of Klebsiella pneumoniae. J Antimicrob Chemother 46:273–277.
    285.
    Zhang Y, Jiang X, Wang Y, Li G, Tian Y, Liu H, Ai F, Ma Y, Wang B, Ruan F, Rajakumar K. 2014. Contribution of β-lactamases and porin proteins OmpK35 and OmpK36 to carbapenem resistance in clinical isolates of KPC-2-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 58:1214–1217.
    286.
    Rasheed JK, Anderson GJ, Yigit H, Queenan AM, Doménech-Sánchez A, Swenson JM, Biddle JW, Ferraro MJ, Jacoby GA, Tenover FC. 2000. Characterization of the extended-spectrum β-lactamase reference strain, Klebsiella pneumoniae K6 (ATCC 700603), which produces the novel enzyme SHV-18. Antimicrob Agents Chemother 44:2382–2388.
    287.
    Garcia-Fernández A, Miriagou V, Papagiannitsis CC, Giordano A, Venditti M, Mancini C, Carattoli A. 2010. An ertapenem-resistant extended-spectrum-β-lactamase-producing Klebsiella pneumoniae clone carries a novel OmpK36 porin variant. Antimicrob Agents Chemother 54:4178–4184.
    288.
    Wozniak A, Villagra NA, Undabarrena A, Gallardo N, Keller N, Moraga M, Roman JC, Mora GC, Garcia P. 2012. Porin alterations present in non-carbapenemase-producing Enterobacteriaceae with high and intermediate levels of carbapenem resistance in Chile. J Med Microbiol 61:1270–1279.
    289.
    Garcia-Sureda L, Juan C, Doménech-Sánchez A, Alberti S. 2011. Role of Klebsiella pneumoniae LamB porin in antimicrobial resistance. Antimicrob Agents Chemother 55:1803–1805.
    290.
    Ramos PI, Picao RC, Almeida LG, Lima NC, Girardello R, Vivan AC, Xavier DE, Barcellos FG, Pelisson M, Vespero EC, Medigue C, Vasconcelos AT, Gales AC, Nicolas MF. 2014. Comparative analysis of the complete genome of KPC-2-producing Klebsiella pneumoniae Kp13 reveals remarkable genome plasticity and a wide repertoire of virulence and resistance mechanisms. BMC Genomics 15:54.
    291.
    Mazzariol A, Zuliani J, Cornaglia G, Rossolini GM, Fontana R. 2002. AcrAB efflux system: expression and contribution to fluoroquinolone resistance in Klebsiella spp. Antimicrob Agents Chemother 46:3984–3986.
    292.
    Schneiders T, Amyes SG, Levy SB. 2003. Role of AcrR and ramA in fluoroquinolone resistance in clinical Klebsiella pneumoniae isolates from Singapore. Antimicrob Agents Chemother 47:2831–2837.
    293.
    Chevalier J, Pagès JM, Eyraud A, Mallea M. 2000. Membrane permeability modifications are involved in antibiotic resistance in Klebsiella pneumoniae. Biochem Biophys Res Commun 274:496–499.
    294.
    Gruteke P, Goessens W, Van Gils J, Peerbooms P, Lemmens-Den Toom N, Van Santen-Verheuvel M, Van Belkum A, Verbrugh H. 2003. Patterns of resistance associated with integrons, the extended-spectrum β-lactamase SHV-5 gene, and a multidrug efflux pump of Klebsiella pneumoniae causing a nosocomial outbreak. J Clin Microbiol 41:1161–1166.
    295.
    Martínez-Martínez L, Pascual A, del Carmen Conejo M, Garcia I, Joyanes P, Doménech-Sánchez A, Benedi VJ. 2002. Energy-dependent accumulation of norfloxacin and porin expression in clinical isolates of Klebsiella pneumoniae and relationship to extended-spectrum β-lactamase production. Antimicrob Agents Chemother 46:3926–3932.
    296.
    Pagès JM, Lavigne JP, Leflon-Guibout V, Marcon E, Bert F, Noussair L, Nicolas-Chanoine MH. 2009. Efflux pump, the masked side of β-lactam resistance in Klebsiella pneumoniae clinical isolates. PLoS One 4:e4817.
    297.
    Källman O, Motakefi A, Wretlind B, Kalin M, Olsson-Liljequist B, Giske CG. 2008. Cefuroxime non-susceptibility in multidrug-resistant Klebsiella pneumoniae overexpressing ramA and acrA and expressing ompK35 at reduced levels. J Antimicrob Chemother 62:986–990.
    298.
    Källman O, Giske CG, Samuelsen O, Wretlind B, Kalin M, Olsson-Liljequist B. 2009. Interplay of efflux, impermeability, and AmpC activity contributes to cefuroxime resistance in clinical, non-ESBL-producing isolates of Escherichia coli. Microb Drug Resist 15:91–95.
    299.
    Bialek-Davenet S, Marcon E, Leflon-Guibout V, Lavigne JP, Bert F, Moreau R, Nicolas-Chanoine MH. 2011. In vitro selection of ramR and soxR mutants overexpressing efflux systems by fluoroquinolones as well as cefoxitin in Klebsiella pneumoniae. Antimicrob Agents Chemother 55:2795–2802.
    300.
    Villa L, Feudi C, Fortini D, Garcia-Fernández A, Carattoli A. 2014. Genomics of KPC-producing Klebsiella pneumoniae sequence type 512 clone highlights the role of RamR and ribosomal S10 protein mutations in conferring tigecycline resistance. Antimicrob Agents Chemother 58:1707–1712.
    301.
    Sheng ZK, Hu F, Wang W, Guo Q, Chen Z, Xu X, Zhu D, Wang M. 2014. Mechanisms of tigecycline resistance among Klebsiella pneumoniae clinical isolates. Antimicrob Agents Chemother 58:6982–6985.
    302.
    Kim HB, Wang M, Park CH, Kim EC, Jacoby GA, Hooper DC. 2009. oqxAB encoding a multidrug efflux pump in human clinical isolates of Enterobacteriaceae. Antimicrob Agents Chemother 53:3582–3584.
    303.
    Pérez F, Rudin SD, Marshall SH, Coakley P, Chen L, Kreiswirth BN, Rather PN, Hujer AM, Toltzis P, van Duin D, Paterson DL, Bonomo RA. 2013. OqxAB, a quinolone and olaquindox efflux pump, is widely distributed among multidrug-resistant Klebsiella pneumoniae isolates of human origin. Antimicrob Agents Chemother 57:4602–4603.
    304.
    Kumar V, Sun P, Vamathevan J, Li Y, Ingraham K, Palmer L, Huang J, Brown JR. 2011. Comparative genomics of Klebsiella pneumoniae strains with different antibiotic resistance profiles. Antimicrob Agents Chemother 55:4267–4276.
    305.
    Nielsen LE, Snesrud EC, Onmus-Leone F, Kwak YI, Aviles R, Steele ED, Sutter DE, Waterman PE, Lesho EP. 2014. IS5 element integration, a novel mechanism for rapid in vivo emergence of tigecycline nonsusceptibility in Klebsiella pneumoniae. Antimicrob Agents Chemother 58:6151–6156.
    306.
    Ogawa W, Onishi M, Ni R, Tsuchiya T, Kuroda T. 2012. Functional study of the novel multidrug efflux pump KexD from Klebsiella pneumoniae. Gene 498:177–182.
    307.
    Srinivasan VB, Singh BB, Priyadarshi N, Chauhan NK, Rajamohan G. 2014. Role of novel multidrug efflux pump involved in drug resistance in Klebsiella pneumoniae. PLoS One 9:e96288.
    308.
    Mitsuyama J, Hiruma R, Yamaguchi A, Sawai T. 1987. Identification of porins in outer membrane of Proteus, Morganella, and Providencia spp. and their role in outer membrane permeation of β-lactams. Antimicrob Agents Chemother 31:379–384.
    309.
    Tavio MM, Vila J, Ruiz J, Martin Sánchez AM, Jimenez de Anta MT. 2000. Decreased permeability and enhanced proton-dependent active efflux in the development of resistance to quinolones in Morganella morganii. Int J Antimicrob Agents 14:157–160.
    310.
    Visalli MA, Murphy E, Projan SJ, Bradford PA. 2003. AcrAB multidrug efflux pump is associated with reduced levels of susceptibility to tigecycline (GAR-936) in Proteus mirabilis. Antimicrob Agents Chemother 47:665–669.
    311.
    Saito R, Sato K, Kumita W, Inami N, Nishiyama H, Okamura N, Moriya K, Koike K. 2006. Role of type II topoisomerase mutations and AcrAB efflux pump in fluoroquinolone-resistant clinical isolates of Proteus mirabilis. J Antimicrob Chemother 58:673–677.
    312.
    Ruzin A, Keeney D, Bradford PA. 2005. AcrAB efflux pump plays a role in decreased susceptibility to tigecycline in Morganella morganii. Antimicrob Agents Chemother 49:791–793.
    313.
    Mitsuyama J, Itoh Y, Takahata M, Okamoto S, Yasuda T. 1992. In vitro antibacterial activities of tosufloxacin against and uptake of tosufloxacin by outer membrane mutants of Escherichia coli, Proteus mirabilis, and Salmonella typhimurium. Antimicrob Agents Chemother 36:2030–2036.
    314.
    Kadavy DR, Hornby JM, Haverkost T, Nickerson KW. 2000. Natural antibiotic resistance of bacteria isolated from larvae of the oil fly, Helaeomyia petrolei. Appl Environ Microbiol 66:4615–4619.
    315.
    Hutsul JA, Worobec E. 1997. Molecular characterization of the Serratia marcescens OmpF porin, and analysis of S. marcescens OmpF and OmpC osmoregulation. Microbiology 143:2797–2806.
    316.
    Gutmann L, Chabbert YA. 1984. Different mechanisms of resistance to latamoxef (moxalactam) in Serratia marcescens. J Antimicrob Chemother 13:15–22.
    317.
    Weindorf H, Schmidt H, Martin HH. 1998. Contribution of overproduced chromosomal β-lactamase and defective outer membrane porins to resistance to extended-spectrum β-lactam antibiotics in Serratia marcescens. J Antimicrob Chemother 41:189–195.
    318.
    Ruiz N, Montero T, Hernandez-Borrell J, Vinas M. 2003. The role of Serratia marcescens porins in antibiotic resistance. Microb Drug Resist 9:257–264.
    319.
    Berlanga M, Vinas M. 2000. Salicylate induction of phenotypic resistance to quinolones in Serratia marcescens. J Antimicrob Chemother 46:279–282.
    320.
    Kumar A, Worobec EA. 2005. Cloning, sequencing, and characterization of the SdeAB multidrug efflux pump of Serratia marcescens. Antimicrob Agents Chemother 49:1495–1501.
    321.
    Begic S, Worobec EA. 2008. The role of the Serratia marcescens SdeAB multidrug efflux pump and TolC homologue in fluoroquinolone resistance studied via gene-knockout mutagenesis. Microbiology 154:454–461.
    322.
    Maseda H, Hashida Y, Konaka R, Shirai A, Kourai H. 2009. Mutational upregulation of a resistance-nodulation-cell division-type multidrug efflux pump, SdeAB, upon exposure to a biocide, cetylpyridinium chloride, and antibiotic resistance in Serratia marcescens. Antimicrob Agents Chemother 53:5230–5235.
    323.
    Maseda H, Hashida Y, Shirai A, Omasa T, Nakae T. 2011. Mutation in the sdeS gene promotes expression of the sdeAB efflux pump genes and multidrug resistance in Serratia marcescens. Antimicrob Agents Chemother 55:2922–2926.
    324.
    Hornsey M, Ellington MJ, Doumith M, Hudson S, Livermore DM, Woodford N. 2010. Tigecycline resistance in Serratia marcescens associated with up-regulation of the SdeXY-HasF efflux system also active against ciprofloxacin and cefpirome. J Antimicrob Chemother 65:479–482.
    325.
    Dalvi SD, Worobec EA. 2012. Gene expression analysis of the SdeAB multidrug efflux pump in antibiotic-resistant clinical isolates of Serratia marcescens. Indian J Med Microbiol 30:302–307.
    326.
    Yang H, Duan G, Zhu J, Lv R, Xi Y, Zhang W, Fan Q, Zhang M. 2008. The AcrAB-TolC pump is involved in multidrug resistance in clinical Shigella flexneri isolates. Microb Drug Resist 14:245–249.
    327.
    Azmi IJ, Khajanchi BK, Akter F, Hasan TN, Shahnaij M, Akter M, Banik A, Sultana H, Hossain MA, Ahmed MK, Faruque SM, Talukder KA. 2014. Fluoroquinolone resistance mechanisms of Shigella flexneri isolated in Bangladesh. PLoS One 9:e102533.
    328.
    Kim JY, Jeon SM, Kim H, Park MS, Kim SH. 2011. A contribution of MdfA to resistance to fluoroquinolones in Shigella flexneri. Osong Public Health Res Perspect 2:216–217.
    329.
    Brzostek K, Nichols WW. 1990. Outer membrane permeability and porin proteins of Yersinia enterocolitica. FEMS Microbiol Lett 58:275–277.
    330.
    Capilla S, Ruiz J, Goni P, Castillo J, Rubio MC, Jimenez de Anta MT, Gomez-Lus R, Vila J. 2004. Characterization of the molecular mechanisms of quinolone resistance in Yersinia enterocolitica O:3 clinical isolates. J Antimicrob Chemother 53:1068–1071.
    331.
    Udani RA, Levy SB. 2006. MarA-like regulator of multidrug resistance in Yersinia pestis. Antimicrob Agents Chemother 50:2971–2975.
    332.
    Stirrett KL, Ferreras JA, Rossi SM, Moy RL, Fonseca FV, Quadri LE. 2008. A multicopy suppressor screening approach as a means to identify antibiotic resistance determinant candidates in Yersinia pestis. BMC Microbiol 8:122.
    333.
    Lister IM, Raftery C, Mecsas J, Levy SB. 2012. Yersinia pestis AcrAB-TolC in antibiotic resistance and virulence. Antimicrob Agents Chemother 56:1120–1123.
    334.
    Bengoechea JA, Skurnik M. 2000. Temperature-regulated efflux pump/potassium antiporter system mediates resistance to cationic antimicrobial peptides in Yersinia. Mol Microbiol 37:67–80.
    335.
    Paul S, Chaudhuri K, Chatterjee AN, Das J. 1992. Presence of exposed phospholipids in the outer membrane of Vibrio cholerae. J Gen Microbiol 138:755–761.
    336.
    Dalsgaard A, Serichantalergs O, Pitarangsi C, Echeverria P. 1995. Molecular characterization and antibiotic susceptibility of Vibrio cholerae non-O1. Epidemiol Infect 114:51–63.
    337.
    Benz R, Maier E, Chakraborty T. 1997. Purification of OmpU from Vibrio cholerae classical strain 569B: evidence for the formation of large cation-selective ion-permeable channels by OmpU. Microbiologia 13:321–330.
    338.
    Chakrabarti SR, Chaudhuri K, Sen K, Das J. 1996. Porins of Vibrio cholerae: purification and characterization of OmpU. J Bacteriol 178:524–530.
    339.
    Pagel M, Delcour AH. 2011. Effects of conjugated and unconjugated bile acids on the activity of the Vibrio cholerae porin OmpT. Mol Membr Biol 28:69–78.
    340.
    Bina JE, Provenzano D, Wang C, Bina XR, Mekalanos JJ. 2006. Characterization of the Vibrio cholerae vexAB and vexCD efflux systems. Arch Microbiol 186:171–181.
    341.
    Bina XR, Provenzano D, Nguyen N, Bina JE. 2008. Vibrio cholerae RND family efflux systems are required for antimicrobial resistance, optimal virulence factor production, and colonization of the infant mouse small intestine. Infect Immun 76:3595–3605.
    342.
    Cerda-Maira FA, Ringelberg CS, Taylor RK. 2008. The bile response repressor, BreR, regulates expression of the Vibrio cholerae breAB efflux system operon. J Bacteriol 190:7441–7452.
    343.
    Rahman MM, Matsuo T, Ogawa W, Koterasawa M, Kuroda T, Tsuchiya T. 2007. Molecular cloning and characterization of all RND-type efflux transporters in Vibrio cholerae non-O1. Microbiol Immunol 51:1061–1070.
    344.
    Taylor DL, Bina XR, Bina JE. 2012. Vibrio cholerae VexH encodes a multiple drug efflux pump that contributes to the production of cholera toxin and the toxin co-regulated pilus. PLoS One 7:e38208.
    345.
    Taylor DL, Bina XR, Slamti L, Waldor MK, Bina JE. 2014. Reciprocal regulation of RND efflux systems and the Cpx two-component system in Vibrio cholerae. Infect Immun 82:2980–2991.
    346.
    Bina XR, Philippart JA, Bina JE. 2009. Effect of the efflux inhibitors 1-(1-naphthylmethyl)-piperazine and phenyl-arginine-β-naphthylamide on antimicrobial susceptibility and virulence factor production in Vibrio cholerae. J Antimicrob Chemother 63:103–108.
    347.
    Matsuo T, Hayashi K, Morita Y, Koterasawa M, Ogawa W, Mizushima T, Tsuchiya T, Kuroda T. 2007. VmeAB, an RND-type multidrug efflux transporter in Vibrio parahaemolyticus. Microbiology 153:4129–4137.
    348.
    Matsuo T, Nakamura K, Kodama T, Mikami T, Hiyoshi H, Tsuchiya T, Ogawa W, Kuroda T. 2013. Characterization of all RND-type multidrug efflux transporters in Vibrio parahaemolyticus. Microbiologyopen 2:725–742.
    349.
    Matsuo T, Ogawa W, Tsuchiya T, Kuroda T. 2014. Overexpression of vmeTUV encoding a multidrug efflux transporter of Vibrio parahaemolyticus causes bile acid resistance. Gene 541:19–25.
    350.
    Colmer JA, Fralick JA, Hamood AN. 1998. Isolation and characterization of a putative multidrug resistance pump from Vibrio cholerae. Mol Microbiol 27:63–72.
    351.
    Smith KP, Kumar S, Varela MF. 2009. Identification, cloning, and functional characterization of EmrD-3, a putative multidrug efflux pump of the major facilitator superfamily from Vibrio cholerae O395. Arch Microbiol 191:903–911.
    352.
    Chen S, Wang H, Katzianer DS, Zhong Z, Zhu J. 2013. LysR family activator-regulated major facilitator superfamily transporters are involved in Vibrio cholerae antimicrobial compound resistance and intestinal colonisation. Int J Antimicrob Agents 41:188–192.
    353.
    Morita Y, Kodama K, Shiota S, Mine T, Kataoka A, Mizushima T, Tsuchiya T. 1998. NorM, a putative multidrug efflux protein, of Vibrio parahaemolyticus and its homolog in Escherichia coli. Antimicrob Agents Chemother 42:1778–1782.
    354.
    Mohanty P, Patel A, Kushwaha Bhardwaj A. 2012. Role of H- and D-MATE-type transporters from multidrug resistant clinical isolates of Vibrio fluvialis in conferring fluoroquinolone resistance. PLoS One 7:e35752.
    355.
    Lutwyche P, Exner MM, Hancock RE, Trust TJ. 1995. A conserved Aeromonas salmonicida porin provides protective immunity to rainbow trout. Infect Immun 63:3137–3142.
    356.
    Cruz A, Micaelo N, Felix V, Song JY, Kitamura S, Suzuki S, Mendo S. 2013. sugE: a gene involved in tributyltin (TBT) resistance of Aeromonas molluscorum Av27. J Gen Appl Microbiol 59:39–47.
    357.
    Alcaide E, Blasco MD, Esteve C. 2010. Mechanisms of quinolone resistance in Aeromonas species isolated from humans, water and eels. Res Microbiol 161:40–45.
    358.
    Gabay JE, Blake M, Niles WD, Horwitz MA. 1985. Purification of Legionella pneumophila major outer membrane protein and demonstration that it is a porin. J Bacteriol 162:85–91.
    359.
    Bruin JP, Ijzerman EP, den Boer JW, Mouton JW, Diederen BM. 2012. Wild-type MIC distribution and epidemiological cut-off values in clinical Legionella pneumophila serogroup 1 isolates. Diagn Microbiol Infect Dis 72:103–108.
    360.
    Nielsen K, Bangsborg JM, Hoiby N. 2000. Susceptibility of Legionella species to five antibiotics and development of resistance by exposure to erythromycin, ciprofloxacin, and rifampicin. Diagn Microbiol Infect Dis 36:43–48.
    361.
    Almahmoud I, Kay E, Schneider D, Maurin M. 2009. Mutational paths towards increased fluoroquinolone resistance in Legionella pneumophila. J Antimicrob Chemother 64:284–293.
    362.
    Chien M, Morozova I, Shi S, Sheng H, Chen J, Gomez SM, Asamani G, Hill K, Nuara J, Feder M, Rineer J, Greenberg JJ, Steshenko V, Park SH, Zhao B, Teplitskaya E, Edwards JR, Pampou S, Georghiou A, Chou IC, Iannuccilli W, Ulz ME, Kim DH, Geringer-Sameth A, Goldsberry C, Morozov P, Fischer SG, Segal G, Qu X, Rzhetsky A, Zhang P, Cayanis E, De Jong PJ, Ju J, Kalachikov S, Shuman HA, Russo JJ. 2004. The genomic sequence of the accidental pathogen Legionella pneumophila. Science 305:1966–1968.
    363.
    Ferhat M, Atlan D, Vianney A, Lazzaroni JC, Doublet P, Gilbert C. 2009. The TolC protein of Legionella pneumophila plays a major role in multi-drug resistance and the early steps of host invasion. PLoS One 4:e7732.
    364.
    Luo Y, Glisson JR, Jackwood MW, Hancock RE, Bains M, Cheng IH, Wang C. 1997. Cloning and characterization of the major outer membrane protein gene (ompH) of Pasteurella multocida X-73. J Bacteriol 179:7856–7864.
    365.
    Chevalier G, Duclohier H, Thomas D, Shechter E, Wroblewski H. 1993. Purification and characterization of protein H, the major porin of Pasteurella multocida. J Bacteriol 175:266–276.
    366.
    Hatfaludi T, Al-Hasani K, Dunstone M, Boyce J, Adler B. 2008. Characterization of TolC efflux pump proteins from Pasteurella multocida. Antimicrob Agents Chemother 52:4166–4171.
    367.
    Michael GB, Eidam C, Kadlec K, Meyer K, Sweeney MT, Murray RW, Watts JL, Schwarz S. 2012. Increased MICs of gamithromycin and tildipirosin in the presence of the genes erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia haemolytica. J Antimicrob Chemother 67:1555–1557.
    368.
    Vachon V, Lyew DJ, Coulton JW. 1985. Transmembrane permeability channels across the outer membrane of Haemophilus influenzae type b. J Bacteriol 162:918–924.
    369.
    Burns JL, Smith AL. 1987. A major outer-membrane protein functions as a porin in Haemophilus influenzae. J Gen Microbiol 133:1273–1277.
    370.
    Sánchez L, Pan W, Vinas M, Nikaido H. 1997. The acrAB homolog of Haemophilus influenzae codes for a functional multidrug efflux pump. J Bacteriol 179:6855–6857.
    371.
    Trepod CM, Mott JE. 2004. Identification of the Haemophilus influenzae tolC gene by susceptibility profiles of insertionally inactivated efflux pump mutants. Antimicrob Agents Chemother 48:1416–1418.
    372.
    Peric M, Bozdogan B, Jacobs MR, Appelbaum PC. 2003. Effects of an efflux mechanism and ribosomal mutations on macrolide susceptibility of Haemophilus influenzae clinical isolates. Antimicrob Agents Chemother 47:1017–1022.
    373.
    Garcia-Cobos S, Campos J, Lazaro E, Roman F, Cercenado E, Garcia-Rey C, Pérez-Vazquez M, Oteo J, de Abajo F. 2007. Ampicillin-resistant non-β-lactamase-producing Haemophilus influenzae in Spain: recent emergence of clonal isolates with increased resistance to cefotaxime and cefixime. Antimicrob Agents Chemother 51:2564–2573.
    374.
    Dean CR, Narayan S, Daigle DM, Dzink-Fox JL, Puyang X, Bracken KR, Dean KE, Weidmann B, Yuan Z, Jain R, Ryder NS. 2005. Role of the AcrAB-TolC efflux pump in determining susceptibility of Haemophilus influenzae to the novel peptide deformylase inhibitor LBM415. Antimicrob Agents Chemother 49:3129–3135.
    375.
    Livermore DM, Davy KW. 1991. Invalidity for Pseudomonas aeruginosa of an accepted model of bacterial permeability to β-lactam antibiotics. Antimicrob Agents Chemother 35:916–921.
    376.
    Pumbwe L, Everett MJ, Hancock RE, Piddock LJ. 1996. Role of gyrA mutation and loss of OprF in the multiple antibiotic resistance phenotype of Pseudomonas aeruginosa G49. FEMS Microbiol Lett 143:25–28.
    377.
    Pumbwe L, Piddock LJ. 2000. Two efflux systems expressed simultaneously in multidrug-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 44:2861–2864.
    378.
    Bratu S, Landman D, Gupta J, Quale J. 2007. Role of AmpD, OprF and penicillin-binding proteins in β-lactam resistance in clinical isolates of Pseudomonas aeruginosa. J Med Microbiol 56:809–814.
    379.
    Trias J, Nikaido H. 1990. Outer membrane protein D2 catalyzes facilitated diffusion of carbapenems and penems through the outer membrane of Pseudomonas aeruginosa. Antimicrob Agents Chemother 34:52–57.
    380.
    Quale J, Bratu S, Gupta J, Landman D. 2006. Interplay of efflux system, ampC, and oprD expression in carbapenem resistance of Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother 50:1633–1641.
    381.
    Gutierrez O, Juan C, Cercenado E, Navarro F, Bouza E, Coll P, Pérez JL, Oliver A. 2007. Molecular epidemiology and mechanisms of carbapenem resistance in Pseudomonas aeruginosa isolates from Spanish hospitals. Antimicrob Agents Chemother 51:4329–4335.
    382.
    Tomás M, Doumith M, Warner M, Turton JF, Beceiro A, Bou G, Livermore DM, Woodford N. 2010. Efflux pumps, OprD porin, AmpC β-lactamase, and multiresistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Antimicrob Agents Chemother 54:2219–2224.
    383.
    Riera E, Cabot G, Mulet X, Garcia-Castillo M, del Campo R, Juan C, Canton R, Oliver A. 2011. Pseudomonas aeruginosa carbapenem resistance mechanisms in Spain: impact on the activity of imipenem, meropenem and doripenem. J Antimicrob Chemother 66:2022–2027.
    384.
    Fournier D, Richardot C, Muller E, Robert-Nicoud M, Llanes C, Plésiat P, Jeannot K. 2013. Complexity of resistance mechanisms to imipenem in intensive care unit strains of Pseudomonas aeruginosa. J Antimicrob Chemother 68:1772–1780.
    385.
    Xavier DE, Picao RC, Girardello R, Fehlberg LC, Gales AC. 2010. Efflux pumps expression and its association with porin down-regulation and β-lactamase production among Pseudomonas aeruginosa causing bloodstream infections in Brazil. BMC Microbiol 10:217.
    386.
    Dieppois G, Ducret V, Caille O, Perron K. 2012. The transcriptional regulator CzcR modulates antibiotic resistance and quorum sensing in Pseudomonas aeruginosa. PLoS One 7:e38148.
    387.
    Wang D, Seeve C, Pierson LS, III, Pierson EA. 2013. Transcriptome profiling reveals links between ParS/ParR, MexEF-OprN, and quorum sensing in the regulation of adaptation and virulence in Pseudomonas aeruginosa. BMC Genomics 14:618.
    388.
    Poole K, Heinrichs DE, Neshat S. 1993. Cloning and sequence analysis of an EnvCD homologue in Pseudomonas aeruginosa: regulation by iron and possible involvement in the secretion of the siderophore pyoverdine. Mol Microbiol 10:529–544.
    389.
    Masuda N, Ohya S. 1992. Cross-resistance to meropenem, cephems, and quinolones in Pseudomonas aeruginosa. Antimicrob Agents Chemother 36:1847–1851.
    390.
    Li X-Z, Zhang L, Srikumar R, Poole K. 1998. β-Lactamase inhibitors are substrates for the multidrug efflux pumps of Pseudomonas aeruginosa. Antimicrob Agents Chemother 42:399–403.
    391.
    Nakae T, Saito K, Nakajima A. 2000. Effect of sulbactam on anti-pseudomonal activity of β-lactam antibiotics in cells producing various levels of the MexAB-OprM efflux pump and β-lactamase. Microbiol Immunol 44:997–1001.
    392.
    Zhang L, Li XZ, Poole K. 2001. Fluoroquinolone susceptibilities of efflux-mediated multidrug-resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Burkholderia cepacia. J Antimicrob Chemother 48:549–552.
    393.
    Dean CR, Visalli MA, Projan SJ, Sum PE, Bradford PA. 2003. Efflux-mediated resistance to tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1. Antimicrob Agents Chemother 47:972–978.
    394.
    Dupont P, Hocquet D, Jeannot K, Chavanet P, Plésiat P. 2005. Bacteriostatic and bactericidal activities of eight fluoroquinolones against MexAB-OprM-overproducing clinical strains of Pseudomonas aeruginosa. J Antimicrob Chemother 55:518–522.
    395.
    Papadopoulos CJ, Carson CF, Chang BJ, Riley TV. 2008. Role of the MexAB-OprM efflux pump of Pseudomonas aeruginosa in tolerance to tea tree (Melaleuca alternifolia) oil and its monoterpene components terpinen-4-ol, 1,8-cineole, and alpha-terpineol. Appl Environ Microbiol 74:1932–1935.
    396.
    Robertson GT, Doyle TB, Du Q, Duncan L, Mdluli KE, Lynch AS. 2007. A novel indole compound that inhibits Pseudomonas aeruginosa growth by targeting MreB is a substrate for MexAB-OprM. J Bacteriol 189:6870–6881.
    397.
    Li X-Z, Zhang L, Poole K. 1998. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol 180:2987–2991.
    398.
    Evans K, Passador L, Srikumar R, Tsang E, Nezezon J, Poole K. 1998. Influence of the MexAB-OprM multidrug efflux system on quorum sensing in Pseudomonas aeruginosa. J Bacteriol 180:5443–5447.
    399.
    Pearson JP, Van Delden C, Iglewski BH. 1999. Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals. J Bacteriol 181:1203–1210.
    400.
    Minagawa S, Inami H, Kato T, Sawada S, Yasuki T, Miyairi S, Horikawa M, Okuda J, Gotoh N. 2012. RND type efflux pump system MexAB-OprM of Pseudomonas aeruginosa selects bacterial languages, 3-oxo-acyl-homoserine lactones, for cell-to-cell communication. BMC Microbiol 12:70.
    401.
    Moore JD, Gerdt JP, Eibergen NR, Blackwell HE. 2014. Active efflux influences the potency of quorum sensing inhibitors in Pseudomonas aeruginosa. Chembiochem 15:435–442.
    402.
    Masuda N, Sakagawa E, Ohya S. 1995. Outer membrane proteins responsible for multiple drug resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 39:645–649.
    403.
    Poole K, Tetro K, Zhao Q, Neshat S, Heinrichs DE, Bianco N. 1996. Expression of the multidrug resistance operon mexA-mexB-oprM in Pseudomonas aeruginosa: mexR encodes a regulator of operon expression. Antimicrob Agents Chemother 40:2021–2028.
    404.
    Srikumar R, Paul CJ, Poole K. 2000. Influence of mutations in the mexR repressor gene on expression of the MexA-MexB-OprM multidrug efflux system of Pseudomonas aeruginosa. J Bacteriol 182:1410–1414.
    405.
    Adewoye L, Sutherland A, Srikumar R, Poole K. 2002. The mexR repressor of the mexAB-oprM multidrug efflux operon in Pseudomonas aeruginosa: characterization of mutations compromising activity. J Bacteriol 184:4308–4312.
    406.
    Cao L, Srikumar R, Poole K. 2004. MexAB-OprM hyperexpression in NalC-type multidrug-resistant Pseudomonas aeruginosa: identification and characterization of the nalC gene encoding a repressor of PA3720-PA3719. Mol Microbiol 53:1423–1436.
    407.
    Saito K, Akama H, Yoshihara E, Nakae T. 2003. Mutations affecting DNA-binding activity of the MexR repressor of mexR-mexA-mexB-oprM operon expression. J Bacteriol 185:6195–6198.
    408.
    Sobel ML, Hocquet D, Cao L, Plésiat P, Poole K. 2005. Mutations in PA3574 (nalD) lead to increased MexAB-OprM expression and multidrug resistance in laboratory and clinical isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother 49:1782–1786.
    409.
    Andrésen C, Jalal S, Aili D, Wang Y, Islam S, Jarl A, Liedberg B, Wretlind B, Martensson LG, Sunnerhagen M. 2010. Critical biophysical properties in the Pseudomonas aeruginosa efflux gene regulator MexR are targeted by mutations conferring multidrug resistance. Protein Sci 19:680–692.
    410.
    Hamzehpour MM, Pechère JC, Plésiat P, Köhler T. 1995. OprK and OprM define two genetically distinct multidrug efflux systems in Pseudomonas aeruginosa. Antimicrob Agents Chemother 39:2392–2396.
    411.
    Lomovskaya O, Lee A, Hoshino K, Ishida H, Mistry A, Warren MS, Boyer E, Chamberland S, Lee VJ. 1999. Use of a genetic approach to evaluate the consequences of inhibition of efflux pumps in Pseudomonas aeruginosa. Antimicrob Agents Chemother 43:1340–1346.
    412.
    Hocquet D, Bertrand X, Köhler T, Talon D, Plésiat P. 2003. Genetic and phenotypic variations of a resistant Pseudomonas aeruginosa epidemic clone. Antimicrob Agents Chemother 47:1887–1894.
    413.
    Llanes C, Hocquet D, Vogne C, Benali-Baitich D, Neuwirth C, Plésiat P. 2004. Clinical strains of Pseudomonas aeruginosa overproducing MexAB-OprM and MexXY efflux pumps simultaneously. Antimicrob Agents Chemother 48:1797–1802.
    414.
    Henrichfreise B, Wiegand I, Pfister W, Wiedemann B. 2007. Resistance mechanisms of multiresistant Pseudomonas aeruginosa strains from Germany and correlation with hypermutation. Antimicrob Agents Chemother 51:4062–4070.
    415.
    Cavallo JD, Hocquet D, Plésiat P, Fabre R, Roussel-Delvallez M, GERPA. 2007. Susceptibility of Pseudomonas aeruginosa to antimicrobials: a 2004 French multicentre hospital study. J Antimicrob Chemother 59:1021–1024.
    416.
    Cabot G, Ocampo-Sosa AA, Dominguez MA, Gago JF, Juan C, Tubau F, Rodríguez C, Moya B, Pena C, Martínez-Martínez L, Oliver A, Spanish Network for Research in Infectious Diseases. 2012. Genetic markers of widespread extensively drug-resistant Pseudomonas aeruginosa high-risk clones. Antimicrob Agents Chemother 56:6349–6357.
    417.
    Moya B, Beceiro A, Cabot G, Juan C, Zamorano L, Alberti S, Oliver A. 2012. Pan-β-lactam resistance development in Pseudomonas aeruginosa clinical strains: molecular mechanisms, penicillin-binding protein profiles, and binding affinities. Antimicrob Agents Chemother 56:4771–4778.
    418.
    Li X-Z. 2012. Multidrug resistance efflux pumps of Pseudomonas aeruginosa: a 10-year update. Chin J Antibiot 37:481–500.
    419.
    Sacha P, Wieczorek P, Ojdana D, Hauschild T, Milewski R, Czaban S, Poniatowski B, Tryniszewska E. 2014. Expression of MexAB-OprM efflux pump system and susceptibility to antibiotics of different Pseudomonas aeruginosa clones isolated from patients hospitalized in two intensive care units at University Hospital in Bialystok (northeastern Poland) between January 2002 and December 2009. APMIS 122:931–940.
    420.
    Pournaras S, Maniati M, Spanakis N, Ikonomidis A, Tassios PT, Tsakris A, Legakis NJ, Maniatis AN. 2005. Spread of efflux pump-overexpressing, non-metallo-β-lactamase-producing, meropenem-resistant but ceftazidime-susceptible Pseudomonas aeruginosa in a region with blaVIM endemicity. J Antimicrob Chemother 56:761–764.
    421.
    Castanheira M, Deshpande LM, Costello A, Davies TA, Jones RN. 2014. Epidemiology and carbapenem resistance mechanisms of carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009-11 in 14 European and Mediterranean countries. J Antimicrob Chemother 69:1804–1814.
    422.
    Fehlberg LC, Xavier DE, Peraro PP, Marra AR, Edmond MB, Gales AC. 2012. β-Lactam resistance mechanisms in Pseudomonas aeruginosa strains causing bloodstream infections: comparative results between Brazilian and American isolates. Microb Drug Resist 18:402–407.
    423.
    Hocquet D, Roussel-Delvallez M, Cavallo JD, Plésiat P. 2007. MexAB-OprM- and MexXY-overproducing mutants are very prevalent among clinical strains of Pseudomonas aeruginosa with reduced susceptibility to ticarcillin. Antimicrob Agents Chemother 51:1582–1583.
    424.
    Kriengkauykiat J, Porter E, Lomovskaya O, Wong-Beringer A. 2005. Use of an efflux pump inhibitor to determine the prevalence of efflux pump-mediated fluoroquinolone resistance and multidrug resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 49:565–570.
    425.
    Campo Esquisabel AB, Rodríguez MC, Campo-Sosa AO, Rodríguez C, Martínez-Martínez L. 2011. Mechanisms of resistance in clinical isolates of Pseudomonas aeruginosa less susceptible to cefepime than to ceftazidime. Clin Microbiol Infect 17:1817–1822.
    426.
    Ziha-Zarifi I, Llanes C, Köhler T, Pechère JC, Plésiat P. 1999. In vivo emergence of multidrug-resistant mutants of Pseudomonas aeruginosa overexpressing the active efflux system MexA-MexB-OprM. Antimicrob Agents Chemother 43:287–291.
    427.
    Ong CT, Tessier PR, Li C, Nightingale CH, Nicolau DP. 2007. Comparative in vivo efficacy of meropenem, imipenem, and cefepime against Pseudomonas aeruginosa expressing MexA-MexB-OprM efflux pumps. Diagn Microbiol Infect Dis 57:153–161.
    428.
    Boutoille D, Jacqueline C, Le Mabecque V, Potel G, Caillon J. 2009. In vivo impact of the MexAB-OprM efflux system on β-lactam efficacy in an experimental model of Pseudomonas aeruginosa infection. Int J Antimicrob Agents 33:417–420.
    429.
    Hocquet D, Berthelot P, Roussel-Delvallez M, Favre R, Jeannot K, Bajolet O, Marty N, Grattard F, Mariani-Kurkdjian P, Bingen E, Husson MO, Couetdic G, Plésiat P. 2007. Pseudomonas aeruginosa may accumulate drug resistance mechanisms without losing its ability to cause bloodstream infections. Antimicrob Agents Chemother 51:3531–3536.
    430.
    Nakae T, Nakajima A, Ono T, Saito K, Yoneyama H. 1999. Resistance to β-lactam antibiotics in Pseudomonas aeruginosa due to interplay between the MexAB-OprM efflux pump and β-lactamase. Antimicrob Agents Chemother 43:1301–1303.
    431.
    Llanes C, Köhler T, Patry I, Dehecq B, van Delden C, Plésiat P. 2011. Role of the MexEF-OprN efflux system in low-level resistance of Pseudomonas aeruginosa to ciprofloxacin. Antimicrob Agents Chemother 55:5676–5684.
    432.
    Okamoto K, Gotoh N, Nishino T. 2002. Alterations of susceptibility of Pseudomonas aeruginosa by overproduction of multidrug efflux systems, MexAB-OprM, MexCD-OprJ, and MexXY/OprM to carbapenems: substrate specificities of the efflux systems. J Infect Chemother 8:371–373.
    433.
    Köhler T, Michea-Hamzehpour M, Plésiat P, Kahr AL, Pechère JC. 1997. Differential selection of multidrug efflux systems by quinolones in Pseudomonas aeruginosa. Antimicrob Agents Chemother 41:2540–2543.
    434.
    Aires JR, Köhler T, Nikaido H, Plésiat P. 1999. Involvement of an active efflux system in the natural resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob Agents Chemother 43:2624–2628.
    435.
    Mine T, Morita Y, Kataoka A, Mizushima T, Tsuchiya T. 1999. Expression in Escherichia coli of a new multidrug efflux pump, MexXY, from Pseudomonas aeruginosa. Antimicrob Agents Chemother 43:415–417.
    436.
    Westbrock-Wadman S, Sherman DR, Hickey MJ, Coulter SN, Zhu YQ, Warrener P, Nguyen LY, Shawar RM, Folger KR, Stover CK. 1999. Characterization of a Pseudomonas aeruginosa efflux pump contributing to aminoglycoside impermeability. Antimicrob Agents Chemother 43:2975–2983.
    437.
    Murata T, Gotoh N, Nishino T. 2002. Characterization of outer membrane efflux proteins OpmE, OpmD and OpmB of Pseudomonas aeruginosa: molecular cloning and development of specific antisera. FEMS Microbiol Lett 217:57–63.
    438.
    Roy PH, Tetu SG, Larouche A, Elbourne L, Tremblay S, Ren Q, Dodson R, Harkins D, Shay R, Watkins K, Mahamoud Y, Paulsen IT. 2010. Complete genome sequence of the multiresistant taxonomic outlier Pseudomonas aeruginosa PA7. PLoS One 5:e8842.
    439.
    Baum EZ, Crespo-Carbone SM, Morrow BJ, Davies TA, Foleno BD, He W, Queenan AM, Bush K. 2009. Effect of MexXY overexpression on ceftobiprole susceptibility in Pseudomonas aeruginosa. Antimicrob Agents Chemother 53:2785–2790.
    440.
    Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. 2000. Substrate specificities of MexAB-OprM, MexCD-OprJ, and MexXY-OprM efflux pumps in Pseudomonas aeruginosa. Antimicrob Agents Chemother 44:3322–3327.
    441.
    Jeannot K, Sobel ML, El Garch F, Poole K, Plésiat P. 2005. Induction of the MexXY efflux pump in Pseudomonas aeruginosa is dependent on drug-ribosome interaction. J Bacteriol 187:5341–5346.
    442.
    Zhao Q, Li X-Z, Srikumar R, Poole K. 1998. Contribution of outer membrane efflux protein OprM to antibiotic resistance in Pseudomonas aeruginosa independent of MexAB. Antimicrob Agents Chemother 42:1682–1688.
    443.
    Hocquet D, Muller A, Blanc K, Plésiat P, Talon D, Monnet DL, Bertrand X. 2008. Relationship between antibiotic use and incidence of MexXY-OprM overproducers among clinical isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother 52:1173–1175.
    444.
    Muller C, Plésiat P, Jeannot K. 2011. A two-component regulatory system interconnects resistance to polymyxins, aminoglycosides, fluoroquinolones, and β-lactams in Pseudomonas aeruginosa. Antimicrob Agents Chemother 55:1211–1221.
    445.
    Caughlan RE, Sriram S, Daigle DM, Woods AL, Buco J, Peterson RL, Dzink-Fox J, Walker S, Dean CR. 2009. Fmt bypass in Pseudomonas aeruginosa causes induction of MexXY efflux pump expression. Antimicrob Agents Chemother 53:5015–5021.
    446.
    Vogne C, Aires JR, Bailly C, Hocquet D, Plésiat P. 2004. Role of the multidrug efflux system MexXY in the emergence of moderate resistance to aminoglycosides among Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob Agents Chemother 48:1676–1680.
    447.
    Smith EE, Buckley DG, Wu Z, Saenphimmachak C, Hoffman LR, D'Argenio DA, Miller SI, Ramsey BW, Speert DP, Moskowitz SM, Burns JL, Kaul R, Olson MV. 2006. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci U S A 103:8487–8492.
    448.
    Feliziani S, Lujan AM, Moyano AJ, Sola C, Bocco JL, Montanaro P, Canigia LF, Argarana CE, Smania AM. 2010. Mucoidy, quorum sensing, mismatch repair and antibiotic resistance in Pseudomonas aeruginosa from cystic fibrosis chronic airways infections. PLoS One 5:e12669.
    449.
    Mulcahy LR, Burns JL, Lory S, Lewis K. 2010. Emergence of Pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis. J Bacteriol 192:6191–6199.
    450.
    Qin X, Zerr DM, McNutt MA, Berry JE, Burns JL, Kapur RP. 2012. Pseudomonas aeruginosa syntrophy in chronically colonized airways of cystic fibrosis patients. Antimicrob Agents Chemother 56:5971–5981.
    451.
    Llanes C, Pourcel C, Richardot C, Plésiat P, Fichant G, Cavallo JD, Merens A, GERPA Study Group. 2013. Diversity of β-lactam resistance mechanisms in cystic fibrosis isolates of Pseudomonas aeruginosa: a French multicentre study. J Antimicrob Chemother 68:1763–1771.
    452.
    Guénard S, Muller C, Monlezun L, Benas P, Broutin I, Jeannot K, Plésiat P. 2014. Multiple mutations lead to MexXY-OprM-dependent aminoglycoside resistance in clinical strains of Pseudomonas aeruginosa. Antimicrob Agents Chemother 58:221–228.
    453.
    Galli F, Battistoni A, Gambari R, Pompella A, Bragonzi A, Pilolli F, Iuliano L, Piroddi M, Dechecchi MC, Cabrini G, Working Group on Inflammation in Cystic Fibrosis. 2012. Oxidative stress and antioxidant therapy in cystic fibrosis. Biochim Biophys Acta 1822:690–713.
    454.
    Fraud S, Poole K. 2011. Oxidative stress induction of the MexXY multidrug efflux genes and promotion of aminoglycoside resistance development in Pseudomonas aeruginosa. Antimicrob Agents Chemother 55:1068–1074.
    455.
    Hocquet D, Nordmann P, El Garch F, Cabanne L, Plésiat P. 2006. Involvement of the MexXY-OprM efflux system in emergence of cefepime resistance in clinical strains of Pseudomonas aeruginosa. Antimicrob Agents Chemother 50:1347–1351.
    456.
    Peña C, Suarez C, Tubau F, Juan C, Moya B, Dominguez MA, Oliver A, Pujol M, Ariza J. 2009. Nosocomial outbreak of a non-cefepime-susceptible ceftazidime-susceptible Pseudomonas aeruginosa strain overexpressing MexXY-OprM and producing an integron-borne PSE-1 β-lactamase. J Clin Microbiol 47:2381–2387.
    457.
    Morita Y, Tomida J, Kawamura Y. 2012. Primary mechanisms mediating aminoglycoside resistance in the multidrug-resistant Pseudomonas aeruginosa clinical isolate PA7. Microbiology 158:1071–1083.
    458.
    Alguel Y, Lu D, Quade N, Sauter S, Zhang X. 2010. Crystal structure of MexZ, a key repressor responsible for antibiotic resistance in Pseudomonas aeruginosa. J Struct Biol 172:305–310.
    459.
    Jahandideh S. 2013. Diversity in structural consequences of MexZ mutations in Pseudomonas aeruginosa. Chem Biol Drug Des 81:600–606.
    460.
    El'Garch F, Jeannot K, Hocquet D, Llanes-Barakat C, Plésiat P. 2007. Cumulative effects of several nonenzymatic mechanisms on the resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob Agents Chemother 51:1016–1021.
    461.
    Lau CH, Fraud S, Jones M, Peterson SN, Poole K. 2012. Reduced expression of the rplU-rpmA ribosomal protein operon in mexXY-expressing pan-aminoglycoside-resistant mutants of Pseudomonas aeruginosa. Antimicrob Agents Chemother 56:5171–5179.
    462.
    Martha B, Croisier D, Durand D, Hocquet D, Plésiat P, Piroth L, Portier H, Chavanet P. 2006. In-vivo impact of the MexXY efflux system on aminoglycoside efficacy in an experimental model of Pseudomonas aeruginosa pneumonia treated with tobramycin. Clin Microbiol Infect 12:426–432.
    463.
    Pumbwe L, Glass D, Wexler HM. 2006. Efflux pump overexpression in multiple-antibiotic-resistant mutants of Bacteroides fragilis. Antimicrob Agents Chemother 50:3150–3153.
    464.
    Bruchmann S, Dotsch A, Nouri B, Chaberny IF, Haussler S. 2013. Quantitative contributions of target alteration and decreased drug accumulation to Pseudomonas aeruginosa fluoroquinolone resistance. Antimicrob Agents Chemother 57:1361–1368.
    465.
    Poole K, Gotoh N, Tsujimoto H, Zhao Q, Wada A, Yamasaki T, Neshat S, Yamagishi J, Li X-Z, Nishino T. 1996. Overexpression of the mexC-mexD-oprJ efflux operon in nfxB-type multidrug-resistant strains of Pseudomonas aeruginosa. Mol Microbiol 21:713–724.
    466.
    Morita Y, Murata T, Mima T, Shiota S, Kuroda T, Mizushima T, Gotoh N, Nishino T, Tsuchiya T. 2003. Induction of mexCD-oprJ operon for a multidrug efflux pump by disinfectants in wild-type Pseudomonas aeruginosa PAO1. J Antimicrob Chemother 51:991–994.
    467.
    Fraud S, Campigotto AJ, Chen Z, Poole K. 2008. MexCD-OprJ multidrug efflux system of Pseudomonas aeruginosa: involvement in chlorhexidine resistance and induction by membrane-damaging agents dependent upon the AlgU stress response sigma factor. Antimicrob Agents Chemother 52:4478–4482.
    468.
    Masuda N, Gotoh N, Ohya S, Nishino T. 1996. Quantitative correlation between susceptibility and OprJ production in NfxB mutants of Pseudomonas aeruginosa. Antimicrob Agents Chemother 40:909–913.
    469.
    Gotoh N, Tsujimoto H, Tsuda M, Okamoto K, Nomura A, Wada T, Nakahashi M, Nishino T. 1998. Characterization of the MexC-MexD-OprJ multidrug efflux system in ΔmexA-mexB-oprM mutants of Pseudomonas aeruginosa. Antimicrob Agents Chemother 42:1938–1943.
    470.
    Masuda N, Sakagawa E, Ohya S, Gotoh N, Nishino T. 2001. Hypersusceptibility of the Pseudomonas aeruginosa nfxB mutant to β-lactams due to reduced expression of the AmpC β-lactamase. Antimicrob Agents Chemother 45:1284–1286.
    471.
    Wolter DJ, Hanson ND, Lister PD. 2005. AmpC and OprD are not involved in the mechanism of imipenem hypersusceptibility among Pseudomonas aeruginosa isolates overexpressing the MexCD-OprJ efflux pump. Antimicrob Agents Chemother 49:4763–4766.
    472.
    Mulet X, Moya B, Juan C, Macia MD, Pérez JL, Blazquez J, Oliver A. 2011. Antagonistic interactions of Pseudomonas aeruginosa antibiotic resistance mechanisms in planktonic but not biofilm growth. Antimicrob Agents Chemother 55:4560–4568.
    473.
    Giwercman B, Meyer C, Lambert PA, Reinert C, Hoiby N. 1992. High-level β-lactamase activity in sputum samples from cystic fibrosis patients during antipseudomonal treatment. Antimicrob Agents Chemother 36:71–76.
    474.
    Jeannot K, Elsen S, Köhler T, Attree I, van Delden C, Plésiat P. 2008. Resistance and virulence of Pseudomonas aeruginosa clinical strains overproducing the MexCD-OprJ efflux pump. Antimicrob Agents Chemother 52:2455–2462.
    475.
    Reinhardt A, Köhler T, Wood P, Rohner P, Dumas JL, Ricou B, van Delden C. 2007. Development and persistence of antimicrobial resistance in Pseudomonas aeruginosa: a longitudinal observation in mechanically ventilated patients. Antimicrob Agents Chemother 51:1341–1350.
    476.
    Rodríguez-Martínez JM, Poirel L, Nordmann P. 2009. Molecular epidemiology and mechanisms of carbapenem resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 53:4783–4788.
    477.
    Chiang WC, Pamp SJ, Nilsson M, Givskov M, Tolker-Nielsen T. 2012. The metabolically active subpopulation in Pseudomonas aeruginosa biofilms survives exposure to membrane-targeting antimicrobials via distinct molecular mechanisms. FEMS Immunol Med Microbiol 65:245–256.
    478.
    Wolter DJ, Black JA, Lister PD, Hanson ND. 2009. Multiple genotypic changes in hypersusceptible strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients do not always correlate with the phenotype. J Antimicrob Chemother 64:294–300.
    479.
    Stickland HG, Davenport PW, Lilley KS, Griffin JL, Welch M. 2010. Mutation of nfxB causes global changes in the physiology and metabolism of Pseudomonas aeruginosa. J Proteome Res 9:2957–2967.
    480.
    Fukuda H, Hosaka M, Hirai K, Iyobe S. 1990. New norfloxacin resistance gene in Pseudomonas aeruginosa PAO. Antimicrob Agents Chemother 34:1757–1761.
    481.
    Rådberg G, Nilsson LE, Svensson S. 1990. Development of quinolone-imipenem cross resistance in Pseudomonas aeruginosa during exposure to ciprofloxacin. Antimicrob Agents Chemother 34:2142–2147.
    482.
    Aubert G, Pozzetto B, Dorche G. 1992. Emergence of quinolone-imipenem cross-resistance in Pseudomonas aeruginosa after fluoroquinolone therapy. J Antimicrob Chemother 29:307–312.
    483.
    Köhler T, Michea-Hamzehpour M, Henze U, Gotoh N, Curty LK, Pechère JC. 1997. Characterization of MexE-MexF-OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa. Mol Microbiol 23:345–354.
    484.
    Maseda H, Yoneyama H, Nakae T. 2000. Assignment of the substrate-selective subunits of the MexEF-OprN multidrug efflux pump of Pseudomonas aeruginosa. Antimicrob Agents Chemother 44:658–664.
    485.
    Fukuda H, Hosaka M, Iyobe S, Gotoh N, Nishino T, Hirai K. 1995. nfxC-type quinolone resistance in a clinical isolate of Pseudomonas aeruginosa. Antimicrob Agents Chemother 39:790–792.
    486.
    Henrichfreise B, Wiegand I, Luhmer-Becker I, Wiedemann B. 2007. Development of resistance in wild-type and hypermutable Pseudomonas aeruginosa strains exposed to clinical pharmacokinetic profiles of meropenem and ceftazidime simulated in vitro. Antimicrob Agents Chemother 51:3642–3649.
    487.
    Mima T, Sekiya H, Mizushima T, Kuroda T, Tsuchiya T. 2005. Gene cloning and properties of the RND-type multidrug efflux pumps MexPQ-OpmE and MexMN-OprM from Pseudomonas aeruginosa. Microbiol Immunol 49:999–1002.
    488.
    Li Y, Mima T, Komori Y, Morita Y, Kuroda T, Mizushima T, Tsuchiya T. 2003. A new member of the tripartite multidrug efflux pumps, MexVW-OprM, in Pseudomonas aeruginosa. J Antimicrob Chemother 52:572–575.
    489.
    Mima T, Kohira N, Li Y, Sekiya H, Ogawa W, Kuroda T, Tsuchiya T. 2009. Gene cloning and characteristics of the RND-type multidrug efflux pump MuxABC-OpmB possessing two RND components in Pseudomonas aeruginosa. Microbiology 155:3509–3517.
    490.
    Yang L, Chen L, Shen L, Surette M, Duan K. 2011. Inactivation of MuxABC-OpmB transporter system in Pseudomonas aeruginosa leads to increased ampicillin and carbenicillin resistance and decreased virulence. J Microbiol 49:107–114.
    491.
    Mima T, Joshi S, Gomez-Escalada M, Schweizer HP. 2007. Identification and characterization of TriABC-OpmH, a triclosan efflux pump of Pseudomonas aeruginosa requiring two membrane fusion proteins. J Bacteriol 189:7600–7609.
    492.
    Hassan MT, van der Lelie D, Springael D, Romling U, Ahmed N, Mergeay M. 1999. Identification of a gene cluster, czr, involved in cadmium and zinc resistance in Pseudomonas aeruginosa. Gene 238:417–425.
    493.
    Perron K, Caille O, Rossier C, Van Delden C, Dumas JL, Köhler T. 2004. CzcR-CzcS, a two-component system involved in heavy metal and carbapenem resistance in Pseudomonas aeruginosa. J Biol Chem 279:8761–8768.
    494.
    Dijkshoorn L, Nemec A, Seifert H. 2007. An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat Rev Microbiol 5:939–951.
    495.
    Garcia-Quintanilla M, Pulido MR, Lopez-Rojas R, Pachon J, McConnell MJ. 2013. Emerging therapies for multidrug resistant Acinetobacter baumannii. Trends Microbiol 21:157–163.
    496.
    Fournier PE, Vallenet D, Barbe V, Audic S, Ogata H, Poirel L, Richet H, Robert C, Mangenot S, Abergel C, Nordmann P, Weissenbach J, Raoult D, Claverie JM. 2006. Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genet 2:e7.
    497.
    Adams MD, Goglin K, Molyneaux N, Hujer KM, Lavender H, Jamison JJ, MacDonald IJ, Martin KM, Russo T, Campagnari AA, Hujer AM, Bonomo RA, Gill SR. 2008. Comparative genome sequence analysis of multidrug-resistant Acinetobacter baumannii. J Bacteriol 190:8053–8064.
    498.
    Krizova L, Dijkshoorn L, Nemec A. 2011. Diversity and evolution of AbaR genomic resistance islands in Acinetobacter baumannii strains of European clone I. Antimicrob Agents Chemother 55:3201–3206.
    499.
    Zhou H, Zhang T, Yu D, Pi B, Yang Q, Zhou J, Hu S, Yu Y. 2011. Genomic analysis of the multidrug-resistant Acinetobacter baumannii strain MDR-ZJ06 widely spread in China. Antimicrob Agents Chemother 55:4506–4512.
    500.
    Zhu L, Yan Z, Zhang Z, Zhou Q, Zhou J, Wakeland EK, Fang X, Xuan Z, Shen D, Li QZ. 2013. Complete genome analysis of three Acinetobacter baumannii clinical isolates in China for insight into the diversification of drug resistance elements. PLoS One 8:e66584.
    501.
    Bratu S, Landman D, George A, Salvani J, Quale J. 2009. Correlation of the expression of acrB and the regulatory genes marA, soxS and ramA with antimicrobial resistance in clinical isolates of Klebsiella pneumoniae endemic to New York City. J Antimicrob Chemother 64:278–283.
    502.
    Rumbo C, Gato E, Lopez M, Ruiz de Alegria C, Fernández-Cuenca F, Martínez-Martínez L, Vila J, Pachon J, Cisneros JM, Rodríguez-Bano J, Pascual A, Bou G, Tomás M, Spanish Group of Nosocomial Infections and Mechanisms of Action and Resistance to Antimicrobials, Spanish Society of Clinical Microbiology and Infectious Diseases, Spanish Network for Research in Infectious Diseases. 2013. Contribution of efflux pumps, porins, and β-lactamases to multidrug resistance in clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother 57:5247–5257.
    503.
    Figueiredo S, Poirel L, Croize J, Recule C, Nordmann P. 2009. In vivo selection of reduced susceptibility to carbapenems in Acinetobacter baumannii related to ISAba1-mediated overexpression of the natural blaOXA-66 oxacillinase gene. Antimicrob Agents Chemother 53:2657–2659.
    504.
    Higgins PG, Schneiders T, Hamprecht A, Seifert H. 2010. In vivo selection of a missense mutation in adeR and conversion of the novel blaOXA-164 gene into blaOXA-58 in carbapenem-resistant Acinetobacter baumannii isolates from a hospitalized patient. Antimicrob Agents Chemother 54:5021–5027.
    505.
    Hua X, Zhou H, Jiang Y, Feng Y, Chen Q, Ruan Z, Yu Y. 2012. Genome sequences of two multidrug-resistant Acinetobacter baumannii strains isolated from a patient before and after treatment with tigecycline. J Bacteriol 194:6979–6980.
    506.
    Asai S, Umezawa K, Iwashita H, Ohshima T, Ohashi M, Sasaki M, Hayashi H, Matsui M, Shibayama K, Inokuchi S, Miyachi H. 2014. An outbreak of blaOXA-51-like- and blaOXA-66-positive Acinetobacter baumannii ST208 in the emergency intensive care unit. J Med Microbiol 63:1517–1523.
    507.
    Sato K, Nakae T. 1991. Outer membrane permeability of Acinetobacter calcoaceticus and its implication in antibiotic resistance. J Antimicrob Chemother 28:35–45.
    508.
    Jyothisri K, Deepak V, Rajeswari MR. 1999. Purification and characterization of a major 40 kDa outer membrane protein of Acinetobacter baumannii. FEBS Lett 443:57–60.
    509.
    Smani Y, Fabrega A, Roca I, Sánchez-Encinales V, Vila J, Pachon J. 2014. Role of OmpA in the multidrug resistance phenotype of Acinetobacter baumannii. Antimicrob Agents Chemother 58:1806–1808.
    510.
    Chusri S, Na-Phatthalung P, Siriyong T, Paosen S, Voravuthikunchai SP. 2014. Holarrhena antidysenterica as a resistance modifying agent against Acinetobacter baumannii: its effects on bacterial outer membrane permeability and efflux pumps. Microbiol Res 169:417–424.
    511.
    Lorenzi V, Muselli A, Bernardini AF, Berti L, Pagès JM, Amaral L, Bolla JM. 2009. Geraniol restores antibiotic activities against multidrug-resistant isolates from Gram-negative species. Antimicrob Agents Chemother 53:2209–2211.
    512.
    Wang HM, Chen CY, Chen HA, Huang WC, Lin WR, Chen TC, Lin CY, Chien HJ, Lu PL, Lin CM, Chen YH. 2010. Zingiber officinale (ginger) compounds have tetracycline-resistance modifying effects against clinical extensively drug-resistant Acinetobacter baumannii. Phytother Res 24:1825–1830.
    513.
    Limansky AS, Mussi MA, Viale AM. 2002. Loss of a 29-kilodalton outer membrane protein in Acinetobacter baumannii is associated with imipenem resistance. J Clin Microbiol 40:4776–4778.
    514.
    Mussi MA, Limansky AS, Viale AM. 2005. Acquisition of resistance to carbapenems in multidrug-resistant clinical strains of Acinetobacter baumannii: natural insertional inactivation of a gene encoding a member of a novel family of b-barrel outer membrane proteins. Antimicrob Agents Chemother 49:1432–1440.
    515.
    Siroy A, Molle V, Lemaitre-Guillier C, Vallenet D, Pestel-Caron M, Cozzone AJ, Jouenne T, De E. 2005. Channel formation by CarO, the carbapenem resistance-associated outer membrane protein of Acinetobacter baumannii. Antimicrob Agents Chemother 49:4876–4883.
    516.
    Catel-Ferreira M, Coadou G, Molle V, Mugnier P, Nordmann P, Siroy A, Jouenne T, De E. 2011. Structure-function relationships of CarO, the carbapenem resistance-associated outer membrane protein of Acinetobacter baumannii. J Antimicrob Chemother 66:2053–2056.
    517.
    Mussi MA, Relling VM, Limansky AS, Viale AM. 2007. CarO, an Acinetobacter baumannii outer membrane protein involved in carbapenem resistance, is essential for L-ornithine uptake. FEBS Lett 581:5573–5578.
    518.
    Lee Y, Kim CK, Lee H, Jeong SH, Yong D, Lee K. 2011. A novel insertion sequence, ISAba10, inserted into ISAba1 adjacent to the blaOXA-23 gene and disrupting the outer membrane protein gene carO in Acinetobacter baumannii. Antimicrob Agents Chemother 55:361–363.
    519.
    Mussi MA, Limansky AS, Relling V, Ravasi P, Arakaki A, Actis LA, Viale AM. 2011. Horizontal gene transfer and assortative recombination within the Acinetobacter baumannii clinical population provide genetic diversity at the single carO gene, encoding a major outer membrane protein channel. J Bacteriol 193:4736–4748.
    520.
    Clark RB. 1996. Imipenem resistance among Acinetobacter baumannii: association with reduced expression of a 33-36 kDa outer membrane protein. J Antimicrob Chemother 38:245–251.
    521.
    Bou G, Cervero G, Dominguez MA, Quereda C, Martínez-Beltran J. 2000. Characterization of a nosocomial outbreak caused by a multiresistant Acinetobacter baumannii strain with a carbapenem-hydrolyzing enzyme: high-level carbapenem resistance in A. baumannii is not due solely to the presence of β-lactamases. J Clin Microbiol 38:3299–3305.
    522.
    del Mar Tomás M, Beceiro A, Pérez A, Velasco D, Moure R, Villanueva R, Martínez-Beltran J, Bou G. 2005. Cloning and functional analysis of the gene encoding the 33- to 36-kilodalton outer membrane protein associated with carbapenem resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 49:5172–5175.
    523.
    Hood MI, Jacobs AC, Sayood K, Dunman PM, Skaar EP. 2010. Acinetobacter baumannii increases tolerance to antibiotics in response to monovalent cations. Antimicrob Agents Chemother 54:1029–1041.
    524.
    Magnet S, Courvalin P, Lambert T. 2001. Resistance-nodulation-cell division-type efflux pump involved in aminoglycoside resistance in Acinetobacter baumannii strain BM4454. Antimicrob Agents Chemother 45:3375–3380.
    525.
    Nemec A, Maixnerova M, van der Reijden TJ, van den Broek PJ, Dijkshoorn L. 2007. Relationship between the AdeABC efflux system gene content, netilmicin susceptibility and multidrug resistance in a genotypically diverse collection of Acinetobacter baumannii strains. J Antimicrob Chemother 60:483–489.
    526.
    Ruzin A, Keeney D, Bradford PA. 2007. AdeABC multidrug efflux pump is associated with decreased susceptibility to tigecycline in Acinetobacter calcoaceticus-Acinetobacter baumannii complex. J Antimicrob Chemother 59:1001–1004.
    527.
    Valentine SC, Contreras D, Tan S, Real LJ, Chu S, Xu HH. 2008. Phenotypic and molecular characterization of Acinetobacter baumannii clinical isolates from nosocomial outbreaks in Los Angeles County, California. J Clin Microbiol 46:2499–2507.
    528.
    Lin L, Ling BD, Li X-Z. 2009. Distribution of the multidrug efflux pump genes, adeABC, adeDE and adeIJK, and class 1 integron genes in multiple-antimicrobial-resistant clinical isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus complex. Int J Antimicrob Agents 33:27–32.
    529.
    Landman D, Butnariu M, Bratu S, Quale J. 2009. Genetic relatedness of multidrug-resistant Acinetobacter baumannii endemic to New York City. Epidemiol Infect 137:174–180.
    530.
    Rajamohan G, Srinivasan VB, Gebreyes WA. 2010. Novel role of Acinetobacter baumannii RND efflux transporters in mediating decreased susceptibility to biocides. J Antimicrob Chemother 65:228–232.
    531.
    Hornsey M, Ellington MJ, Doumith M, Thomas CP, Gordon NC, Wareham DW, Quinn J, Lolans K, Livermore DM, Woodford N. 2010. AdeABC-mediated efflux and tigecycline MICs for epidemic clones of Acinetobacter baumannii. J Antimicrob Chemother 65:1589–1593.
    532.
    Fernando D, Zhanel G, Kumar A. 2013. Antibiotic resistance and expression of resistance-nodulation-division pump- and outer membrane porin-encoding genes in Acinetobacter species isolated from Canadian hospitals. Can J Infect Dis Med Microbiol 24:17–21.
    533.
    Deng M, Zhu MH, Li JJ, Bi S, Sheng ZK, Hu FS, Zhang JJ, Chen W, Xue XW, Sheng JF, Li LJ. 2014. Molecular epidemiology and mechanisms of tigecycline resistance in clinical isolates of Acinetobacter baumannii from a Chinese university hospital. Antimicrob Agents Chemother 58:297–303.
    534.
    Lee SY, Yun SH, Lee YG, Choi CW, Leem SH, Park EC, Kim GH, Lee JC, Kim SI. 2014. Proteogenomic characterization of antimicrobial resistance in extensively drug-resistant Acinetobacter baumannii DU202. J Antimicrob Chemother 69:1483–1491.
    535.
    Peleg AY, Potoski BA, Rea R, Adams J, Sethi J, Capitano B, Husain S, Kwak EJ, Bhat SV, Paterson DL. 2007. Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report. J Antimicrob Chemother 59:128–131.
    536.
    Peleg AY, Adams J, Paterson DL. 2007. Tigecycline efflux as a mechanism for nonsusceptibility in Acinetobacter baumannii. Antimicrob Agents Chemother 51:2065–2069.
    537.
    Bratu S, Landman D, Martin DA, Georgescu C, Quale J. 2008. Correlation of antimicrobial resistance with β-lactamases, the OmpA-like porin, and efflux pumps in clinical isolates of Acinetobacter baumannii endemic to New York City. Antimicrob Agents Chemother 52:2999–3005.
    538.
    Sun JR, Perng CL, Chan MC, Morita Y, Lin JC, Su CM, Wang WY, Chang TY, Chiueh TS. 2012. A truncated AdeS kinase protein generated by ISAba1 insertion correlates with tigecycline resistance in Acinetobacter baumannii. PLoS One 7:e49534.
    539.
    Fluit AC, Florijn A, Verhoef J, Milatovic D. 2005. Presence of tetracycline resistance determinants and susceptibility to tigecycline and minocycline. Antimicrob Agents Chemother 49:1636–1638.
    540.
    Horiyama T, Nikaido E, Yamaguchi A, Nishino K. 2011. Roles of Salmonella multidrug efflux pumps in tigecycline resistance. J Antimicrob Chemother 66:105–110.
    541.
    Chen Q, Li X, Zhou H, Jiang Y, Chen Y, Hua X, Yu Y. 2014. Decreased susceptibility to tigecycline in Acinetobacter baumannii mediated by a mutation in trm encoding SAM-dependent methyltransferase. J Antimicrob Chemother 69:72–76.
    542.
    Damier-Piolle L, Magnet S, Bremont S, Lambert T, Courvalin P. 2008. AdeIJK, a resistance-nodulation-cell division pump effluxing multiple antibiotics in Acinetobacter baumannii. Antimicrob Agents Chemother 52:557–562.
    543.
    Rosenfeld N, Bouchier C, Courvalin P, Perichon B. 2012. Expression of the resistance-nodulation-cell division pump AdeIJK in Acinetobacter baumannii is regulated by AdeN, a TetR-type regulator. Antimicrob Agents Chemother 56:2504–2510.
    544.
    Fernando DM, Xu W, Loewen PC, Zhanel GG, Kumar A. 2014. Triclosan can select for an AdeIJK overexpressing mutant of Acinetobacter baumannii ATCC 17978 that displays reduced susceptibility to multiple antibiotics. Antimicrob Agents Chemother 58:6424–6431.
    545.
    Sugawara E, Nikaido H. 2014. Properties of AdeABC and AdeIJK efflux systems of Acinetobacter baumannii compared with those of the AcrAB-TolC system of Escherichia coli. Antimicrob Agents Chemother 58:7250–7257.
    546.
    Coyne S, Guigon G, Courvalin P, Perichon B. 2010. Screening and quantification of the expression of antibiotic resistance genes in Acinetobacter baumannii with a microarray. Antimicrob Agents Chemother 54:333–340.
    547.
    Coyne S, Rosenfeld N, Lambert T, Courvalin P, Perichon B. 2010. Overexpression of resistance-nodulation-cell division pump AdeFGH confers multidrug resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 54:4389–4393.
    548.
    Lin MF, Lin YY, Yeh HW, Lan CY. 2014. Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility. BMC Microbiol 14:119.
    549.
    Roca I, Espinal P, Marti S, Vila J. 2011. First identification and characterization of an AdeABC-like efflux pump in Acinetobacter genomospecies 13TU. Antimicrob Agents Chemother 55:1285–1286.
    550.
    Pannek S, Higgins PG, Steinke P, Jonas D, Akova M, Bohnert JA, Seifert H, Kern WV. 2006. Multidrug efflux inhibition in Acinetobacter baumannii: comparison between 1-(1-naphthylmethyl)-piperazine and phenyl-arginine-β-naphthylamide. J Antimicrob Chemother 57:970–974.
    551.
    Bean DC, Wareham DW. 2009. Paradoxical effect of 1-(1-naphthylmethyl)-piperazine on resistance to tetracyclines in multidrug-resistant Acinetobacter baumannii. J Antimicrob Chemother 63:349–352.
    552.
    Cortez-Cordova J, Kumar A. 2011. Activity of the efflux pump inhibitor phenylalanine-arginine β-naphthylamide against the AdeFGH pump of Acinetobacter baumannii. Int J Antimicrob Agents 37:420–424.
    553.
    Ribera A, Ruiz J, Jiminez de Anta MT, Vila J. 2002. Effect of an efflux pump inhibitor on the MIC of nalidixic acid for Acinetobacter baumannii and Stenotrophomonas maltophilia clinical isolates. J Antimicrob Chemother 49:697–698.
    554.
    Golanbar GD, Lam CK, Chu YM, Cueva C, Tan SW, Silva I, Xu HH. 2011. Phenotypic and molecular characterization of Acinetobacter clinical isolates obtained from inmates of California correctional facilities. J Clin Microbiol 49:2121–2131.
    555.
    Giannouli M, Di Popolo A, Durante-Mangoni E, Bernardo M, Cuccurullo S, Amato G, Tripodi MF, Triassi M, Utili R, Zarrilli R. 2012. Molecular epidemiology and mechanisms of rifampicin resistance in Acinetobacter baumannii isolates from Italy. Int J Antimicrob Agents 39:58–63.
    556.
    Yang Y, Chua KL. 2013. Assessment of the effect of efflux pump inhibitors on in vitro antimicrobial susceptibility of multidrug-resistant Acinetobacter baumannii. Int J Antimicrob Agents 42:283–284.
    557.
    Ni W, Cai X, Liang B, Cai Y, Cui J, Wang R. 2014. Effect of proton pump inhibitors on in vitro activity of tigecycline against several common clinical pathogens. PLoS One 9:e86715.
    558.
    Rajamohan G, Srinivasan VB, Gebreyes WA. 2010. Molecular and functional characterization of a novel efflux pump, AmvA, mediating antimicrobial and disinfectant resistance in Acinetobacter baumannii. J Antimicrob Chemother 65:1919–1925.
    559.
    Hou PF, Chen XY, Yan GF, Wang YP, Ying CM. 2012. Study of the correlation of imipenem resistance with efflux pumps AdeABC, AdeIJK, AdeDE and AbeM in clinical isolates of Acinetobacter baumannii. Chemotherapy 58:152–158.
    560.
    Eijkelkamp BA, Hassan KA, Paulsen IT, Brown MH. 2011. Development of a high-throughput cloning strategy for characterization of Acinetobacter baumannii drug transporter proteins. J Mol Microbiol Biotechnol 20:211–219.
    561.
    Roca I, Marti S, Espinal P, Martínez P, Gibert I, Vila J. 2009. CraA, a major facilitator superfamily efflux pump associated with chloramphenicol resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 53:4013–4014.
    562.
    Vilacoba E, Almuzara M, Gulone L, Traglia GM, Figueroa SA, Sly G, Fernández A, Centron D, Ramirez MS. 2013. Emergence and spread of plasmid-borne tet(B)::ISCR2 in minocycline-resistant Acinetobacter baumannii isolates. Antimicrob Agents Chemother 57:651–654.
    563.
    Hassan KA, Jackson SM, Penesyan A, Patching SG, Tetu SG, Eijkelkamp BA, Brown MH, Henderson PJ, Paulsen IT. 2013. Transcriptomic and biochemical analyses identify a family of chlorhexidine efflux proteins. Proc Natl Acad Sci U S A 110:20254–20259.
    564.
    Fuangthong M, Julotok M, Chintana W, Kuhn K, Rittiroongrad S, Vattanaviboon P, Mongkolsuk S. 2011. Exposure of Acinetobacter baylyi ADP1 to the biocide chlorhexidine leads to acquired resistance to the biocide itself and to oxidants. J Antimicrob Chemother 66:319–322.
    565.
    Zhang L, Li XZ, Poole K. 2000. Multiple antibiotic resistance in Stenotrophomonas maltophilia: involvement of a multidrug efflux system. Antimicrob Agents Chemother 44:287–293.
    566.
    Brooke JS. 2012. Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev 25:2–41.
    567.
    Mett H, Rosta S, Schacher B, Frei R. 1988. Outer membrane permeability and β-lactamase content in Pseudomonas maltophilia clinical isolates and laboratory mutants. Rev Infect Dis 10:765–769.
    568.
    McKay GA, Woods DE, MacDonald KL, Poole K. 2003. Role of phosphoglucomutase of Stenotrophomonas maltophilia in lipopolysaccharide biosynthesis, virulence, and antibiotic resistance. Infect Immun 71:3068–3075.
    569.
    Alonso A, Martínez JL. 1997. Multiple antibiotic resistance in Stenotrophomonas maltophilia. Antimicrob Agents Chemother 41:1140–1142.
    570.
    Crossman LC, Gould VC, Dow JM, Vernikos GS, Okazaki A, Sebaihia M, Saunders D, Arrowsmith C, Carver T, Peters N, Adlem E, Kerhornou A, Lord A, Murphy L, Seeger K, Squares R, Rutter S, Quail MA, Rajandream MA, Harris D, Churcher C, Bentley SD, Parkhill J, Thomson NR, Avison MB. 2008. The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants. Genome Biol 9:R74.
    571.
    Li X-Z, Zhang L, Poole K. 2002. SmeC, an outer membrane multidrug efflux protein of Stenotrophomonas maltophilia. Antimicrob Agents Chemother 46:333–343.
    572.
    Chang LL, Chen HF, Chang CY, Lee TM, Wu WJ. 2004. Contribution of integrons, and SmeABC and SmeDEF efflux pumps to multidrug resistance in clinical isolates of Stenotrophomonas maltophilia. J Antimicrob Chemother 53:518–521.
    573.
    Cho HH, Sung JY, Kwon KC, Koo SH. 2012. Expression of Sme efflux pumps and multilocus sequence typing in clinical isolates of Stenotrophomonas maltophilia. Ann Lab Med 32:38–43.
    574.
    Zhang L, Li XZ, Poole K. 2001. SmeDEF multidrug efflux pump contributes to intrinsic multidrug resistance in Stenotrophomonas maltophilia. Antimicrob Agents Chemother 45:3497–3503.
    575.
    Alonso A, Martínez JL. 2001. Expression of multidrug efflux pump SmeDEF by clinical isolates of Stenotrophomonas maltophilia. Antimicrob Agents Chemother 45:1879–1881.
    576.
    Gould VC, Avison MB. 2006. SmeDEF-mediated antimicrobial drug resistance in Stenotrophomonas maltophilia clinical isolates having defined phylogenetic relationships. J Antimicrob Chemother 57:1070–1076.
    577.
    Sánchez P, Moreno E, Martínez JL. 2005. The biocide triclosan selects Stenotrophomonas maltophilia mutants that overproduce the SmeDEF multidrug efflux pump. Antimicrob Agents Chemother 49:781–782.
    578.
    García-León G, Salgado F, Oliveros JC, Sánchez MB, Martínez JL. 2014. Interplay between intrinsic and acquired resistance to quinolones in Stenotrophomonas maltophilia. Environ Microbiol 16:1282–1296.
    579.
    Lin CW, Huang YW, Hu RM, Yang TC. 2014. SmeOP-TolCsm efflux pump contributes to the multidrug resistance of Stenotrophomonas maltophilia. Antimicrob Agents Chemother 58:2405–2408.
    580.
    Huang YW, Hu RM, Yang TC. 2013. Role of the pcm-tolCsm operon in the multidrug resistance of Stenotrophomonas maltophilia. J Antimicrob Chemother 68:1987–1993.
    581.
    Chen CH, Huang CC, Chung TC, Hu RM, Huang YW, Yang TC. 2011. Contribution of resistance-nodulation-division efflux pump operon smeU1-V-W-U2-X to multidrug resistance of Stenotrophomonas maltophilia. Antimicrob Agents Chemother 55:5826–5833.
    582.
    Huang YW, Liou RS, Lin YT, Huang HH, Yang TC. 2014. A linkage between SmeIJK efflux pump, cell envelope integrity, and σE-mediated envelope stress response in Stenotrophomonas maltophilia. PLoS One 9:e111784.
    583.
    Hu RM, Liao ST, Huang CC, Huang YW, Yang TC. 2012. An inducible fusaric acid tripartite efflux pump contributes to the fusaric acid resistance in Stenotrophomonas maltophilia. PLoS One 7:e51053.
    584.
    Lin YT, Huang YW, Liou RS, Chang YC, Yang TC. 2014. MacABCsm, an ABC-type tripartite efflux pump of Stenotrophomonas maltophilia involved in drug resistance, oxidative and envelope stress tolerances and biofilm formation. J Antimicrob Chemother 69:3221–3226.
    585.
    Al-Hamad A, Upton M, Burnie J. 2009. Molecular cloning and characterization of SmrA, a novel ABC multidrug efflux pump from Stenotrophomonas maltophilia. J Antimicrob Chemother 64:731–734.
    586.
    Al-Hamad A, Burnie J, Upton M. 2011. Enhancement of antibiotic susceptibility of Stenotrophomonas maltophilia using a polyclonal antibody developed against an ABC multidrug efflux pump. Can J Microbiol 57:820–828.
    587.
    Huang YW, Hu RM, Chu FY, Lin HR, Yang TC. 2013. Characterization of a major facilitator superfamily (MFS) tripartite efflux pump EmrCABsm from Stenotrophomonas maltophilia. J Antimicrob Chemother 68:2498–2505.
    588.
    Traxler RM, Lehman MW, Bosserman EA, Guerra MA, Smith TL. 2013. A literature review of laboratory-acquired brucellosis. J Clin Microbiol 51:3055–3062.
    589.
    Paulsen IT, Seshadri R, Nelson KE, Eisen JA, Heidelberg JF, Read TD, Dodson RJ, Umayam L, Brinkac LM, Beanan MJ, Daugherty SC, Deboy RT, Durkin AS, Kolonay JF, Madupu R, Nelson WC, Ayodeji B, Kraul M, Shetty J, Malek J, Van Aken SE, Riedmuller S, Tettelin H, Gill SR, White O, Salzberg SL, Hoover DL, Lindler LE, Halling SM, Boyle SM, Fraser CM. 2002. The Brucella suis genome reveals fundamental similarities between animal and plant pathogens and symbionts. Proc Natl Acad Sci U S A 99:13148–13153.
    590.
    Halling SM, Peterson-Burch BD, Bricker BJ, Zuerner RL, Qing Z, Li LL, Kapur V, Alt DP, Olsen SC. 2005. Completion of the genome sequence of Brucella abortus and comparison to the highly similar genomes of Brucella melitensis and Brucella suis. J Bacteriol 187:2715–2726.
    591.
    Douglas JT, Rosenberg EY, Nikaido H, Verstreate DR, Winter AJ. 1984. Porins of Brucella species. Infect Immun 44:16–21.
    592.
    Roussel G, Matagne A, De Bolle X, Perpete EA, Michaux C. 2012. Purification, refolding and characterization of the trimeric Omp2a outer membrane porin from Brucella melitensis. Protein Expr Purif 83:198–204.
    593.
    Posadas DM, Martin FA, Sabio y Garcia JV, Spera JM, Delpino MV, Baldi P, Campos E, Cravero SL, Zorreguieta A. 2007. The TolC homologue of Brucella suis is involved in resistance to antimicrobial compounds and virulence. Infect Immun 75:379–389.
    594.
    Martin FA, Posadas DM, Carrica MC, Cravero SL, O'Callaghan D, Zorreguieta A. 2009. Interplay between two RND systems mediating antimicrobial resistance in Brucella suis. J Bacteriol 191:2530–2540.
    595.
    Halling SM, Jensen AE. 2006. Intrinsic and selected resistance to antibiotics binding the ribosome: analyses of Brucella 23S rrn, L4, L22, EF-Tu1, EF-Tu2, efflux and phylogenetic implications. BMC Microbiol 6:84.
    596.
    Ravanel N, Gestin B, Maurin M. 2009. In vitro selection of fluoroquinolone resistance in Brucella melitensis. Int J Antimicrob Agents 34:76–81.
    597.
    Valdezate S, Navarro A, Medina-Pascual MJ, Carrasco G, Saez-Nieto JA. 2010. Molecular screening for rifampicin and fluoroquinolone resistance in a clinical population of Brucella melitensis. J Antimicrob Chemother 65:51–53.
    598.
    Biswas S, Rolain JM. 2010. Bartonella infection: treatment and drug resistance. Future Microbiol 5:1719–1731.
    599.
    Biswas S, Raoult D, Rolain JM. 2008. A bioinformatic approach to understanding antibiotic resistance in intracellular bacteria through whole genome analysis. Int J Antimicrob Agents 32:207–220.
    600.
    Li DM, Liu QY, Zhao F, Hu Y, Xiao D, Gu YX, Song XP, Zhang JZ. 2011. Proteomic and bioinformatic analysis of outer membrane proteins of the protobacterium Bartonella henselae (Bartonellaceae). Genet Mol Res 10:1789–1818.
    601.
    Rolain JM, Vayssier-Taussat M, Saisongkorh W, Merhej V, Gimenez G, Robert C, Le Rhun D, Dehio C, Raoult D. 2013. Partial disruption of translational and posttranslational machinery reshapes growth rates of Bartonella birtlesii. mBio 4(2):e00115-13.
    602.
    Rolain JM, Raoult D. 2005. Genome comparison analysis of molecular mechanisms of resistance to antibiotics in the Rickettsia genus. Ann N Y Acad Sci 1063:222–230.
    603.
    Felsheim RF, Kurtti TJ, Munderloh UG. 2009. Genome sequence of the endosymbiont Rickettsia peacockii and comparison with virulent Rickettsia rickettsii: identification of virulence factors. PLoS One 4:e8361.
    604.
    Gillings M, Boucher Y, Labbate M, Holmes A, Krishnan S, Holley M, Stokes HW. 2008. The evolution of class 1 integrons and the rise of antibiotic resistance. J Bacteriol 190:5095–5100.
    605.
    Jakobsen TH, Hansen MA, Jensen PO, Hansen L, Riber L, Cockburn A, Kolpen M, Ronne Hansen C, Ridderberg W, Eickhardt S, Hansen M, Kerpedjiev P, Alhede M, Qvortrup K, Burmolle M, Moser C, Kuhl M, Ciofu O, Givskov M, Sorensen SJ, Hoiby N, Bjarnsholt T. 2013. Complete genome sequence of the cystic fibrosis pathogen Achromobacter xylosoxidans NH44784-1996 complies with important pathogenic phenotypes. PLoS One 8:e68484.
    606.
    Bador J, Amoureux L, Duez JM, Drabowicz A, Siebor E, Llanes C, Neuwirth C. 2011. First description of an RND-type multidrug efflux pump in Achromobacter xylosoxidans, AxyABM. Antimicrob Agents Chemother 55:4912–4914.
    607.
    Bador J, Amoureux L, Blanc E, Neuwirth C. 2013. Innate aminoglycoside resistance of Achromobacter xylosoxidans is due to AxyXY-OprZ, an RND-type multidrug efflux pump. Antimicrob Agents Chemother 57:603–605.
    608.
    Schell MA, Zhao P, Wells L. 2011. Outer membrane proteome of Burkholderia pseudomallei and Burkholderia mallei from diverse growth conditions. J Proteome Res 10:2417–2424.
    609.
    Siritapetawee J, Prinz H, Krittanai C, Suginta W. 2004. Expression and refolding of Omp38 from Burkholderia pseudomallei and Burkholderia thailandensis, and its function as a diffusion porin. Biochem J 384:609–617.
    610.
    Suginta W, Mahendran KR, Chumjan W, Hajjar E, Schulte A, Winterhalter M, Weingart H. 2011. Molecular analysis of antimicrobial agent translocation through the membrane porin BpsOmp38 from an ultraresistant Burkholderia pseudomallei strain. Biochim Biophys Acta 1808:1552–1559.
    611.
    Guglierame P, Pasca MR, De Rossi E, Buroni S, Arrigo P, Manina G, Riccardi G. 2006. Efflux pump genes of the resistance-nodulation-division family in Burkholderia cenocepacia genome. BMC Microbiol 6:66.
    612.
    Perrin E, Fondi M, Papaleo MC, Maida I, Emiliani G, Buroni S, Pasca MR, Riccardi G, Fani R. 2013. A census of RND superfamily proteins in the Burkholderia genus. Future Microbiol 8:923–937.
    613.
    Buroni S, Matthijs N, Spadaro F, Van Acker H, Scoffone VC, Pasca MR, Riccardi G, Coenye T. 2014. Differential roles of RND efflux pumps in antimicrobial drug resistance of sessile and planktonic Burkholderia cenocepacia cells. Antimicrob Agents Chemother 58:7424–7429.
    614.
    Buroni S, Pasca MR, Flannagan RS, Bazzini S, Milano A, Bertani I, Venturi V, Valvano MA, Riccardi G. 2009. Assessment of three resistance-nodulation-cell division drug efflux transporters of Burkholderia cenocepacia in intrinsic antibiotic resistance. BMC Microbiol 9:200.
    615.
    Bazzini S, Udine C, Sass A, Pasca MR, Longo F, Emiliani G, Fondi M, Perrin E, Decorosi F, Viti C, Giovannetti L, Leoni L, Fani R, Riccardi G, Mahenthiralingam E, Buroni S. 2011. Deciphering the role of RND efflux transporters in Burkholderia cenocepacia. PLoS One 6:e18902.
    616.
    Tseng SP, Tsai WC, Liang CY, Lin YS, Huang JW, Chang CY, Tyan YC, Lu PL. 2014. The contribution of antibiotic resistance mechanisms in clinical Burkholderia cepacia complex isolates: an emphasis on efflux pump activity. PLoS One 9:e104986.
    617.
    Chan YY, Tan TM, Ong YM, Chua KL. 2004. BpeAB-OprB, a multidrug efflux pump in Burkholderia pseudomallei. Antimicrob Agents Chemother 48:1128–1135.
    618.
    Rajendran R, Quinn RF, Murray C, McCulloch E, Williams C, Ramage G. 2010. Efflux pumps may play a role in tigecycline resistance in Burkholderia species. Int J Antimicrob Agents 36:151–154.
    619.
    Sass A, Marchbank A, Tullis E, Lipuma JJ, Mahenthiralingam E. 2011. Spontaneous and evolutionary changes in the antibiotic resistance of Burkholderia cenocepacia observed by global gene expression analysis. BMC Genomics 12:373.
    620.
    Kumar A, Mayo M, Trunck LA, Cheng AC, Currie BJ, Schweizer HP. 2008. Expression of resistance-nodulation-cell-division efflux pumps in commonly used Burkholderia pseudomallei strains and clinical isolates from northern Australia. Trans R Soc Trop Med Hyg 102(Suppl 1):S145–S151.
    621.
    Moore RA, DeShazer D, Reckseidler S, Weissman A, Woods DE. 1999. Efflux-mediated aminoglycoside and macrolide resistance in Burkholderia pseudomallei. Antimicrob Agents Chemother 43:465–470.
    622.
    Chan YY, Chua KL. 2005. The Burkholderia pseudomallei BpeAB-OprB efflux pump: expression and impact on quorum sensing and virulence. J Bacteriol 187:4707–4719.
    623.
    Kumar A, Chua KL, Schweizer HP. 2006. Method for regulated expression of single-copy efflux pump genes in a surrogate Pseudomonas aeruginosa strain: identification of the BpeEF-OprC chloramphenicol and trimethoprim efflux pump of Burkholderia pseudomallei 1026b. Antimicrob Agents Chemother 50:3460–3463.
    624.
    Podnecky NL, Wuthiekanun V, Peacock SJ, Schweizer HP. 2013. The BpeEF-OprC efflux pump is responsible for widespread trimethoprim resistance in clinical and environmental Burkholderia pseudomallei isolates. Antimicrob Agents Chemother 57:4381–4386.
    625.
    Podin Y, Sarovich DS, Price EP, Kaestli M, Mayo M, Hii K, Ngian H, Wong S, Wong I, Wong J, Mohan A, Ooi M, Fam T, Wong J, Tuanyok A, Keim P, Giffard PM, Currie BJ. 2014. Burkholderia pseudomallei isolates from Sarawak, Malaysian Borneo, are predominantly susceptible to aminoglycosides and macrolides. Antimicrob Agents Chemother 58:162–166.
    626.
    Howard K, Inglis TJ. 2003. Novel selective medium for isolation of Burkholderia pseudomallei. J Clin Microbiol 41:3312–3316.
    627.
    Biot FV, Lopez MM, Poyot T, Neulat-Ripoll F, Lignon S, Caclard A, Thibault FM, Peinnequin A, Pagès JM, Valade E. 2013. Interplay between three RND efflux pumps in doxycycline-selected strains of Burkholderia thailandensis. PLoS One 8:e84068.
    628.
    Li X-Z, Barré N, Poole K. 2000. Influence of the MexA-MexB-OprM multidrug efflux system on expression of the MexC-MexD-OprJ and MexE-MexF-OprN multidrug efflux systems in Pseudomonas aeruginosa. J Antimicrob Chemother 46:885–893.
    629.
    Blair JM, Smith HE, Ricci V, Lawler AJ, Thompson LJ, Piddock LJ. 2015. Expression of homologous RND efflux pump genes is dependent upon AcrB expression: implications for efflux and virulence inhibitor design. J Antimicrob Chemother 70:424–431.
    630.
    Sánchez P, Le U, Martínez JL. 2003. The efflux pump inhibitor Phe-Arg-β-naphthylamide does not abolish the activity of the Stenotrophomonas maltophilia SmeDEF multidrug efflux pump. J Antimicrob Chemother 51:1042–1045.
    631.
    Unemo M, Shafer WM. 2014. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin Microbiol Rev 27:587–613.
    632.
    Young JD, Blake M, Mauro A, Cohn ZA. 1983. Properties of the major outer membrane protein from Neisseria gonorrhoeae incorporated into model lipid membranes. Proc Natl Acad Sci U S A 80:3831–3835.
    633.
    Pan W, Spratt BG. 1994. Regulation of the permeability of the gonococcal cell envelope by the mtr system. Mol Microbiol 11:769–775.
    634.
    Olesky M, Zhao S, Rosenberg RL, Nicholas RA. 2006. Porin-mediated antibiotic resistance in Neisseria gonorrhoeae: ion, solute, and antibiotic permeation through PIB proteins with penB mutations. J Bacteriol 188:2300–2308.
    635.
    Shafer WM, Folster JP. 2006. Towards an understanding of chromosomally mediated penicillin resistance in Neisseria gonorrhoeae: evidence for a porin-efflux pump collaboration. J Bacteriol 188:2297–2299.
    636.
    Camara J, Serra J, Ayats J, Bastida T, Carnicer-Pont D, Andreu A, Ardanuy C. 2012. Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain. J Antimicrob Chemother 67:1858–1860.
    637.
    Rouquette C, Harmon JB, Shafer WM. 1999. Induction of the mtrCDE-encoded efflux pump system of Neisseria gonorrhoeae requires MtrA, an AraC-like protein. Mol Microbiol 33:651–658.
    638.
    Shafer WM, Qu X, Waring AJ, Lehrer RI. 1998. Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family. Proc Natl Acad Sci U S A 95:1829–1833.
    639.
    Hagman KE, Pan W, Spratt BG, Balthazar JT, Judd RC, Shafer WM. 1995. Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents is modulated by the mtrRCDE efflux system. Microbiology 141:611–622.
    640.
    Jerse AE, Sharma ND, Simms AN, Crow ET, Snyder LA, Shafer WM. 2003. A gonococcal efflux pump system enhances bacterial survival in a female mouse model of genital tract infection. Infect Immun 71:5576–5582.
    641.
    Warner DM, Shafer WM, Jerse AE. 2008. Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC-MtrD-MtrE efflux pump system confer different levels of antimicrobial resistance and in vivo fitness. Mol Microbiol 70:462–478.
    642.
    Ohneck EA, Goytia M, Rouquette-Loughlin CE, Joseph SJ, Read TD, Jerse AE, Shafer WM. 2015. Overproduction of the MtrCDE efflux pump in Neisseria gonorrhoeae produces unexpected changes in cellular transcription patterns. Antimicrob Agents Chemother 59:724–726.
    643.
    Bolla JR, Su CC, Do SV, Radhakrishnan A, Kumar N, Long F, Chou TH, Delmar JA, Lei HT, Rajashankar KR, Shafer WM, Yu EW. 2014. Crystal structure of the Neisseria gonorrhoeae MtrD inner membrane multidrug efflux pump. PLoS One 9:e97903.
    644.
    Lei HT, Chou TH, Su CC, Bolla JR, Kumar N, Radhakrishnan A, Long F, Delmar JA, Do SV, Rajashankar KR, Shafer WM, Yu EW. 2014. Crystal structure of the open state of the Neisseria gonorrhoeae MtrE outer membrane channel. PLoS One 9:e97475.
    645.
    Lee EH, Hill SA, Napier R, Shafer WM. 2006. Integration host factor is required for FarR repression of the farAB-encoded efflux pump of Neisseria gonorrhoeae. Mol Microbiol 60:1381–1400.
    646.
    Morse SA, Lysko PG, McFarland L, Knapp JS, Sandstrom E, Critchlow C, Holmes KK. 1982. Gonococcal strains from homosexual men have outer membranes with reduced permeability to hydrophobic molecules. Infect Immun 37:432–438.
    647.
    Golparian D, Shafer WM, Ohnishi M, Unemo M. 2014. Importance of multidrug efflux pumps in the antimicrobial resistance property of clinical multidrug-resistant isolates of Neisseria gonorrhoeae. Antimicrob Agents Chemother 58:3556–3559.
    648.
    Luna VA, Cousin S, Jr, Whittington WL, Roberts MC. 2000. Identification of the conjugative mef gene in clinical Acinetobacter junii and Neisseria gonorrhoeae isolates. Antimicrob Agents Chemother 44:2503–2506.
    649.
    Campbell BJ, Engel AS, Porter ML, Takai K. 2006. The versatile epsilon-proteobacteria: key players in sulphidic habitats. Nat Rev Microbiol 4:458–468.
    650.
    Zhuang J, Engel A, Pagès JM, Bolla JM. 1997. The Campylobacter jejuni porin trimers pack into different lattice types when reconstituted in the presence of lipid. Eur J Biochem 244:575–579.
    651.
    Labesse G, Garnotel E, Bonnel S, Dumas C, Pagès JM, Bolla JM. 2001. MOMP, a divergent porin from Campylobacter: cloning and primary structural characterization. Biochem Biophys Res Commun 280:380–387.
    652.
    Page WJ, Huyer G, Huyer M, Worobec EA. 1989. Characterization of the porins of Campylobacter jejuni and Campylobacter coli and implications for antibiotic susceptibility. Antimicrob Agents Chemother 33:297–303.
    653.
    De E, Jullien M, Labesse G, Pagès JM, Molle G, Bolla JM. 2000. MOMP (major outer membrane protein) of Campylobacter jejuni; a versatile pore-forming protein. FEBS Lett 469:93–97.
    654.
    Lin J, Michel LO, Zhang Q. 2002. CmeABC functions as a multidrug efflux system in Campylobacter jejuni. Antimicrob Agents Chemother 46:2124–2131.
    655.
    Lin J, Sahin O, Michel LO, Zhang Q. 2003. Critical role of multidrug efflux pump CmeABC in bile resistance and in vivo colonization of Campylobacter jejuni. Infect Immun 71:4250–4259.
    656.
    Luo N, Sahin O, Lin J, Michel LO, Zhang Q. 2003. In vivo selection of Campylobacter isolates with high levels of fluoroquinolone resistance associated with gyrA mutations and the function of the CmeABC efflux pump. Antimicrob Agents Chemother 47:390–394.
    657.
    Randall LP, Ridley AM, Cooles SW, Sharma M, Sayers AR, Pumbwe L, Newell DG, Piddock LJ, Woodward MJ. 2003. Prevalence of multiple antibiotic resistance in 443 Campylobacter spp. isolated from humans and animals. J Antimicrob Chemother 52:507–510.
    658.
    Cagliero C, Mouline C, Cloeckaert A, Payot S. 2006. Synergy between efflux pump CmeABC and modifications in ribosomal proteins L4 and L22 in conferring macrolide resistance in Campylobacter jejuni and Campylobacter coli. Antimicrob Agents Chemother 50:3893–3896.
    659.
    Yan M, Sahin O, Lin J, Zhang Q. 2006. Role of the CmeABC efflux pump in the emergence of fluoroquinolone-resistant Campylobacter under selection pressure. J Antimicrob Chemother 58:1154–1159.
    660.
    Piddock LJ, Griggs D, Johnson MM, Ricci V, Elviss NC, Williams LK, Jorgensen F, Chisholm SA, Lawson AJ, Swift C, Humphrey TJ, Owen RJ. 2008. Persistence of Campylobacter species, strain types, antibiotic resistance and mechanisms of tetracycline resistance in poultry flocks treated with chlortetracycline. J Antimicrob Chemother 62:303–315.
    661.
    Rozynek E, Mackiw E, Kaminska W, Tomczuk K, Antos-Bielska M, Dzierzanowska-Fangrat K, Korsak D. 2013. Emergence of macrolide-resistant Campylobacter strains in chicken meat in Poland and the resistance mechanisms involved. Foodborne Pathog Dis 10:655–660.
    662.
    Akiba M, Lin J, Barton YW, Zhang Q. 2006. Interaction of CmeABC and CmeDEF in conferring antimicrobial resistance and maintaining cell viability in Campylobacter jejuni. J Antimicrob Chemother 57:52–60.
    663.
    Mu Y, Shen Z, Jeon B, Dai L, Zhang Q. 2013. Synergistic effects of anti-CmeA and anti-CmeB peptide nucleic acids on sensitizing Campylobacter jejuni to antibiotics. Antimicrob Agents Chemother 57:4575–4577.
    664.
    Oh E, Zhang Q, Jeon B. 2014. Target optimization for peptide nucleic acid (PNA)-mediated antisense inhibition of the CmeABC multidrug efflux pump in Campylobacter jejuni. J Antimicrob Chemother 69:375–380.
    665.
    Runti G, del Carmen Lopez Ruiz M, Stoilova T, Hussain R, Jennions M, Choudhury HG, Benincasa M, Gennaro R, Beis K, Scocchi M. 2013. Functional characterization of SbmA, a bacterial inner membrane transporter required for importing the antimicrobial peptide Bac7(1-35). J Bacteriol 195:5343–5351.
    666.
    Riedel CT, Cohn MT, Stabler RA, Wren B, Brondsted L. 2012. Cellular response of Campylobacter jejuni to trisodium phosphate. Appl Environ Microbiol 78:1411–1415.
    667.
    Lin J, Yan M, Sahin O, Pereira S, Chang YJ, Zhang Q. 2007. Effect of macrolide usage on emergence of erythromycin-resistant Campylobacter isolates in chickens. Antimicrob Agents Chemother 51:1678–1686.
    668.
    Hao H, Yuan Z, Shen Z, Han J, Sahin O, Liu P, Zhang Q. 2013. Mutational and transcriptomic changes involved in the development of macrolide resistance in Campylobacter jejuni. Antimicrob Agents Chemother 57:1369–1378.
    669.
    Hao H, Dai M, Wang Y, Peng D, Liu Z, Yuan Z. 2009. 23S rRNA mutation A2074C conferring high-level macrolide resistance and fitness cost in Campylobacter jejuni. Microb Drug Resist 15:239–244.
    670.
    Almofti YA, Dai M, Sun Y, Haihong H, Yuan Z. 2011. Impact of erythromycin resistance on the virulence properties and fitness of Campylobacter jejuni. Microb Pathog 50:336–342.
    671.
    Luangtongkum T, Shen Z, Seng VW, Sahin O, Jeon B, Liu P, Zhang Q. 2012. Impaired fitness and transmission of macrolide-resistant Campylobacter jejuni in its natural host. Antimicrob Agents Chemother 56:1300–1308.
    672.
    Xia Q, Muraoka WT, Shen Z, Sahin O, Wang H, Wu Z, Liu P, Zhang Q. 2013. Adaptive mechanisms of Campylobacter jejuni to erythromycin treatment. BMC Microbiol 13:133.
    673.
    Jeon B, Wang Y, Hao H, Barton YW, Zhang Q. 2011. Contribution of CmeG to antibiotic and oxidative stress resistance in Campylobacter jejuni. J Antimicrob Chemother 66:79–85.
    674.
    Shen Z, Luangtongkum T, Qiang Z, Jeon B, Wang L, Zhang Q. 2014. Identification of a novel membrane transporter mediating resistance to organic arsenic in Campylobacter jejuni. Antimicrob Agents Chemother 58:2021–2029.
    675.
    Polk DB, Peek RM, Jr. 2010. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer 10:403–414.
    676.
    Megraud F, Lehours P. 2007. Helicobacter pylori detection and antimicrobial susceptibility testing. Clin Microbiol Rev 20:280–322.
    677.
    Graham DY, Fischbach L. 2010. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 59:1143–1153.
    678.
    Megraud F, Coenen S, Versporten A, Kist M, Lopez-Brea M, Hirschl AM, Andersen LP, Goossens H, Glupczynski Y. 2013. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut 62:34–42.
    679.
    Tomb JF, White O, Kerlavage AR, Clayton RA, Sutton GG, Fleischmann RD, Ketchum KA, Klenk HP, Gill S, Dougherty BA, Nelson K, Quackenbush J, Zhou L, Kirkness EF, Peterson S, Loftus B, Richardson D, Dodson R, Khalak HG, Glodek A, McKenney K, Fitzegerald LM, Lee N, Adams MD, Hickey EK, Berg DE, Gocayne JD, Utterback TR, Peterson JD, Kelley JM, Cotton MD, Weidman JM, Fujii C, Bowman C, Watthey L, Wallin E, Hayes WS, Borodovsky M, Karp PD, Smith HO, Fraser CM, Venter JC. 1997. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388:539–547.
    680.
    Doig P, Exner MM, Hancock RE, Trust TJ. 1995. Isolation and characterization of a conserved porin protein from Helicobacter pylori. J Bacteriol 177:5447–5452.
    681.
    Bina JE, Alm RA, Uria-Nickelsen M, Thomas SR, Trust TJ, Hancock RE. 2000. Helicobacter pylori uptake and efflux: basis for intrinsic susceptibility to antibiotics in vitro. Antimicrob Agents Chemother 44:248–254.
    682.
    Liu ZQ, Zheng PY, Yang PC. 2008. Efflux pump gene hefA of Helicobacter pylori plays an important role in multidrug resistance. World J Gastroenterol 14:5217–5222.
    683.
    Kutschke A, de Jonge BL. 2005. Compound efflux in Helicobacter pylori. Antimicrob Agents Chemother 49:3009–3010.
    684.
    Stahler FN, Odenbreit S, Haas R, Wilrich J, Van Vliet AH, Kusters JG, Kist M, Bereswill S. 2006. The novel Helicobacter pylori CznABC metal efflux pump is required for cadmium, zinc, and nickel resistance, urease modulation, and gastric colonization. Infect Immun 74:3845–3852.
    685.
    van Amsterdam K, Bart A, van der Ende A. 2005. A Helicobacter pylori TolC efflux pump confers resistance to metronidazole. Antimicrob Agents Chemother 49:1477–1482.
    686.
    Tsugawa H, Suzuki H, Muraoka H, Ikeda F, Hirata K, Matsuzaki J, Saito Y, Hibi T. 2011. Enhanced bacterial efflux system is the first step to the development of metronidazole resistance in Helicobacter pylori. Biochem Biophys Res Commun 404:656–660.
    687.
    Mehrabadi JF, Sirous M, Daryani NE, Eshraghi S, Akbari B, Shirazi MH. 2011. Assessing the role of the RND efflux pump in metronidazole resistance of Helicobacter pylori by RT-PCR assay. J Infect Dev Ctries 5:88–93.
    688.
    Trainor EA, Horton KE, Savage PB, Testerman TL, McGee DJ. 2011. Role of the HefC efflux pump in Helicobacter pylori cholesterol-dependent resistance to ceragenins and bile salts. Infect Immun 79:88–97.
    689.
    Qureshi NN, Gallaher B, Schiller NL. 2014. Evolution of amoxicillin resistance of Helicobacter pylori in vitro: characterization of resistance mechanisms. Microb Drug Resist 20:509–516.
    690.
    Iwamoto A, Tanahashi T, Okada R, Yoshida Y, Kikuchi K, Keida Y, Murakami Y, Yang L, Yamamoto K, Nishiumi S, Yoshida M, Azuma T. 2014. Whole-genome sequencing of clarithromycin resistant Helicobacter pylori characterizes unidentified variants of multidrug resistant efflux pump genes. Gut Pathog 6:27.
    691.
    Chiu HC, Lin TL, Yang JC, Wang JT. 2009. Synergistic effect of imp/ostA and msbA in hydrophobic drug resistance of Helicobacter pylori. BMC Microbiol 9:136.
    692.
    Morita Y, Tomida J, Kawamura Y. 2012. Multidrug efflux systems in Helicobacter cinaedi. Antibiotics 1:29–43.
    693.
    Wexler HM. 2007. Bacteroides: the good, the bad, and the nitty-gritty. Clin Microbiol Rev 20:593–621.
    694.
    Kobayashi Y, Kanazawa K, Nishino T. 1991. Transmembrane diffusion of hydrophobic antimicrobial agents and cell surface hydrophobicity in Bacteroides fragilis. FEMS Microbiol Lett 65:141–144.
    695.
    Cerdeno-Tarraga AM, Patrick S, Crossman LC, Blakely G, Abratt V, Lennard N, Poxton I, Duerden B, Harris B, Quail MA, Barron A, Clark L, Corton C, Doggett J, Holden MT, Larke N, Line A, Lord A, Norbertczak H, Ormond D, Price C, Rabbinowitsch E, Woodward J, Barrell B, Parkhill J. 2005. Extensive DNA inversions in the B. fragilis genome control variable gene expression. Science 307:1463–1465.
    696.
    Xu J, Bjursell MK, Himrod J, Deng S, Carmichael LK, Chiang HC, Hooper LV, Gordon JI. 2003. A genomic view of the human-Bacteroides thetaiotaomicron symbiosis. Science 299:2074–2076.
    697.
    Ueda O, Wexler HM, Hirai K, Shibata Y, Yoshimura F, Fujimura S. 2005. Sixteen homologs of the mex-type multidrug resistance efflux pump in Bacteroides fragilis. Antimicrob Agents Chemother 49:2807–2815.
    698.
    Pumbwe L, Chang A, Smith RL, Wexler HM. 2007. BmeRABC5 is a multidrug efflux system that can confer metronidazole resistance in Bacteroides fragilis. Microb Drug Resist 13:96–101.
    699.
    Cassone M, D'Andrea MM, Iannelli F, Oggioni MR, Rossolini GM, Pozzi G. 2006. DNA microarray for detection of macrolide resistance genes. Antimicrob Agents Chemother 50:2038–2041.
    700.
    Eitel Z, Soki J, Urban E, Nagy E, ESCMID Study Group on Anaerobic Infection. 2013. The prevalence of antibiotic resistance genes in Bacteroides fragilis group strains isolated in different European countries. Anaerobe 21:43–49.
    701.
    Husain F, Veeranagouda Y, Boente R, Tang K, Mulato G, Wexler HM. 2014. The Ellis Island effect: a novel mobile element in a multi-drug resistant clinical isolate includes a mosaic of resistance genes from Gram-positive bacteria. Mob Genet Elements 4:e29801.
    702.
    Sherrard LJ, Schaible B, Graham KA, McGrath SJ, McIlreavey L, Hatch J, Wolfgang MC, Muhlebach MS, Gilpin DF, Schneiders T, Elborn JS, Tunney MM. 2014. Mechanisms of reduced susceptibility and genotypic prediction of antibiotic resistance in Prevotella isolated from cystic fibrosis (CF) and non-CF patients. J Antimicrob Chemother 69:2690–2698.
    703.
    Davies J, Smith DI. 1978. Plasmid-determined resistance to antimicrobial agents. Annu Rev Microbiol 32:469–518.
    704.
    Li X-Z. 2005. Quinolone resistance in bacteria: emphasis on plasmid-mediated mechanisms. Int J Antimicrob Agents 25:453–463.
    705.
    Carattoli A. 2013. Plasmids and the spread of resistance. Int J Med Microbiol 303:298–304.
    706.
    Liu J, Keelan P, Bennett PM, Enne VI. 2009. Characterization of a novel macrolide efflux gene, mef(B), found linked to sul3 in porcine Escherichia coli. J Antimicrob Chemother 63:423–426.
    707.
    Cattoir V, Poirel L, Nordmann P. 2008. Plasmid-mediated quinolone resistance pump QepA2 in an Escherichia coli isolate from France. Antimicrob Agents Chemother 52:3801–3804.
    708.
    Hansen LH, Johannesen E, Burmolle M, Sorensen AH, Sorensen SJ. 2004. Plasmid-encoded multidrug efflux pump conferring resistance to olaquindox in Escherichia coli. Antimicrob Agents Chemother 48:3332–3337.
    709.
    Hansen LH, Jensen LB, Sorensen HI, Sorensen SJ. 2007. Substrate specificity of the OqxAB multidrug resistance pump in Escherichia coli and selected enteric bacteria. J Antimicrob Chemother 60:145–147.
    710.
    Chen X, Zhang W, Pan W, Yin J, Pan Z, Gao S, Jiao X. 2012. Prevalence of qnr, aac(6)-Ib-cr, qepA, and oqxAB in Escherichia coli isolates from humans, animals, and the environment. Antimicrob Agents Chemother 56:3423–3427.
    711.
    Xu X, Cui S, Zhang F, Luo Y, Gu Y, Yang B, Li F, Chen Q, Zhou G, Wang Y, Pang L, Lin L. 2014. Prevalence and characterization of cefotaxime and ciprofloxacin co-resistant Escherichia coli isolates in retail chicken carcasses and ground pork, China. Microb Drug Resist 20:73–81.
    712.
    Dotto G, Giacomelli M, Grilli G, Ferrazzi V, Carattoli A, Fortini D, Piccirillo A. 2014. High prevalence of oqxAB in Escherichia coli isolates from domestic and wild lagomorphs in Italy. Microb Drug Resist 20:118–123.
    713.
    Liu BT, Li L, Fang LX, Sun J, Liao XP, Yang QE, Huang T, Liu YH. 2014. Characterization of plasmids carrying oqxAB in blaCTX-M-negative Escherichia coli isolates from food-producing animals. Microb Drug Resist 20:641–650.
    714.
    Chandran SP, Diwan V, Tamhankar AJ, Joseph BV, Rosales-Klintz S, Mundayoor S, Lundborg CS, Macaden R. 2014. Detection of carbapenem resistance genes and cephalosporin, and quinolone resistance genes along with oqxAB gene in Escherichia coli in hospital wastewater: a matter of concern. J Appl Microbiol 117:984–995.
    715.
    Li L, Liao XP, Liu ZZ, Huang T, Li X, Sun J, Liu BT, Zhang Q, Liu YH. 2014. Co-spread of oqxAB and blaCTX-M-9G in non-Typhi Salmonella enterica isolates mediated by ST2-IncHI2 plasmids. Int J Antimicrob Agents 44:263–268.
    716.
    McHugh GL, Moellering RC, Hopkins CC, Swartz MN. 1975. Salmonella typhimurium resistant to silver nitrate, chloramphenicol, and ampicillin. Lancet i:235–240.
    717.
    Gupta A, Matsui K, Lo JF, Silver S. 1999. Molecular basis for resistance to silver cations in Salmonella. Nat Med 5:183–188.
    718.
    Li X-Z, Nikaido H, Williams KE. 1997. Silver-resistant mutants of Escherichia coli display active efflux of Ag+ and are deficient in porins. J Bacteriol 179:6127–6132.
    719.
    Szczepanowski R, Krahn I, Linke B, Goesmann A, Puhler A, Schluter A. 2004. Antibiotic multiresistance plasmid pRSB101 isolated from a wastewater treatment plant is related to plasmids residing in phytopathogenic bacteria and carries eight different resistance determinants including a multidrug transport system. Microbiology 150:3613–3630.
    720.
    Szczepanowski R, Linke B, Krahn I, Gartemann KH, Gutzkow T, Eichler W, Puhler A, Schluter A. 2009. Detection of 140 clinically relevant antibiotic-resistance genes in the plasmid metagenome of wastewater treatment plant bacteria showing reduced susceptibility to selected antibiotics. Microbiology 155:2306–2319.
    721.
    Norberg P, Bergstrom M, Hermansson M. 2014. Complete nucleotide sequence and analysis of two conjugative broad host range plasmids from a marine microbial biofilm. PLoS One 9:e92321.
    722.
    Dahlberg C, Linberg C, Torsvik VL, Hermansson M. 1997. Conjugative plasmids isolated from bacteria in marine environments show various degrees of homology to each other and are not closely related to well-characterized plasmids. Appl Environ Microbiol 63:4692–4697.
    723.
    Norberg P, Bergstrom M, Jethava V, Dubhashi D, Hermansson M. 2011. The IncP-1 plasmid backbone adapts to different host bacterial species and evolves through homologous recombination. Nat Commun 2:268.
    724.
    Poirel L, Ros A, Carricajo A, Berthelot P, Pozzetto B, Bernabeu S, Nordmann P. 2011. Extremely drug-resistant Citrobacter freundii isolate producing NDM-1 and other carbapenemases identified in a patient returning from India. Antimicrob Agents Chemother 55:447–448.
    725.
    Grkovic S, Brown MH, Skurray RA. 2002. Regulation of bacterial drug export systems. Microbiol Mol Biol Rev 66:671–701.
    726.
    Ma D, Alberti M, Lynch C, Nikaido H, Hearst JE. 1996. The local repressor AcrR plays a modulating role in the regulation of acrAB genes of Escherichia coli by global stress signals. Mol Microbiol 19:101–112.
    727.
    Cuthbertson L, Nodwell JR. 2013. The TetR family of regulators. Microbiol Mol Biol Rev 77:440–475.
    728.
    Li M, Gu R, Su CC, Routh MD, Harris KC, Jewell ES, McDermott G, Yu EW. 2007. Crystal structure of the transcriptional regulator AcrR from Escherichia coli. J Mol Biol 374:591–603.
    729.
    Su CC, Yu EW. 2007. Ligand-transporter interaction in the AcrB multidrug efflux pump determined by fluorescence polarization assay. FEBS Lett 581:4972–4976.
    730.
    Gu R, Li M, Su CC, Long F, Routh MD, Yang F, McDermott G, Yu EW. 2008. Conformational change of the AcrR regulator reveals a possible mechanism of induction. Acta Crystallogr Sect F Struct Biol Cryst Commun 64:584–588.
    731.
    Hirakawa H, Takumi-Kobayashi A, Theisen U, Hirata T, Nishino K, Yamaguchi A. 2008. AcrS/EnvR represses expression of the acrAB multidrug efflux genes in Escherichia coli. J Bacteriol 190:6276–6279.
    732.
    Nishino K, Yamaguchi A. 2004. Role of histone-like protein H-NS in multidrug resistance of Escherichia coli. J Bacteriol 186:1423–1429.
    733.
    Rahmati S, Yang S, Davidson AL, Zechiedrich EL. 2002. Control of the AcrAB multidrug efflux pump by quorum-sensing regulator SdiA. Mol Microbiol 43:677–685.
    734.
    Kim T, Duong T, Wu CA, Choi J, Lan N, Kang SW, Lokanath NK, Shin D, Hwang HY, Kim KK. 2014. Structural insights into the molecular mechanism of Escherichia coli SdiA, a quorum-sensing receptor. Acta Crystallogr D Biol Crystallogr 70:694–707.
    735.
    Nicoloff H, Perreten V, Levy SB. 2007. Increased genome instability in Escherichia coli lon mutants: relation to emergence of multiple-antibiotic-resistant (Mar) mutants caused by insertion sequence elements and large tandem genomic amplifications. Antimicrob Agents Chemother 51:1293–1303.
    736.
    McDermott PF, McMurry LM, Podglajen I, Dzink-Fox JL, Schneiders T, Draper MP, Levy SB. 2008. The marC gene of Escherichia coli is not involved in multiple antibiotic resistance. Antimicrob Agents Chemother 52:382–383.
    737.
    Alekshun MN, Levy SB, Mealy TR, Seaton BA, Head JF. 2001. The crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 A resolution. Nat Struct Biol 8:710–714.
    738.
    Gallegos MT, Schleif R, Bairoch A, Hofmann K, Ramos JL. 1997. Arac/XylS family of transcriptional regulators. Microbiol Mol Biol Rev 61:393–410.
    739.
    Rhee S, Martin RG, Rosner JL, Davies DR. 1998. A novel DNA-binding motif in MarA: the first structure for an AraC family transcriptional activator. Proc Natl Acad Sci U S A 95:10413–10418.
    740.
    Barbosa TM, Levy SB. 2000. Differential expression of over 60 chromosomal genes in Escherichia coli by constitutive expression of MarA. J Bacteriol 182:3467–3474.
    741.
    Martin RG, Rosner JL. 2011. Promoter discrimination at class I MarA regulon promoters mediated by glutamic acid 89 of the MarA transcriptional activator of Escherichia coli. J Bacteriol 193:506–515.
    742.
    Griffith KL, Shah IM, Wolf RE, Jr. 2004. Proteolytic degradation of Escherichia coli transcription activators SoxS and MarA as the mechanism for reversing the induction of the superoxide (SoxRS) and multiple antibiotic resistance (Mar) regulons. Mol Microbiol 51:1801–1816.
    743.
    McMurry LM, Oethinger M, Levy SB. 1998. Overexpression of marA, soxS, or acrAB produces resistance to triclosan in laboratory and clinical strains of Escherichia coli. FEMS Microbiol Lett 166:305–309.
    744.
    McMurry LM, Levy SB. 2013. Amino acid residues involved in inactivation of the Escherichia coli multidrug resistance repressor MarR by salicylate, 2,4-dinitrophenol, and plumbagin. FEMS Microbiol Lett 349:16–24.
    745.
    Hidalgo E, Ding H, Demple B. 1997. Redox signal transduction via iron-sulfur clusters in the SoxR transcription activator. Trends Biochem Sci 22:207–210.
    746.
    Rosenberg EY, Bertenthal D, Nilles ML, Bertrand KP, Nikaido H. 2003. Bile salts and fatty acids induce the expression of Escherichia coli AcrAB multidrug efflux pump through their interaction with Rob regulatory protein. Mol Microbiol 48:1609–1619.
    747.
    Kwon HJ, Bennik MH, Demple B, Ellenberger T. 2000. Crystal structure of the Escherichia coli Rob transcription factor in complex with DNA. Nat Struct Biol 7:424–430.
    748.
    Eguchi Y, Oshima T, Mori H, Aono R, Yamamoto K, Ishihama A, Utsumi R. 2003. Transcriptional regulation of drug efflux genes by EvgAS, a two-component system in Escherichia coli. Microbiology 149:2819–2828.
    749.
    Nishino K, Yamaguchi A. 2002. EvgA of the two-component signal transduction system modulates production of the yhiUV multidrug transporter in Escherichia coli. J Bacteriol 184:2319–2323.
    750.
    Eguchi Y, Itou J, Yamane M, Demizu R, Yamato F, Okada A, Mori H, Kato A, Utsumi R. 2007. B1500, a small membrane protein, connects the two-component systems EvgS/EvgA and PhoQ/PhoP in Escherichia coli. Proc Natl Acad Sci U S A 104:18712–18717.
    751.
    Zhang A, Rosner JL, Martin RG. 2008. Transcriptional activation by MarA, SoxS and Rob of two tolC promoters using one binding site: a complex promoter configuration for tolC in Escherichia coli. Mol Microbiol 69:1450–1455.
    752.
    Parker A, Gottesman S. 2014. Small RNA regulation of a multidrug efflux pump. FASEB J 28(Suppl):750.1.
    753.
    Yamada J, Yamasaki S, Hirakawa H, Hayashi-Nishino M, Yamaguchi A, Nishino K. 2010. Impact of the RNA chaperone Hfq on multidrug resistance in Escherichia coli. J Antimicrob Chemother 65:853–858.
    754.
    Kulesus RR, Diaz-Pérez K, Slechta ES, Eto DS, Mulvey MA. 2008. Impact of the RNA chaperone Hfq on the fitness and virulence potential of uropathogenic Escherichia coli. Infect Immun 76:3019–3026.
    755.
    Tavio MM, Aquili VD, Vila J, Poveda JB. 2014. Resistance to ceftazidime in Escherichia coli associated with AcrR, MarR and PBP3 mutations and overexpression of sdiA. J Med Microbiol 63:56–65.
    756.
    Hirakawa H, Inazumi Y, Masaki T, Hirata T, Yamaguchi A. 2005. Indole induces the expression of multidrug exporter genes in Escherichia coli. Mol Microbiol 55:1113–1126.
    757.
    Nishino K, Honda T, Yamaguchi A. 2005. Genome-wide analyses of Escherichia coli gene expression responsive to the BaeSR two-component regulatory system. J Bacteriol 187:1763–1772.
    758.
    Leblanc SK, Oates CW, Raivio TL. 2011. Characterization of the induction and cellular role of the BaeSR two-component envelope stress response of Escherichia coli. J Bacteriol 193:3367–3375.
    759.
    Pérez-Rodríguez R, Haitjema C, Huang Q, Nam KH, Bernardis S, Ke A, DeLisa MP. 2011. Envelope stress is a trigger of CRISPR RNA-mediated DNA silencing in Escherichia coli. Mol Microbiol 79:584–599.
    760.
    Guerrero P, Collao B, Morales EH, Calderon IL, Ipinza F, Parra S, Saavedra CP, Gil F. 2012. Characterization of the BaeSR two-component system from Salmonella Typhimurium and its role in ciprofloxacin-induced mdtA expression. Arch Microbiol 194:453–460.
    761.
    Zoetendal EG, Smith AH, Sundset MA, Mackie RI. 2008. The BaeSR two-component regulatory system mediates resistance to condensed tannins in Escherichia coli. Appl Environ Microbiol 74:535–539.
    762.
    Rosner JL, Martin RG. 2013. Reduction of cellular stress by TolC-dependent efflux pumps in Escherichia coli indicated by BaeSR and CpxARP activation of spy in efflux mutants. J Bacteriol 195:1042–1050.
    763.
    Hirakawa H, Inazumi Y, Senda Y, Kobayashi A, Hirata T, Nishino K, Yamaguchi A. 2006. N-Acetyl-D-glucosamine induces the expression of multidrug exporter genes, mdtEF, via catabolite activation in Escherichia coli. J Bacteriol 188:5851–5858.
    764.
    Nishino K, Senda Y, Yamaguchi A. 2008. The AraC-family regulator GadX enhances multidrug resistance in Escherichia coli by activating expression of mdtEF multidrug efflux genes. J Infect Chemother 14:23–29.
    765.
    Nishino K, Senda Y, Hayashi-Nishino M, Yamaguchi A. 2009. Role of the AraC-XylS family regulator YdeO in multi-drug resistance of Escherichia coli. J Antibiot (Tokyo) 62:251–257.
    766.
    Nishino K, Yamasaki S, Hayashi-Nishino M, Yamaguchi A. 2011. Effect of overexpression of small non-coding DsrA RNA on multidrug efflux in Escherichia coli. J Antimicrob Chemother 66:291–296.
    767.
    Sledjeski D, Gottesman S. 1995. A small RNA acts as an antisilencer of the H-NS-silenced rcsA gene of Escherichia coli. Proc Natl Acad Sci U S A 92:2003–2007.
    768.
    Deng Z, Shan Y, Pan Q, Gao X, Yan A. 2013. Anaerobic expression of the gadE-mdtEF multidrug efflux operon is primarily regulated by the two-component system ArcBA through antagonizing the H-NS mediated repression. Front Microbiol 4:194.
    769.
    Kobayashi A, Hirakawa H, Hirata T, Nishino K, Yamaguchi A. 2006. Growth phase-dependent expression of drug exporters in Escherichia coli and its contribution to drug tolerance. J Bacteriol 188:5693–5703.
    770.
    Randall LP, Woodward MJ. 2001. Multiple antibiotic resistance (mar) locus in Salmonella enterica serovar Typhimurium DT104. Appl Environ Microbiol 67:1190–1197.
    771.
    Eaves DJ, Ricci V, Piddock LJ. 2004. Expression of acrB, acrF, acrD, marA, and soxS in Salmonella enterica serovar Typhimurium: role in multiple antibiotic resistance. Antimicrob Agents Chemother 48:1145–1150.
    772.
    Koutsolioutsou A, Martins EA, White DG, Levy SB, Demple B. 2001. A soxRS-constitutive mutation contributing to antibiotic resistance in a clinical isolate of Salmonella enterica (serovar Typhimurium). Antimicrob Agents Chemother 45:38–43.
    773.
    Zheng J, Cui S, Meng J. 2009. Effect of transcriptional activators RamA and SoxS on expression of multidrug efflux pumps AcrAB and AcrEF in fluoroquinolone-resistant Salmonella Typhimurium. J Antimicrob Chemother 63:95–102.
    774.
    Nikaido E, Shirosaka I, Yamaguchi A, Nishino K. 2011. Regulation of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium in response to indole and paraquat. Microbiology 157:648–655.
    775.
    Bailey AM, Ivens A, Kingsley R, Cottell JL, Wain J, Piddock LJ. 2010. RamA, a member of the AraC/XylS family, influences both virulence and efflux in Salmonella enterica serovar Typhimurium. J Bacteriol 192:1607–1616.
    776.
    Baucheron S, Nishino K, Monchaux I, Canepa S, Maurel MC, Coste F, Roussel A, Cloeckaert A, Giraud E. 2014. Bile-mediated activation of the acrAB and tolC multidrug efflux genes occurs mainly through transcriptional derepression of ramA in Salmonella enterica serovar Typhimurium. J Antimicrob Chemother 69:2400–2406.
    777.
    Abouzeed YM, Baucheron S, Cloeckaert A. 2008. ramR mutations involved in efflux-mediated multidrug resistance in Salmonella enterica serovar Typhimurium. Antimicrob Agents Chemother 52:2428–2434.
    778.
    Baucheron S, Coste F, Canepa S, Maurel MC, Giraud E, Culard F, Castaing B, Roussel A, Cloeckaert A. 2012. Binding of the RamR repressor to wild-type and mutated promoters of the ramA gene involved in efflux-mediated multidrug resistance in Salmonella enterica serovar Typhimurium. Antimicrob Agents Chemother 56:942–948.
    779.
    Yamasaki S, Nikaido E, Nakashima R, Sakurai K, Fujiwara D, Fujii I, Nishino K. 2013. The crystal structure of multidrug-resistance regulator RamR with multiple drugs. Nat Commun 4:2078.
    780.
    Nikaido E, Yamaguchi A, Nishino K. 2008. AcrAB multidrug efflux pump regulation in Salmonella enterica serovar Typhimurium by RamA in response to environmental signals. J Biol Chem 283:24245–24253.
    781.
    Sun Y, Dai M, Hao H, Wang Y, Huang L, Almofti YA, Liu Z, Yuan Z. 2011. The role of RamA on the development of ciprofloxacin resistance in Salmonella enterica serovar Typhimurium. PLoS One 6:e23471.
    782.
    Lawler AJ, Ricci V, Busby SJ, Piddock LJ. 2013. Genetic inactivation of acrAB or inhibition of efflux induces expression of ramA. J Antimicrob Chemother 68:1551–1557.
    783.
    Ricci V, Blair JM, Piddock LJ. 2014. RamA, which controls expression of the MDR efflux pump AcrAB-TolC, is regulated by the Lon protease. J Antimicrob Chemother 69:643–650.
    784.
    Komatsu T, Ohta M, Kido N, Arakawa Y, Ito H, Mizuno T, Kato N. 1990. Molecular characterization of an Enterobacter cloacae gene (romA) which pleiotropically inhibits the expression of Escherichia coli outer membrane proteins. J Bacteriol 172:4082–4089.
    785.
    George AM, Hall RM, Stokes HW. 1995. Multidrug resistance in Klebsiella pneumoniae: a novel gene, ramA, confers a multidrug resistance phenotype in Escherichia coli. Microbiology 141:1909–1920.
    786.
    Ruzin A, Immermann FW, Bradford PA. 2008. Real-time PCR and statistical analyses of acrAB and ramA expression in clinical isolates of Klebsiella pneumoniae. Antimicrob Agents Chemother 52:3430–3432.
    787.
    Hentschke M, Wolters M, Sobottka I, Rohde H, Aepfelbacher M. 2010. ramR mutations in clinical isolates of Klebsiella pneumoniae with reduced susceptibility to tigecycline. Antimicrob Agents Chemother 54:2720–2723.
    788.
    Rosenblum R, Khan E, Gonzalez G, Hasan R, Schneiders T. 2011. Genetic regulation of the ramA locus and its expression in clinical isolates of Klebsiella pneumoniae. Int J Antimicrob Agents 38:39–45.
    789.
    Veleba M, Schneiders T. 2012. Tigecycline resistance can occur independently of the ramA gene in Klebsiella pneumoniae. Antimicrob Agents Chemother 56:4466–4467.
    790.
    Veleba M, Higgins PG, Gonzalez G, Seifert H, Schneiders T. 2012. Characterization of RarA, a novel AraC family multidrug resistance regulator in Klebsiella pneumoniae. Antimicrob Agents Chemother 56:4450–4458.
    791.
    De Majumdar S, Veleba M, Finn S, Fanning S, Schneiders T. 2013. Elucidating the regulon of multidrug resistance regulator RarA in Klebsiella pneumoniae. Antimicrob Agents Chemother 57:1603–1609.
    792.
    Bialek-Davenet S, Lavigne JP, Guyot K, Mayer N, Tournebize R, Brisse S, Leflon-Guibout V, Nicolas-Chanoine MH. 2015. Differential contribution of AcrAB and OqxAB efflux pumps to multidrug resistance and virulence in Klebsiella pneumoniae. J Antimicrob Chemother 70:81–88.
    793.
    Coudeyras S, Nakusi L, Charbonnel N, Forestier C. 2008. A tripartite efflux pump involved in gastrointestinal colonization by Klebsiella pneumoniae confers a tolerance response to inorganic acid. Infect Immun 76:4633–4641.
    794.
    Srinivasan VB, Vaidyanathan V, Mondal A, Rajamohan G. 2012. Role of the two component signal transduction system CpxAR in conferring cefepime and chloramphenicol resistance in Klebsiella pneumoniae NTUH-K2044. PLoS One 7:e33777.
    795.
    Srinivasan VB, Mondal A, Venkataramaiah M, Chauhan NK, Rajamohan G. 2013. Role of OxyRKP, a novel LysR-family transcriptional regulator, in antimicrobial resistance and virulence in Klebsiella pneumoniae. Microbiology 159:1301–1314.
    796.
    Evans K, Adewoye L, Poole K. 2001. MexR repressor of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa: identification of MexR binding sites in the mexA-mexR intergenic region. J Bacteriol 183:807–812.
    797.
    Sánchez P, Rojo F, Martínez JL. 2002. Transcriptional regulation of mexR, the repressor of Pseudomonas aeruginosa mexAB-oprM multidrug efflux pump. FEMS Microbiol Lett 207:63–68.
    798.
    Chen H, Hu J, Chen PR, Lan L, Li Z, Hicks LM, Dinner AR, He C. 2008. The Pseudomonas aeruginosa multidrug efflux regulator MexR uses an oxidation-sensing mechanism. Proc Natl Acad Sci U S A 105:13586–13591.
    799.
    Chen H, Yi C, Zhang J, Zhang W, Ge Z, Yang CG, He C. 2010. Structural insight into the oxidation-sensing mechanism of the antibiotic resistance of regulator MexR. EMBO Rep 11:685–690.
    800.
    Chang W, Small DA, Toghrol F, Bentley WE. 2005. Microarray analysis of Pseudomonas aeruginosa reveals induction of pyocin genes in response to hydrogen peroxide. BMC Genomics 6:115.
    801.
    Salunkhe P, Topfer T, Buer J, Tummler B. 2005. Genome-wide transcriptional profiling of the steady-state response of Pseudomonas aeruginosa to hydrogen peroxide. J Bacteriol 187:2565–2572.
    802.
    Cummins J, Reen FJ, Baysse C, Mooij MJ, O'Gara F. 2009. Subinhibitory concentrations of the cationic antimicrobial peptide colistin induce the pseudomonas quinolone signal in Pseudomonas aeruginosa. Microbiology 155:2826–2837.
    803.
    Whiteley M, Bangera MG, Bumgarner RE, Parsek MR, Teitzel GM, Lory S, Greenberg EP. 2001. Gene expression in Pseudomonas aeruginosa biofilms. Nature 413:860–864.
    804.
    Anderson GG, Moreau-Marquis S, Stanton BA, O'Toole GA. 2008. In vitro analysis of tobramycin-treated Pseudomonas aeruginosa biofilms on cystic fibrosis-derived airway epithelial cells. Infect Immun 76:1423–1433.
    805.
    Daigle DM, Cao L, Fraud S, Wilke MS, Pacey A, Klinoski R, Strynadka NC, Dean CR, Poole K. 2007. Protein modulator of multidrug efflux gene expression in Pseudomonas aeruginosa. J Bacteriol 189:5441–5451.
    806.
    Wilke MS, Heller M, Creagh AL, Haynes CA, McIntosh LP, Poole K, Strynadka NC. 2008. The crystal structure of MexR from Pseudomonas aeruginosa in complex with its antirepressor ArmR. Proc Natl Acad Sci U S A 105:14832–14837.
    807.
    Muller JF, Stevens AM, Craig J, Love NG. 2007. Transcriptome analysis reveals that multidrug efflux genes are upregulated to protect Pseudomonas aeruginosa from pentachlorophenol stress. Appl Environ Microbiol 73:4550–4558.
    808.
    Ghosh S, Cremers CM, Jakob U, Love NG. 2011. Chlorinated phenols control the expression of the multidrug resistance efflux pump MexAB-OprM in Pseudomonas aeruginosa by interacting with NalC. Mol Microbiol 79:1547–1556.
    809.
    Starr LM, Fruci M, Poole K. 2012. Pentachlorophenol induction of the Pseudomonas aeruginosa mexAB-oprM efflux operon: involvement of repressors NalC and MexR and the antirepressor ArmR. PLoS One 7:e32684.
    810.
    Morita Y, Cao L, Gould G, Avison MB, Poole K. 2006. nalD encodes a second repressor of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa. J Bacteriol 188:8649–8654.
    811.
    Terán W, Krell T, Ramos JL, Gallegos MT. 2006. Effector-repressor interactions, binding of a single effector molecule to the operator-bound TtgR homodimer mediates derepression. J Biol Chem 281:7102–7109.
    812.
    Yu J, Chen W, Wu C, Chen H. 2014. PEG-protein interaction induced contraction of NalD chains. PLoS One 9:e96616.
    813.
    Jimenez PN, Koch G, Thompson JA, Xavier KB, Cool RH, Quax WJ. 2012. The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol Mol Biol Rev 76:46–65.
    814.
    Maseda H, Sawada I, Saito K, Uchiyama H, Nakae T, Nomura N. 2004. Enhancement of the mexAB-oprM efflux pump expression by a quorum-sensing autoinducer and its cancellation by a regulator, MexT, of the mexEF-oprN efflux pump operon in Pseudomonas aeruginosa. Antimicrob Agents Chemother 48:1320–1328.
    815.
    Sawada I, Maseda H, Nakae T, Uchiyama H, Nomura N. 2004. A quorum-sensing autoinducer enhances the mexAB-oprM efflux-pump expression without the MexR-mediated regulation in Pseudomonas aeruginosa. Microbiol Immunol 48:435–439.
    816.
    Balasubramanian D, Schneper L, Merighi M, Smith R, Narasimhan G, Lory S, Mathee K. 2012. The regulatory repertoire of Pseudomonas aeruginosa AmpC β-lactamase regulator AmpR includes virulence genes. PLoS One 7:e34067.
    817.
    Brooun A, Liu S, Lewis K. 2000. A dose-response study of antibiotic resistance in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 44:640–646.
    818.
    Sivaneson M, Mikkelsen H, Ventre I, Bordi C, Filloux A. 2011. Two-component regulatory systems in Pseudomonas aeruginosa: an intricate network mediating fimbrial and efflux pump gene expression. Mol Microbiol 79:1353–1366.
    819.
    Liao J, Schurr MJ, Sauer K. 2013. The MerR-like regulator BrlR confers biofilm tolerance by activating multidrug efflux pumps in Pseudomonas aeruginosa biofilms. J Bacteriol 195:3352–3363.
    820.
    Liao J, Sauer K. 2012. The MerR-like transcriptional regulator BrlR contributes to Pseudomonas aeruginosa biofilm tolerance. J Bacteriol 194:4823–4836.
    821.
    Chambers JR, Liao J, Schurr MJ, Sauer K. 2014. BrlR from Pseudomonas aeruginosa is a c-di-GMP-responsive transcription factor. Mol Microbiol 92:471–487.
    822.
    Gupta K, Marques CN, Petrova OE, Sauer K. 2013. Antimicrobial tolerance of Pseudomonas aeruginosa biofilms is activated during an early developmental stage and requires the two-component hybrid SagS. J Bacteriol 195:4975–4987.
    823.
    Gupta K, Liao J, Petrova OE, Cherny KE, Sauer K. 2014. Elevated levels of the second messenger c-di-GMP contribute to antimicrobial resistance of Pseudomonas aeruginosa. Mol Microbiol 92:488–506.
    824.
    Pamp SJ, Gjermansen M, Johansen HK, Tolker-Nielsen T. 2008. Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa biofilms is linked to metabolically active cells, and depends on the pmr and mexAB-oprM genes. Mol Microbiol 68:223–240.
    825.
    Matsuo Y, Eda S, Gotoh N, Yoshihara E, Nakae T. 2004. MexZ-mediated regulation of mexXY multidrug efflux pump expression in Pseudomonas aeruginosa by binding on the mexZ-mexX intergenic DNA. FEMS Microbiol Lett 238:23–28.
    826.
    Yamamoto M, Ueda A, Kudo M, Matsuo Y, Fukushima J, Nakae T, Kaneko T, Ishigatsubo Y. 2009. Role of MexZ and PA5471 in transcriptional regulation of mexXY in Pseudomonas aeruginosa. Microbiology 155:3312–3321.
    827.
    Hay T, Fraud S, Lau CH, Gilmour C, Poole K. 2013. Antibiotic inducibility of the mexXY multidrug efflux operon of Pseudomonas aeruginosa: involvement of the MexZ anti-repressor ArmZ. PLoS One 8:e56858.
    828.
    Morita Y, Gilmour C, Metcalf D, Poole K. 2009. Translational control of the antibiotic inducibility of the PA5471 gene required for mexXY multidrug efflux gene expression in Pseudomonas aeruginosa. J Bacteriol 191:4966–4975.
    829.
    Lee S, Hinz A, Bauerle E, Angermeyer A, Juhaszova K, Kaneko Y, Singh PK, Manoil C. 2009. Targeting a bacterial stress response to enhance antibiotic action. Proc Natl Acad Sci U S A 106:14570–14575.
    830.
    Lau CH, Fraud S, Jones M, Peterson SN, Poole K. 2013. Mutational activation of the AmgRS two-component system in aminoglycoside-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 57:2243–2251.
    831.
    Lau CH, Krahn T, Gilmour C, Mullen E, Poole K. 2015. AmgRS-mediated envelope stress-inducible expression of the mexXY multidrug efflux operon of Pseudomonas aeruginosa. Microbiologyopen 4:121–135.
    832.
    McLaughlin HP, Caly DL, McCarthy Y, Ryan RP, Dow JM. 2012. An orphan chemotaxis sensor regulates virulence and antibiotic tolerance in the human pathogen Pseudomonas aeruginosa. PLoS One 7:e42205.
    833.
    Fernández L, Gooderham WJ, Bains M, McPhee JB, Wiegand I, Hancock RE. 2010. Adaptive resistance to the “last hope” antibiotics polymyxin B and colistin in Pseudomonas aeruginosa is mediated by the novel two-component regulatory system ParR-ParS. Antimicrob Agents Chemother 54:3372–3382.
    834.
    Purssell A, Poole K. 2013. Functional characterization of the NfxB repressor of the mexCD-oprJ multidrug efflux operon of Pseudomonas aeruginosa. Microbiology 159:2058–2073.
    835.
    Purssell A, Fruci M, Mikalauskas A, Gilmour C, Poole K. 2015. EsrC, an envelope stress-regulated repressor of the mexCD-oprJ multidrug efflux operon in Pseudomonas aeruginosa. Environ Microbiol 17:186–198.
    836.
    Köhler T, Epp SF, Curty LK, Pechère JC. 1999. Characterization of MexT, the regulator of the MexE-MexF-OprN multidrug efflux system of Pseudomonas aeruginosa. J Bacteriol 181:6300–6305.
    837.
    Chuanchuen R, Gaynor JB, Karkhoff-Schweizer R, Schweizer HP. 2005. Molecular characterization of MexL, the transcriptional repressor of the mexJK multidrug efflux operon in Pseudomonas aeruginosa. Antimicrob Agents Chemother 49:1844–1851.
    838.
    Monti MR, Morero NR, Miguel V, Argarana CE. 2013. nfxB as a novel target for analysis of mutation spectra in Pseudomonas aeruginosa. PLoS One 8:e66236.
    839.
    Mandsberg LF, Ciofu O, Kirkby N, Christiansen LE, Poulsen HE, Hoiby N. 2009. Antibiotic resistance in Pseudomonas aeruginosa strains with increased mutation frequency due to inactivation of the DNA oxidative repair system. Antimicrob Agents Chemother 53:2483–2491.
    840.
    Nde CW, Jang HJ, Toghrol F, Bentley WE. 2009. Global transcriptomic response of Pseudomonas aeruginosa to chlorhexidine diacetate. Environ Sci Technol 43:8406–8415.
    841.
    Ochs MM, McCusker MP, Bains M, Hancock RE. 1999. Negative regulation of the Pseudomonas aeruginosa outer membrane porin OprD selective for imipenem and basic amino acids. Antimicrob Agents Chemother 43:1085–1090.
    842.
    Tian ZX, Mac Aogain M, O'Connor HF, Fargier E, Mooij MJ, Adams C, Wang YP, O'Gara F. 2009. MexT modulates virulence determinants in Pseudomonas aeruginosa independent of the MexEF-OprN efflux pump. Microb Pathog 47:237–241.
    843.
    Tian ZX, Fargier E, Mac Aogain M, Adams C, Wang YP, O'Gara F. 2009. Transcriptome profiling defines a novel regulon modulated by the LysR-type transcriptional regulator MexT in Pseudomonas aeruginosa. Nucleic Acids Res 37:7546–7559.
    844.
    Lister PD, Wolter DJ, Hanson ND. 2009. Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin Microbiol Rev 22:582–610.
    845.
    Maseda H, Saito K, Nakajima A, Nakae T. 2000. Variation of the mexT gene, a regulator of the MexEF-oprN efflux pump expression in wild-type strains of Pseudomonas aeruginosa. FEMS Microbiol Lett 192:107–112.
    846.
    Sobel ML, Neshat S, Poole K. 2005. Mutations in PA2491 (mexS) promote MexT-dependent mexEF-oprN expression and multidrug resistance in a clinical strain of Pseudomonas aeruginosa. J Bacteriol 187:1246–1253.
    847.
    Fetar H, Gilmour C, Klinoski R, Daigle DM, Dean CR, Poole K. 2011. mexEF-oprN multidrug efflux operon of Pseudomonas aeruginosa: regulation by the MexT activator in response to nitrosative stress and chloramphenicol. Antimicrob Agents Chemother 55:508–514.
    848.
    Jin Y, Yang H, Qiao M, Jin S. 2011. MexT regulates the type III secretion system through MexS and PtrC in Pseudomonas aeruginosa. J Bacteriol 193:399–410.
    849.
    Fargier E, Mac Aogain M, Mooij MJ, Woods DF, Morrissey JP, Dobson AD, Adams C, O'Gara F. 2012. MexT functions as a redox-responsive regulator modulating disulfide stress resistance in Pseudomonas aeruginosa. J Bacteriol 194:3502–3511.
    850.
    Uwate M, Ichise YK, Shirai A, Omasa T, Nakae T, Maseda H. 2013. Two routes of MexS-MexT-mediated regulation of MexEF-OprN and MexAB-OprM efflux pump expression in Pseudomonas aeruginosa. Microbiol Immunol 57:263–272.
    851.
    Frisk A, Schurr JR, Wang G, Bertucci DC, Marrero L, Hwang SH, Hassett DJ, Schurr MJ. 2004. Transcriptome analysis of Pseudomonas aeruginosa after interaction with human airway epithelial cells. Infect Immun 72:5433–5438.
    852.
    Vallet I, Diggle SP, Stacey RE, Camara M, Ventre I, Lory S, Lazdunski A, Williams P, Filloux A. 2004. Biofilm formation in Pseudomonas aeruginosa: fimbrial cup gene clusters are controlled by the transcriptional regulator MvaT. J Bacteriol 186:2880–2890.
    853.
    Castang S, McManus HR, Turner KH, Dove SL. 2008. H-NS family members function coordinately in an opportunistic pathogen. Proc Natl Acad Sci U S A 105:18947–18952.
    854.
    Castang S, Dove SL. 2012. Basis for the essentiality of H-NS family members in Pseudomonas aeruginosa. J Bacteriol 194:5101–5109.
    855.
    Westfall LW, Carty NL, Layland N, Kuan P, Colmer-Hamood JA, Hamood AN. 2006. mvaT mutation modifies the expression of the Pseudomonas aeruginosa multidrug efflux operon mexEF-oprN. FEMS Microbiol Lett 255:247–254.
    856.
    Kumari H, Balasubramanian D, Zincke D, Mathee K. 2014. Role of Pseudomonas aeruginosa AmpR on β-lactam and non-β-lactam transient cross resistance upon pre-exposure to sub-inhibitory concentrations of antibiotics. J Med Microbiol 63:544–555.
    857.
    Caille O, Rossier C, Perron K. 2007. A copper-activated two-component system interacts with zinc and imipenem resistance in Pseudomonas aeruginosa. J Bacteriol 189:4561–4568.
    858.
    Marchand I, Damier-Piolle L, Courvalin P, Lambert T. 2004. Expression of the RND-type efflux pump AdeABC in Acinetobacter baumannii is regulated by the AdeRS two-component system. Antimicrob Agents Chemother 48:3298–3304.
    859.
    Lopes BS, Amyes SG. 2013. Insertion sequence disruption of adeR and ciprofloxacin resistance caused by efflux pumps and gyrA and parC mutations in Acinetobacter baumannii. Int J Antimicrob Agents 41:117–121.
    860.
    Sun JR, Perng CL, Lin JC, Yang YS, Chan MC, Chang TY, Lin FM, Chiueh TS. 2014. AdeRS combination codes differentiate the response to efflux pump inhibitors in tigecycline-resistant isolates of extensively drug-resistant Acinetobacter baumannii. Eur J Clin Microbiol Infect Dis 33:2141–2147.
    861.
    Yoon EJ, Courvalin P, Grillot-Courvalin C. 2013. RND-type efflux pumps in multidrug-resistant clinical isolates of Acinetobacter baumannii: major role for AdeABC overexpression and AdeRS mutations. Antimicrob Agents Chemother 57:2989–2995.
    862.
    Hua X, Chen Q, Li X, Yu Y. 2014. Global transcriptional response of Acinetobacter baumannii to a subinhibitory concentration of tigecycline. Int J Antimicrob Agents 44:337–344.
    863.
    Sánchez P, Alonso A, Martínez JL. 2002. Cloning and characterization of SmeT, a repressor of the Stenotrophomonas maltophilia multidrug efflux pump SmeDEF. Antimicrob Agents Chemother 46:3386–3393.
    864.
    Hernández A, Maté MJ, Sánchez-Diaz PC, Romero A, Rojo F, Martínez JL. 2009. Structural and functional analysis of SmeT, the repressor of the Stenotrophomonas maltophilia multidrug efflux pump SmeDEF. J Biol Chem 284:14428–14438.
    865.
    Hernández A, Ruiz FM, Romero A, Martínez JL. 2011. The binding of triclosan to SmeT, the repressor of the multidrug efflux pump SmeDEF, induces antibiotic resistance in Stenotrophomonas maltophilia. PLoS Pathog 7:e1002103.
    866.
    García-León G, Hernández A, Hernando-Amado S, Alavi P, Berg G, Martínez JL. 2014. A function of the major quinolone resistance determinant of Stenotrophomonas maltophilia SmeDEF is the colonization of the roots of the plants. Appl Environ Microbiol 80:4559–4565.
    867.
    Hoffmann KM, Williams D, Shafer WM, Brennan RG. 2005. Characterization of the multiple transferable resistance repressor, MtrR, from Neisseria gonorrhoeae. J Bacteriol 187:5008–5012.
    868.
    Folster JP, Johnson PJ, Jackson L, Dhulipali V, Dyer DW, Shafer WM. 2009. MtrR modulates rpoH expression and levels of antimicrobial resistance in Neisseria gonorrhoeae. J Bacteriol 191:287–297.
    869.
    Folster JP, Shafer WM. 2005. Regulation of mtrF expression in Neisseria gonorrhoeae and its role in high-level antimicrobial resistance. J Bacteriol 187:3713–3720.
    870.
    Ohneck EA, Zalucki YM, Johnson PJ, Dhulipala V, Golparian D, Unemo M, Jerse AE, Shafer WM. 2011. A novel mechanism of high-level, broad-spectrum antibiotic resistance caused by a single base pair change in Neisseria gonorrhoeae. mBio 2(5):e00187-11.
    871.
    Rouquette-Loughlin CE, Balthazar JT, Hill SA, Shafer WM. 2004. Modulation of the mtrCDE-encoded efflux pump gene complex of Neisseria meningitidis due to a Correia element insertion sequence. Mol Microbiol 54:731–741.
    872.
    Snyder LA, Cole JA, Pallen MJ. 2009. Comparative analysis of two Neisseria gonorrhoeae genome sequences reveals evidence of mobilization of Correia repeat enclosed elements and their role in regulation. BMC Genomics 10:70.
    873.
    Enriquez R, Abad R, Chanto G, Corso A, Cruces R, Gabastou JM, Gorla MC, Maldonado A, Moreno J, Muros-Le Rouzic E, Sorhouet C, Vazquez JA. 2010. Deletion of the Correia element in the mtr gene complex of Neisseria meningitidis. J Med Microbiol 59:1055–1060.
    874.
    Lin J, Akiba M, Sahin O, Zhang Q. 2005. CmeR functions as a transcriptional repressor for the multidrug efflux pump CmeABC in Campylobacter jejuni. Antimicrob Agents Chemother 49:1067–1075.
    875.
    Lin J, Cagliero C, Guo B, Barton YW, Maurel MC, Payot S, Zhang Q. 2005. Bile salts modulate expression of the CmeABC multidrug efflux pump in Campylobacter jejuni. J Bacteriol 187:7417–7424.
    876.
    Gu R, Su CC, Shi F, Li M, McDermott G, Zhang Q, Yu EW. 2007. Crystal structure of the transcriptional regulator CmeR from Campylobacter jejuni. J Mol Biol 372:583–593.
    877.
    Lei HT, Shen Z, Surana P, Routh MD, Su CC, Zhang Q, Yu EW. 2011. Crystal structures of CmeR-bile acid complexes from Campylobacter jejuni. Protein Sci 20:712–723.
    878.
    Cagliero C, Maurel MC, Cloeckaert A, Payot S. 2007. Regulation of the expression of the CmeABC efflux pump in Campylobacter jejuni: identification of a point mutation abolishing the binding of the CmeR repressor in an in vitro-selected multidrug-resistant mutant. FEMS Microbiol Lett 267:89–94.
    879.
    Hwang S, Zhang Q, Ryu S, Jeon B. 2012. Transcriptional regulation of the CmeABC multidrug efflux pump and the KatA catalase by CosR in Campylobacter jejuni. J Bacteriol 194:6883–6891.
    880.
    Shen Z, Pu XY, Zhang Q. 2011. Salicylate functions as an efflux pump inducer and promotes the emergence of fluoroquinolone-resistant Campylobacter jejuni mutants. Appl Environ Microbiol 77:7128–7133.
    881.
    Romling U, Kjelleberg S, Normark S, Nyman L, Uhlin BE, Akerlund B. 2014. Microbial biofilm formation: a need to act. J Intern Med 276:98–110.
    882.
    Mah TF. 2012. Biofilm-specific antibiotic resistance. Future Microbiol 7:1061–1072.
    883.
    O'Toole G, Kaplan HB, Kolter R. 2000. Biofilm formation as microbial development. Annu Rev Microbiol 54:49–79.
    884.
    De Kievit TR, Parkins MD, Gillis RJ, Srikumar R, Ceri H, Poole K, Iglewski BH, Storey DG. 2001. Multidrug efflux pumps: expression patterns and contribution to antibiotic resistance in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 45:1761–1770.
    885.
    Baugh S, Ekanayaka AS, Piddock LJ, Webber MA. 2012. Loss of or inhibition of all multidrug resistance efflux pumps of Salmonella enterica serovar Typhimurium results in impaired ability to form a biofilm. J Antimicrob Chemother 67:2409–2417.
    886.
    Baugh S, Phillips CR, Ekanayaka AS, Piddock LJ, Webber MA. 2014. Inhibition of multidrug efflux as a strategy to prevent biofilm formation. J Antimicrob Chemother 69:673–681.
    887.
    Tabak M, Scher K, Hartog E, Romling U, Matthews KR, Chikindas ML, Yaron S. 2007. Effect of triclosan on Salmonella typhimurium at different growth stages and in biofilms. FEMS Microbiol Lett 267:200–206.
    888.
    Matsumura K, Furukawa S, Ogihara H, Morinaga Y. 2011. Roles of multidrug efflux pumps on the biofilm formation of Escherichia coli K-12. Biocontrol Sci 16:69–72.
    889.
    Kvist M, Hancock V, Klemm P. 2008. Inactivation of efflux pumps abolishes bacterial biofilm formation. Appl Environ Microbiol 74:7376–7382.
    890.
    Liu Y, Yang L, Molin S. 2010. Synergistic activities of an efflux pump inhibitor and iron chelators against Pseudomonas aeruginosa growth and biofilm formation. Antimicrob Agents Chemother 54:3960–3963.
    891.
    Imuta N, Nishi J, Tokuda K, Fujiyama R, Manago K, Iwashita M, Sarantuya J, Kawano Y. 2008. The Escherichia coli efflux pump TolC promotes aggregation of enteroaggregative E. coli 042. Infect Immun 76:1247–1256.
    892.
    Norman A, Hansen LH, She Q, Sorensen SJ. 2008. Nucleotide sequence of pOLA52: a conjugative IncX1 plasmid from Escherichia coli which enables biofilm formation and multidrug efflux. Plasmid 60:59–74.
    893.
    Tettmann B, Dotsch A, Armant O, Fjell CD, Overhage J. 2014. Knock-out of extracytoplasmic function sigma factor ECF-10 affects stress resistance and biofilm formation in Pseudomonas putida KT2440. Appl Environ Microbiol 80:4911–4919.
    894.
    Cabral MP, Soares NC, Aranda J, Parreira JR, Rumbo C, Poza M, Valle J, Calamia V, Lasa I, Bou G. 2011. Proteomic and functional analyses reveal a unique lifestyle for Acinetobacter baumannii biofilms and a key role for histidine metabolism. J Proteome Res 10:3399–3417.
    895.
    Hoffman LR, D'Argenio DA, MacCoss MJ, Zhang Z, Jones RA, Miller SI. 2005. Aminoglycoside antibiotics induce bacterial biofilm formation. Nature 436:1171–1175.
    896.
    Heldwein EE, Brennan RG. 2001. Crystal structure of the transcription activator BmrR bound to DNA and a drug. Nature 409:378–382.
    897.
    Zhang L, Mah TF. 2008. Involvement of a novel efflux system in biofilm-specific resistance to antibiotics. J Bacteriol 190:4447–4452.
    898.
    Lynch SV, Dixon L, Benoit MR, Brodie EL, Keyhan M, Hu P, Ackerley DF, Andersen GL, Matin A. 2007. Role of the rapA gene in controlling antibiotic resistance of Escherichia coli biofilms. Antimicrob Agents Chemother 51:3650–3658.
    899.
    Pumbwe L, Skilbeck CA, Nakano V, Avila-Campos MJ, Piazza RM, Wexler HM. 2007. Bile salts enhance bacterial co-aggregation, bacterial-intestinal epithelial cell adhesion, biofilm formation and antimicrobial resistance of Bacteroides fragilis. Microb Pathog 43:78–87.
    900.
    Martínez JL, Sánchez MB, Martínez-Solano L, Hernández A, Garmendia L, Fajardo A, Alvarez-Ortega C. 2009. Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems. FEMS Microbiol Rev 33:430–449.
    901.
    Helling RB, Janes BK, Kimball H, Tran T, Bundesmann M, Check P, Phelan D, Miller C. 2002. Toxic waste disposal in Escherichia coli. J Bacteriol 184:3699–3703.
    902.
    Rosner JL, Martin RG. 2009. An excretory function for the Escherichia coli outer membrane pore TolC: upregulation of marA and soxS transcription and Rob activity due to metabolites accumulated in tolC mutants. J Bacteriol 191:5283–5292.
    903.
    Ma D, Cook DN, Alberti M, Pon NG, Nikaido H, Hearst JE. 1995. Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli. Mol Microbiol 16:45–55.
    904.
    Prouty AM, Brodsky IE, Falkow S, Gunn JS. 2004. Bile-salt-mediated induction of antimicrobial and bile resistance in Salmonella Typhimurium. Microbiology 150:775–783.
    905.
    Paul S, Alegre KO, Holdsworth SR, Rice M, Brown JA, McVeigh P, Kelly SM, Law CJ. 2014. A single-component multidrug transporter of the major facilitator superfamily is part of a network that protects Escherichia coli from bile salt stress. Mol Microbiol 92:872–884.
    906.
    Guelfo JR, Rodríguez-Rojas A, Matic I, Blazquez J. 2010. A MATE-family efflux pump rescues the Escherichia coli 8-oxoguanine-repair-deficient mutator phenotype and protects against H2O2 killing. PLoS Genet 6:e1000931.
    907.
    Bogomolnaya LM, Andrews KD, Talamantes M, Maple A, Ragoza Y, Vazquez-Torres A, Andrews-Polymenis H. 2013. The ABC-type efflux pump MacAB protects Salmonella enterica serovar Typhimurium from oxidative stress. mBio 4(6):e00630-13.
    908.
    Viveiros M, Dupont M, Rodrigues L, Couto I, Davin-Regli A, Martins M, Pagès JM, Amaral L. 2007. Antibiotic stress, genetic response and altered permeability of E. coli. PLoS One 2:e365.
    909.
    Otto K, Silhavy TJ. 2002. Surface sensing and adhesion of Escherichia coli controlled by the Cpx-signaling pathway. Proc Natl Acad Sci U S A 99:2287–2292.
    910.
    Nishino K, Yamasaki S, Hayashi-Nishino M, Yamaguchi A. 2010. Effect of NlpE overproduction on multidrug resistance in Escherichia coli. Antimicrob Agents Chemother 54:2239–2243.
    911.
    Morita Y, Sobel ML, Poole K. 2006. Antibiotic inducibility of the MexXY multidrug efflux system of Pseudomonas aeruginosa: involvement of the antibiotic-inducible PA5471 gene product. J Bacteriol 188:1847–1855.
    912.
    Godoy P, Molina-Henares AJ, de la Torre J, Duque E, Ramos JL. 2010. Characterization of the RND family of multidrug efflux pumps: in silico to in vivo confirmation of four functionally distinct subgroups. Microb Biotechnol 3:691–700.
    913.
    Jassem AN, Forbes CM, Speert DP. 2014. Investigation of aminoglycoside resistance inducing conditions and a putative AmrAB-OprM efflux system in Burkholderia vietnamiensis. Ann Clin Microbiol Antimicrob 13:2.
    914.
    Hwang S, Kim M, Ryu S, Jeon B. 2011. Regulation of oxidative stress response by CosR, an essential response regulator in Campylobacter jejuni. PLoS One 6:e22300.
    915.
    Buckley AM, Webber MA, Cooles S, Randall LP, La Ragione RM, Woodward MJ, Piddock LJ. 2006. The AcrAB-TolC efflux system of Salmonella enterica serovar Typhimurium plays a role in pathogenesis. Cell Microbiol 8:847–856.
    916.
    Yamanaka H, Kobayashi H, Takahashi E, Okamoto K. 2008. MacAB is involved in the secretion of Escherichia coli heat-stable enterotoxin II. J Bacteriol 190:7693–7698.
    917.
    Bina JE, Mekalanos JJ. 2001. Vibrio cholerae tolC is required for bile resistance and colonization. Infect Immun 69:4681–4685.
    918.
    Lin J, Martínez AL. 2006. Effect of efflux pump inhibitors on bile resistance and in vivo colonization of Campylobacter jejuni. J Antimicrob Chemother 58:966–972.
    919.
    Linkevicius M, Sandegren L, Andersson DI. 2013. Mechanisms and fitness costs of tigecycline resistance in Escherichia coli. J Antimicrob Chemother 68:2809–2819.
    920.
    Li L, Yang YR, Liao XP, Lei CY, Sun J, Li LL, Liu BT, Yang SS, Liu YH. 2013. Development of ceftriaxone resistance affects the virulence properties of Salmonella enterica serotype Typhimurium strains. Foodborne Pathog Dis 10:28–34.
    921.
    Salunkhe P, Smart CH, Morgan JA, Panagea S, Walshaw MJ, Hart CA, Geffers R, Tummler B, Winstanley C. 2005. A cystic fibrosis epidemic strain of Pseudomonas aeruginosa displays enhanced virulence and antimicrobial resistance. J Bacteriol 187:4908–4920.
    922.
    Sánchez P, Linares JF, Ruiz-Diez B, Campanario E, Navas A, Baquero F, Martínez JL. 2002. Fitness of in vitro selected Pseudomonas aeruginosa nalB and nfxB multidrug resistant mutants. J Antimicrob Chemother 50:657–664.
    923.
    Abdelraouf K, Kabbara S, Ledesma KR, Poole K, Tam VH. 2011. Effect of multidrug resistance-conferring mutations on the fitness and virulence of Pseudomonas aeruginosa. J Antimicrob Chemother 66:1311–1317.
    924.
    Mahajan-Miklos S, Rahme LG, Ausubel FM. 2000. Elucidating the molecular mechanisms of bacterial virulence using non-mammalian hosts. Mol Microbiol 37:981–988.
    925.
    Hirakata Y, Srikumar R, Poole K, Gotoh N, Suematsu T, Kohno S, Kamihira S, Hancock RE, Speert DP. 2002. Multidrug efflux systems play an important role in the invasiveness of Pseudomonas aeruginosa. J Exp Med 196:109–118.
    926.
    Hirakata Y, Kondo A, Hoshino K, Yano H, Arai K, Hirotani A, Kunishima H, Yamamoto N, Hatta M, Kitagawa M, Kohno S, Kaku M. 2009. Efflux pump inhibitors reduce the invasiveness of Pseudomonas aeruginosa. Int J Antimicrob Agents 34:343–346.
    927.
    Vettoretti L, Plésiat P, Muller C, El Garch F, Phan G, Attree I, Ducruix A, Llanes C. 2009. Efflux unbalance in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Antimicrob Agents Chemother 53:1987–1997.
    928.
    Hauser AR, Jain M, Bar-Meir M, McColley SA. 2011. Clinical significance of microbial infection and adaptation in cystic fibrosis. Clin Microbiol Rev 24:29–70.
    929.
    Cosson P, Zulianello L, Join-Lambert O, Faurisson F, Gebbie L, Benghezal M, Van Delden C, Curty LK, Köhler T. 2002. Pseudomonas aeruginosa virulence analyzed in a Dictyostelium discoideum host system. J Bacteriol 184:3027–3033.
    930.
    Linares JF, Lopez JA, Camafeita E, Albar JP, Rojo F, Martínez JL. 2005. Overexpression of the multidrug efflux pumps MexCD-OprJ and MexEF-OprN is associated with a reduction of type III secretion in Pseudomonas aeruginosa. J Bacteriol 187:1384–1391.
    931.
    Morero NR, Monti MR, Argarana CE. 2011. Effect of ciprofloxacin concentration on the frequency and nature of resistant mutants selected from Pseudomonas aeruginosa mutS and mutT hypermutators. Antimicrob Agents Chemother 55:3668–3676.
    932.
    Macia MD, Pérez JL, Molin S, Oliver A. 2011. Dynamics of mutator and antibiotic-resistant populations in a pharmacokinetic/pharmacodynamic model of Pseudomonas aeruginosa biofilm treatment. Antimicrob Agents Chemother 55:5230–5237.
    933.
    Griffith DC, Corcoran E, Lofland D, Lee A, Cho D, Lomovskaya O, Dudley MN. 2006. Pharmacodynamics of levofloxacin against Pseudomonas aeruginosa with reduced susceptibility due to different efflux pumps: do elevated MICs always predict reduced in vivo efficacy? Antimicrob Agents Chemother 50:1628–1632.
    934.
    Martínez-Ramos I, Mulet X, Moya B, Barbier M, Oliver A, Alberti S. 2014. Overexpression of MexCD-OprJ reduces Pseudomonas aeruginosa virulence by increasing its susceptibility to complement-mediated killing. Antimicrob Agents Chemother 58:2426–2429.
    935.
    Olivares J, Alvarez-Ortega C, Linares JF, Rojo F, Köhler T, Martínez JL. 2012. Overproduction of the multidrug efflux pump MexEF-OprN does not impair Pseudomonas aeruginosa fitness in competition tests, but produces specific changes in bacterial regulatory networks. Environ Microbiol 14:1968–1981.
    936.
    Köhler T, van Delden C, Curty LK, Hamzehpour MM, Pechère JC. 2001. Overexpression of the MexEF-OprN multidrug efflux system affects cell-to-cell signaling in Pseudomonas aeruginosa. J Bacteriol 183:5213–5222.
    937.
    Lamarche MG, Deziel E. 2011. MexEF-OprN efflux pump exports the Pseudomonas quinolone signal (PQS) precursor HHQ (4-hydroxy-2-heptylquinoline). PLoS One 6:e24310.
    938.
    Nicastro GG, Kaihami GH, Pereira TO, Meireles DA, Groleau MC, Deziel E, Baldini RL. 2014. Cyclic-di-GMP levels affect Pseudomonas aeruginosa fitness in the presence of imipenem. Environ Microbiol 16:1321–1333.
    939.
    Wang N, Ozer EA, Mandel MJ, Hauser AR. 2014. Genome-wide identification of Acinetobacter baumannii genes necessary for persistence in the lung. mBio 5(3):e01163-14.
    940.
    Lister IM, Mecsas J, Levy SB. 2010. Effect of MarA-like proteins on antibiotic resistance and virulence in Yersinia pestis. Infect Immun 78:364–371.
    941.
    Crimmins GT, Mohammadi S, Green ER, Bergman MA, Isberg RR, Mecsas J. 2012. Identification of MrtAB, an ABC transporter specifically required for Yersinia pseudotuberculosis to colonize the mesenteric lymph nodes. PLoS Pathog 8:e1002828.
    942.
    Kirkpatrick CL, Viollier PH. 2014. Synthetic interaction between the TipN polarity factor and an AcrAB-family efflux pump implicates cell polarity in bacterial drug resistance. Chem Biol 21:657–665.
    943.
    Silver LL. 2011. Challenges of antibacterial discovery. Clin Microbiol Rev 24:71–109.
    944.
    Pucci MJ, Bush K. 2013. Investigational antimicrobial agents of 2013. Clin Microbiol Rev 26:792–821.
    945.
    Cohen BE. 2014. Functional linkage between genes that regulate osmotic stress responses and multidrug resistance transporters: challenges and opportunities for antibiotic discovery. Antimicrob Agents Chemother 58:640–646.
    946.
    Boucher HW, Talbot GH, Benjamin DK, Jr, Bradley J, Guidos RJ, Jones RN, Murray BE, Bonomo RA, Gilbert D, Infectious Diseases Society of America. 2013. 10 × ′20 progress—development of new drugs active against Gram-negative bacilli: an update from the Infectious Diseases Society of America. Clin Infect Dis 56:1685–1694.
    947.
    Tamma PD, Cosgrove SE, Maragakis LL. 2012. Combination therapy for treatment of infections with Gram-negative bacteria. Clin Microbiol Rev 25:450–470.
    948.
    Piddock LJ. 2012. The crisis of no new antibiotics—what is the way forward? Lancet Infect Dis 12:249–253.
    949.
    Butler MS, Blaskovich MA, Cooper MA. 2013. Antibiotics in the clinical pipeline in 2013. J Antibiot (Tokyo) 66:571–591.
    950.
    Macone AB, Caruso BK, Leahy RG, Donatelli J, Weir S, Draper MP, Tanaka SK, Levy SB. 2014. In vitro and in vivo antibacterial activities of omadacycline, a novel aminomethylcycline. Antimicrob Agents Chemother 58:1127–1135.
    951.
    Draper MP, Weir S, Macone A, Donatelli J, Trieber CA, Tanaka SK, Levy SB. 2014. Mechanism of action of the novel aminomethylcycline antibiotic omadacycline. Antimicrob Agents Chemother 58:1279–1283.
    952.
    Sutcliffe JA, O'Brien W, Fyfe C, Grossman TH. 2013. Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens. Antimicrob Agents Chemother 57:5548–5558.
    953.
    Landman D, Kelly P, Backer M, Babu E, Shah N, Bratu S, Quale J. 2011. Antimicrobial activity of a novel aminoglycoside, ACHN-490, against Acinetobacter baumannii and Pseudomonas aeruginosa from New York City. J Antimicrob Chemother 66:332–334.
    954.
    Walkty A, Adam H, Baxter M, Denisuik A, Lagace-Wiens P, Karlowsky JA, Hoban DJ, Zhanel GG. 2014. In vitro activity of plazomicin against 5,015 Gram-negative and Gram-positive clinical isolates obtained from patients in Canadian hospitals as part of the CANWARD study, 2011-2012. Antimicrob Agents Chemother 58:2554–2563.
    955.
    Aggen JB, Armstrong ES, Goldblum AA, Dozzo P, Linsell MS, Gliedt MJ, Hildebrandt DJ, Feeney LA, Kubo A, Matias RD, Lopez S, Gomez M, Wlasichuk KB, Diokno R, Miller GH, Moser HE. 2010. Synthesis and spectrum of the neoglycoside ACHN-490. Antimicrob Agents Chemother 54:4636–4642.
    956.
    Mushtaq S, Warner M, Livermore DM. 2010. In vitro activity of ceftazidime+NXL104 against Pseudomonas aeruginosa and other non-fermenters. J Antimicrob Chemother 65:2376–2381.
    957.
    Clark C, McGhee P, Appelbaum PC, Kosowska-Shick K. 2011. Multistep resistance development studies of ceftaroline in Gram-positive and -negative bacteria. Antimicrob Agents Chemother 55:2344–2351.
    958.
    Bulik CC, Christensen H, Nicolau DP. 2010. In vitro potency of CXA-101, a novel cephalosporin, against Pseudomonas aeruginosa displaying various resistance phenotypes, including multidrug resistance. Antimicrob Agents Chemother 54:557–559.
    959.
    Cabot G, Bruchmann S, Mulet X, Zamorano L, Moya B, Juan C, Haussler S, Oliver A. 2014. Pseudomonas aeruginosa ceftolozane-tazobactam resistance development requires multiple mutations leading to overexpression and structural modification of AmpC. Antimicrob Agents Chemother 58:3091–3099.
    960.
    Sader HS, Castanheira M, Flamm RK, Farrell DJ, Jones RN. 2014. Antimicrobial activity of ceftazidime-avibactam against Gram-negative organisms collected from U.S. medical centers in 2012. Antimicrob Agents Chemother 58:1684–1692.
    961.
    Karlowsky JA, Adam HJ, Baxter MR, Lagace-Wiens PR, Walkty AJ, Hoban DJ, Zhanel GG. 2013. In vitro activity of ceftaroline-avibactam against Gram-negative and Gram-positive pathogens isolated from patients in Canadian hospitals from 2010 to 2012: results from the CANWARD surveillance study. Antimicrob Agents Chemother 57:5600–5611.
    962.
    Sader HS, Farrell DJ, Castanheira M, Flamm RK, Jones RN. 2014. Antimicrobial activity of ceftolozane/tazobactam tested against Pseudomonas aeruginosa and Enterobacteriaceae with various resistance patterns isolated in European hospitals (2011-12). J Antimicrob Chemother 69:2713–2722.
    963.
    Caughlan RE, Jones AK, Delucia AM, Woods AL, Xie L, Ma B, Barnes SW, Walker JR, Sprague ER, Yang X, Dean CR. 2012. Mechanisms decreasing in vitro susceptibility to the LpxC inhibitor CHIR-090 in the Gram-negative pathogen Pseudomonas aeruginosa. Antimicrob Agents Chemother 56:17–27.
    964.
    Almer LS, Hoffrage JB, Keller EL, Flamm RK, Shortridge VD. 2004. In vitro and bactericidal activities of ABT-492, a novel fluoroquinolone, against Gram-positive and Gram-negative organisms. Antimicrob Agents Chemother 48:2771–2777.
    965.
    Adam HJ, Laing NM, King CR, Lulashnyk B, Hoban DJ, Zhanel GG. 2009. In vitro activity of nemonoxacin, a novel nonfluorinated quinolone, against 2,440 clinical isolates. Antimicrob Agents Chemother 53:4915–4920.
    966.
    Higgins PG, Stubbings W, Wisplinghoff H, Seifert H. 2010. Activity of the investigational fluoroquinolone finafloxacin against ciprofloxacin-sensitive and -resistant Acinetobacter baumannii isolates. Antimicrob Agents Chemother 54:1613–1615.
    967.
    Morrow BJ, He W, Amsler KM, Foleno BD, Macielag MJ, Lynch AS, Bush K. 2010. In vitro antibacterial activities of JNJ-Q2, a new broad-spectrum fluoroquinolone. Antimicrob Agents Chemother 54:1955–1964.
    968.
    Pucci MJ, Podos SD, Thanassi JA, Leggio MJ, Bradbury BJ, Deshpande M. 2011. In vitro and in vivo profiles of ACH-702, an isothiazoloquinolone, against bacterial pathogens. Antimicrob Agents Chemother 55:2860–2871.
    969.
    Higuchi S, Onodera Y, Chiba M, Hoshino K, Gotoh N. 2013. Potent in vitro antibacterial activity of DS-8587, a novel broad-spectrum quinolone, against Acinetobacter baumannii. Antimicrob Agents Chemother 57:1978–1981.
    970.
    Higuchi S, Kurosaka Y, Uoyama S, Yoshida K, Chiba M, Ishii C, Fujikawa K, Karibe Y, Hoshino K. 2014. Anti-multidrug-resistant Acinetobacter baumannii activity of DS-8587: in vitro activity and in vivo efficacy in a murine calf muscle infection model. J Infect Chemother 20:312–316.
    971.
    Bohnert JA, Schuster S, Fahnrich E, Trittler R, Kern WV. 2007. Altered spectrum of multidrug resistance associated with a single point mutation in the Escherichia coli RND-type MDR efflux pump YhiV (MdtF). J Antimicrob Chemother 59:1216–1222.
    972.
    Kaul M, Zhang Y, Parhi AK, Lavoie EJ, Pilch DS. 2014. Inhibition of RND-type efflux pumps confers the FtsZ-directed prodrug TXY436 with activity against Gram-negative bacteria. Biochem Pharmacol 89:321–328.
    973.
    Neyfakh AA, Bidnenko VE, Chen LB. 1991. Efflux-mediated multidrug resistance in Bacillus subtilis: similarities and dissimilarities with the mammalian system. Proc Natl Acad Sci U S A 88:4781–4785.
    974.
    Matsumoto Y, Hayama K, Sakakihara S, Nishino K, Noji H, Iino R, Yamaguchi A. 2011. Evaluation of multidrug efflux pump inhibitors by a new method using microfluidic channels. PLoS One 6:e18547.
    975.
    Lamers RP, Cavallari JF, Burrows LL. 2013. The efflux inhibitor phenylalanine-arginine β-naphthylamide (PAβN) permeabilizes the outer membrane of Gram-negative bacteria. PLoS One 8:e60666.
    976.
    Paixao L, Rodrigues L, Couto I, Martins M, Fernandes P, de Carvalho CC, Monteiro GA, Sansonetty F, Amaral L, Viveiros M. 2009. Fluorometric determination of ethidium bromide efflux kinetics in Escherichia coli. J Biol Eng 3:18.
    977.
    Watkins WJ, Landaverry Y, Leger R, Litman R, Renau TE, Williams N, Yen R, Zhang JZ, Chamberland S, Madsen D, Griffith D, Tembe V, Huie K, Dudley MN. 2003. The relationship between physicochemical properties, in vitro activity and pharmacokinetic profiles of analogues of diamine-containing efflux pump inhibitors. Bioorg Med Chem Lett 13:4241–4244.
    978.
    Lomovskaya O, Bostian KA. 2006. Practical applications and feasibility of efflux pump inhibitors in the clinic—a vision for applied use. Biochem Pharmacol 71:910–918.
    979.
    Bohnert JA, Kern WV. 2005. Selected arylpiperazines are capable of reversing multidrug resistance in Escherichia coli overexpressing RND efflux pumps. Antimicrob Agents Chemother 49:849–852.
    980.
    Kern WV, Steinke P, Schumacher A, Schuster S, von Baum H, Bohnert JA. 2006. Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of Escherichia coli. J Antimicrob Chemother 57:339–343.
    981.
    Zechini B, Versace I. 2009. Inhibitors of multidrug resistant efflux systems in bacteria. Recent Pat Antiinfect Drug Discov 4:37–50.
    982.
    Schuster S, Köhler S, Buck A, Dambacher C, Konig A, Bohnert JA, Kern WV. 2014. Random mutagenesis of the multidrug transporter AcrB from Escherichia coli for identification of putative target residues of efflux pump inhibitors. Antimicrob Agents Chemother 58:6870–6878.
    983.
    Yoshida K, Nakayama K, Ohtsuka M, Kuru N, Yokomizo Y, Sakamoto A, Takemura M, Hoshino K, Kanda H, Nitanai H, Namba K, Yoshida K, Imamura Y, Zhang JZ, Lee VJ, Watkins WJ. 2007. MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 7: highly soluble and in vivo active quaternary ammonium analogue D13-9001, a potential preclinical candidate. Bioorg Med Chem 15:7087–7097.
    984.
    Eren E, Vijayaraghavan J, Liu J, Cheneke BR, Touw DS, Lepore BW, Indic M, Movileanu L, van den Berg B. 2012. Substrate specificity within a family of outer membrane carboxylate channels. PLoS Biol 10:e1001242.
    985.
    Mahamoud A, Chevalier J, Alibert-Franco S, Kern WV, Pagès J-M. 2007. Antibiotic efflux pumps in Gram-negative bacteria: the inhibitor response strategy. J Antimicrob Chemother 59:1223–1229.
    986.
    Pagès JM, Amaral L, Fanning S. 2011. An original deal for new molecule: reversal of efflux pump activity, a rational strategy to combat Gram-negative resistant bacteria. Curr Med Chem 18:2969–2980.
    987.
    Bhardwaj AK, Mohanty P. 2012. Bacterial efflux pumps involved in multidrug resistance and their inhibitors: rejuvinating the antimicrobial chemotherapy. Recent Pat Antiinfect Drug Discov 7:73–89.
    988.
    Pagès JM, Masi M, Barbe J. 2005. Inhibitors of efflux pumps in Gram-negative bacteria. Trends Mol Med 11:382–389.
    989.
    Chevalier J, Bredin J, Mahamoud A, Mallea M, Barbe J, Pagès JM. 2004. Inhibitors of antibiotic efflux in resistant Enterobacter aerogenes and Klebsiella pneumoniae strains. Antimicrob Agents Chemother 48:1043–1046.
    990.
    Thorarensen A, Presley-Bodnar AL, Marotti KR, Boyle TP, Heckaman CL, Bohanon MJ, Tomich PK, Zurenko GE, Sweeney MT, Yagi BH. 2001. 3-Arylpiperidines as potentiators of existing antibacterial agents. Bioorg Med Chem Lett 11:1903–1906.
    991.
    Bohnert JA, Schuster S, Kern WV. 2013. Pimozide inhibits the AcrAB-TolC efflux pump in Escherichia coli. Open Microbiol J 7:83–86.
    992.
    Bohnert JA, Szymaniak-Vits M, Schuster S, Kern WV. 2011. Efflux inhibition by selective serotonin reuptake inhibitors in Escherichia coli. J Antimicrob Chemother 66:2057–2060.
    993.
    Molnar J, Hever A, Fakla I, Fischer J, Ocsovski I, Aszalos A. 1997. Inhibition of the transport function of membrane proteins by some substituted phenothiazines in E. coli and multidrug resistant tumor cells. Anticancer Res 17:481–486.
    994.
    Kaatz GW, Moudgal VV, Seo SM, Kristiansen JE. 2003. Phenothiazines and thioxanthenes inhibit multidrug efflux pump activity in Staphylococcus aureus. Antimicrob Agents Chemother 47:719–726.
    995.
    Viveiros M, Martins A, Paixao L, Rodrigues L, Martins M, Couto I, Fahnrich E, Kern WV, Amaral L. 2008. Demonstration of intrinsic efflux activity of Escherichia coli K-12 AG100 by an automated ethidium bromide method. Int J Antimicrob Agents 31:458–462.
    996.
    Martins A, Machado L, Costa S, Cerca P, Spengler G, Viveiros M, Amaral L. 2011. Role of calcium in the efflux system of Escherichia coli. Int J Antimicrob Agents 37:410–414.
    997.
    Takacs D, Cerca P, Martins A, Riedl Z, Hajos G, Molnar J, Viveiros M, Couto I, Amaral L. 2011. Evaluation of forty new phenothiazine derivatives for activity against intrinsic efflux pump systems of reference Escherichia coli, Salmonella Enteritidis, Enterococcus faecalis and Staphylococcus aureus strains. In Vivo 25:719–724.
    998.
    Brunel JM, Lieutaud A, Lome V, Pagès JM, Bolla JM. 2013. Polyamino geranic derivatives as new chemosensitizers to combat antibiotic resistant Gram-negative bacteria. Bioorg Med Chem 21:1174–1179.
    999.
    Martins A, Spengler G, Rodrigues L, Viveiros M, Ramos J, Martins M, Couto I, Fanning S, Pagès JM, Bolla JM, Molnar J, Amaral L. 2009. pH modulation of efflux pump activity of multi-drug resistant Escherichia coli: protection during its passage and eventual colonization of the colon. PLoS One 4:e6656.
    1000.
    Stavri M, Piddock LJV, Gibbons S. 2007. Bacterial efflux pump inhibitors from natural sources. J Antimicrob Chemother 59:1247–1260.
    1001.
    Li B, Yao Q, Pan XC, Wang N, Zhang R, Li J, Ding G, Liu X, Wu C, Ran D, Zheng J, Zhou H. 2011. Artesunate enhances the antibacterial effect of β-lactam antibiotics against Escherichia coli by increasing antibiotic accumulation via inhibition of the multidrug efflux pump system AcrAB-TolC. J Antimicrob Chemother 66:769–777.
    1002.
    Touani FK, Seukep AJ, Djeussi DE, Fankam AG, Noumedem JA, Kuete V. 2014. Antibiotic-potentiation activities of four Cameroonian dietary plants against multidrug-resistant Gram-negative bacteria expressing efflux pumps. BMC Complement Altern Med 14:258.
    1003.
    Bag A, Chattopadhyay RR. 2014. Efflux-pump inhibitory activity of a gallotannin from Terminalia chebula fruit against multidrug-resistant uropathogenic Escherichia coli. Nat Prod Res 28:1280–1283.
    1004.
    Blanchard C, Barnett P, Perlmutter J, Dunman PM. 2014. Identification of Acinetobacter baumannii serum-associated antibiotic efflux pump inhibitors. Antimicrob Agents Chemother 58:6360–6370.
    1005.
    Biot FV, Valade E, Garnotel E, Chevalier J, Villard C, Thibault FM, Vidal DR, Pagès JM. 2011. Involvement of the efflux pumps in chloramphenicol selected strains of Burkholderia thailandensis: proteomic and mechanistic evidence. PLoS One 6:e16892.
    1006.
    Vidal-Aroca F, Meng A, Minz T, Page MG, Dreier J. 2009. Use of resazurin to detect mefloquine as an efflux-pump inhibitor in Pseudomonas aeruginosa and Escherichia coli. J Microbiol Methods 79:232–237.
    1007.
    Iino R, Nishino K, Noji H, Yamaguchi A, Matsumoto Y. 2012. A microfluidic device for simple and rapid evaluation of multidrug efflux pump inhibitors. Front Microbiol 3:40.
    1008.
    Ribera A, Jurado A, Ruiz J, Marco F, Del Valle O, Mensa J, Chaves J, Hernandez G, Jimenez de Anta MT, Vila J. 2002. In vitro activity of clinafloxacin in comparison with other quinolones against Stenotrophomonas maltophilia clinical isolates in the presence and absence of reserpine. Diagn Microbiol Infect Dis 42:123–128.
    1009.
    Shinabarger DL, Zurenko GE, Hesje CK, Sanfilippo CM, Morris TW, Haas W. 2011. Evaluation of the effect of bacterial efflux pumps on the antibacterial activity of the novel fluoroquinolone besifloxacin. J Chemother 23:80–86.
    1010.
    Koita K, Rao CV. 2012. Identification and analysis of the putative pentose sugar efflux transporters in Escherichia coli. PLoS One 7:e43700.
    1011.
    Han X, Dorsey-Oresto A, Malik M, Wang JY, Drlica K, Zhao X, Lu T. 2010. Escherichia coli genes that reduce the lethal effects of stress. BMC Microbiol 10:35.
    1012.
    Frawley ER, Crouch ML, Bingham-Ramos LK, Robbins HF, Wang W, Wright GD, Fang FC. 2013. Iron and citrate export by a major facilitator superfamily pump regulates metabolism and stress resistance in Salmonella Typhimurium. Proc Natl Acad Sci U S A 110:12054–12059.
    1013.
    Holdsworth SR, Law CJ. 2012. Functional and biochemical characterisation of the Escherichia coli major facilitator superfamily multidrug transporter MdtM. Biochimie 94:1334–1346.
    1014.
    Purewal AS, Jones IG, Midgley M. 1990. Cloning of the ethidium efflux gene from Escherichia coli. FEMS Microbiol Lett 56:73–76.
    1015.
    Morimyo M, Hongo E, Hama-Inaba H, Machida I. 1992. Cloning and characterization of the mvrC gene of Escherichia coli K-12 which confers resistance against methyl viologen toxicity. Nucleic Acids Res 20:3159–3165.
    1016.
    Higashi K, Ishigure H, Demizu R, Uemura T, Nishino K, Yamaguchi A, Kashiwagi K, Igarashi K. 2008. Identification of a spermidine excretion protein complex (MdtJI) in Escherichia coli. J Bacteriol 190:872–878.
    1017.
    Nandineni MR, Gowrishankar J. 2004. Evidence for an arginine exporter encoded by yggA (argO) that is regulated by the LysR-type transcriptional regulator ArgP in Escherichia coli. J Bacteriol 186:3539–3546.
    1018.
    Hansen LH, Sorensen SJ, Jorgensen HS, Jensen LB. 2005. The prevalence of the OqxAB multidrug efflux pump amongst olaquindox-resistant Escherichia coli in pigs. Microb Drug Resist 11:378–382.
    1019.
    Sorensen AH, Hansen LH, Johannesen E, Sorensen SJ. 2003. Conjugative plasmid conferring resistance to olaquindox. Antimicrob Agents Chemother 47:798–799.
    1020.
    Droge M, Puhler A, Selbitschka W. 2000. Phenotypic and molecular characterization of conjugative antibiotic resistance plasmids isolated from bacterial communities of activated sludge. Mol Gen Genet 263:471–482.
    1021.
    Tauch A, Schluter A, Bischoff N, Goesmann A, Meyer F, Puhler A. 2003. The 79,370-bp conjugative plasmid pB4 consists of an IncP-1β backbone loaded with a chromate resistance transposon, the strA-strB streptomycin resistance gene pair, the oxacillinase gene blaNPS-1, and a tripartite antibiotic efflux system of the resistance-nodulation-division family. Mol Genet Genomics 268:570–584.
    1022.
    Rose S, Desmolaize B, Jaju P, Wilhelm C, Warrass R, Douthwaite S. 2012. Multiplex PCR to identify macrolide resistance determinants in Mannheimia haemolytica and Pasteurella multocida. Antimicrob Agents Chemother 56:3664–3669.
    1023.
    Yuan J, Xu X, Guo Q, Zhao X, Ye X, Guo Y, Wang M. 2012. Prevalence of the oqxAB gene complex in Klebsiella pneumoniae and Escherichia coli clinical isolates. J Antimicrob Chemother 67:1655–1659.
    1024.
    Mesaros N, Glupczynski Y, Avrain L, Caceres NE, Tulkens PM, Van Bambeke F. 2007. A combined phenotypic and genotypic method for the detection of Mex efflux pumps in Pseudomonas aeruginosa. J Antimicrob Chemother 59:378–386.
    1025.
    Cabot G, Ocampo-Sosa AA, Tubau F, Macia MD, Rodríguez C, Moya B, Zamorano L, Suarez C, Pena C, Martínez-Martínez L, Oliver A. 2011. Overexpression of AmpC and efflux pumps in Pseudomonas aeruginosa isolates from bloodstream infections: prevalence and impact on resistance in a Spanish multicenter study. Antimicrob Agents Chemother 55:1906–1911.
    1026.
    Pérez A, Poza M, Aranda J, Latasa C, Medrano FJ, Tomás M, Romero A, Lasa I, Bou G. 2012. Effect of transcriptional activators SoxS, RobA, and RamA on expression of multidrug efflux pump AcrAB-TolC in Enterobacter cloacae. Antimicrob Agents Chemother 56:6256–6266.
    1027.
    Roy S, Datta S, Viswanathan R, Singh AK, Basu S. 2013. Tigecycline susceptibility in Klebsiella pneumoniae and Escherichia coli causing neonatal septicaemia (2007-10) and role of an efflux pump in tigecycline non-susceptibility. J Antimicrob Chemother 68:1036–1042.
    1028.
    Lewinson O, Adler J, Poelarends GJ, Mazurkiewicz P, Driessen AJ, Bibi E. 2003. The Escherichia coli multidrug transporter MdfA catalyzes both electrogenic and electroneutral transport reactions. Proc Natl Acad Sci U S A 100:1667–1672.
    1029.
    CLSI. 2014. Performance standards for antimicrobial susceptibility testing. Twenty-fourth informational supplement. M100-S24. CLSI, Wayne, PA.
    1030.
    Ghisalberti D, Mahamoud A, Chevalier J, Baitiche M, Martino M, Pagès JM, Barbe J. 2006. Chloroquinolines block antibiotic efflux pumps in antibiotic-resistant Enterobacter aerogenes isolates. Int J Antimicrob Agents 27:565–569.

    Author Bios

    Human Safety Division, Veterinary Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada
    Xian-Zhi Li received his medical degree and an M.Sc. in Pharmacology from Luzhou Medical College and West China University of Medical Sciences, respectively, in China in the 1980s. He later obtained another M.Sc. and a Ph.D. in Microbiology from the University of Saskatchewan and Queen's University (Kingston) in Canada, respectively. He is currently a team leader at Health Canada and is involved in microbiological and toxicological assessments of premarket drugs as well as antimicrobial drug policy development. He is also an advisor to the Veterinary Antimicrobial Susceptibility Testing Subcommittee of the Clinical and Laboratory Standards Institute. He has published over 70 peer-reviewed articles on antimicrobial resistance with notable contributions to the seminal discovery and characterization of RND pumps of Pseudomonas and Stenotrophomonas at the University of California, Berkeley, and Queen's University. His interests include antimicrobial resistance evolution, mechanisms, and risk assessment.
    Patrick Plésiat
    Laboratoire de Bactériologie, Faculté de Médecine-Pharmacie, Centre Hospitalier Régional Universitaire, Université de Franche-Comté, Besançon, France
    Patrick Plésiat received his Pharm.D. and Ph.D. from Franche-Comté University, France. After a postdoctoral year at the University of California, Berkeley, in 1990 to 1991 with Hiroshi Nikaido, he was appointed head of the Bacteriology Department at University Hospital Jean Minjoz, Besançon, France, in 1995 and became professor at the Faculty of Medicine in the same city in 1997. In 2012, he was appointed by the French Ministry of Health as coordinator of the National Reference Center for Antibiotic Resistance. Since the early 1990s, his main research interests have been the porin- and efflux-based mechanisms leading to multidrug resistance in clinical strains of Pseudomonas aeruginosa, with special interest for the MexXY/OprM (OprA) pump. He has published more than 120 peer-reviewed papers. His current research is on the regulation of efflux systems and lipopolysaccharide modifications.
    Hiroshi Nikaido [email protected]
    Department of Molecular and Cell Biology, University of California, Berkeley, California, USA
    Hiroshi Nikaido received his M.D. and Ph.D. from Keio University in Tokyo, Japan. After a postdoctoral year with Herman Kalckar, he became a faculty member in the Bacteriology Department of Harvard Medical School in 1963. He moved to the University of California, Berkeley, in 1969, first as an Associate Professor of Bacteriology, and is now an emeritus Professor in the Department of Molecular and Cell Biology. At Harvard Medical School, his interest was in the biosynthesis of lipopolysaccharides. In the 1980s, he became interested in the property of the bacterial outer membrane as a permeability barrier, a topic that led to the discovery of bacterial porins. Since the mid-1990s, his main interest has been the multidrug efflux pumps of bacteria, especially AcrB of Escherichia coli. He has published more than 300 peer-reviewed papers, and he is a Fellow of the American Academy of Arts and Science and a member of the National Academy of Sciences.

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    Clinical Microbiology Reviews
    Volume 28Number 2April 2015
    Pages: 337 - 418

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    Published online: 18 March 2015

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    Human Safety Division, Veterinary Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada
    Patrick Plésiat
    Laboratoire de Bactériologie, Faculté de Médecine-Pharmacie, Centre Hospitalier Régional Universitaire, Université de Franche-Comté, Besançon, France
    Hiroshi Nikaido [email protected]
    Department of Molecular and Cell Biology, University of California, Berkeley, California, USA

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  • Clinical Microbiology ReviewsArticle
    Antifungal Susceptibility Testing: Current Approaches

    Antifungal Susceptibility Testing: Current Approaches

    SUMMARY

    Although not as ubiquitous as antibacterial susceptibility testing, antifungal susceptibility testing (AFST) is a tool of increasing importance in clinical microbiology laboratories. The goal of AFST is to reliably produce MIC values that may be used to guide patient therapy, inform epidemiological studies, and track rates of antifungal drug resistance. There are three methods that have been standardized by standards development organizations: broth dilution, disk diffusion, and azole agar screening for Aspergillus. Other commonly used methods include gradient diffusion and the use of rapid automated instruments. Novel methodologies for susceptibility testing are in development. It is important for laboratories to consider not only the method of testing but also the interpretation (or lack thereof) of in vitro data.

    REFERENCES

    1.
    Rex JH, Pfaller MA, Galgiani JN, Bartlett MS, Espinel-Ingroff A, Ghannoum MA, Lancaster M, Odds FC, Rinaldi MG, Walsh TJ, Barry AL. 1997. Development of interpretive breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro-in vivo correlation data for fluconazole, itraconazole, and candida infections. Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards. Clin Infect Dis 24:235–247.
    2.
    Calhoun DL, Roberts GD, Galgiani JN, Bennett JE, Feingold DS, Jorgensen J, Kobayashi GS, Shadomy S. 1986. Results of a survey of antifungal susceptibility tests in the United States and interlaboratory comparison of broth dilution testing of flucytosine and amphotericin B. J Clin Microbiol 23:298–301.
    3.
    Galgiani JN, Reiser J, Brass C, Espinel-Ingroff A, Gordon MA, Kerkering TM. 1987. Comparison of relative susceptibilities of Candida species to three antifungal agents as determined by unstandardized methods. Antimicrob Agents Chemother 31:1343–1347.
    4.
    National Committee for Clinical Laboratory Standards. 1997. Reference method for broth dilution antifungal susceptibility testing of yeasts. National Committee for Clinical Laboratory Standards, Wayne, PA.
    5.
    . 2008. EUCAST definitive document EDef 7.1: method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts. Clin Microbiol Infect 14:398–405.
    6.
    Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, Reboli AC, Schuster MG, Vazquez JA, Walsh TJ, Zaoutis TE, Sobel JD. 2016. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 62:e1–e50.
    7.
    Cuenca-Estrella M, Verweij PE, Arendrup MC, Arikan-Akdagli S, Bille J, Donnelly JP, Jensen HE, Lass-Florl C, Richardson MD, Akova M, Bassetti M, Calandra T, Castagnola E, Cornely OA, Garbino J, Groll AH, Herbrecht R, Hope WW, Kullberg BJ, Lortholary O, Meersseman W, Petrikkos G, Roilides E, Viscoli C, Ullmann AJ. 2012. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clin Microbiol Infect 18(Suppl 7):9–18.
    8.
    Subcommittee on Antifungal Susceptibility Tests. January 2019. Antifungal susceptibility testing meeting minutes, January 2019. https://clsi.org/meetings/sub-antifungal/antifungal-susceptibility-testing-files-resources/.
    9.
    Ullmann AJ, Aguado JM, Arikan-Akdagli S, Denning DW, Groll AH, Lagrou K, Lass-Florl C, Lewis RE, Munoz P, Verweij PE, Warris A, Ader F, Akova M, Arendrup MC, Barnes RA, Beigelman-Aubry C, Blot S, Bouza E, Bruggemann RJM, Buchheidt D, Cadranel J, Castagnola E, Chakrabarti A, Cuenca-Estrella M, Dimopoulos G, Fortun J, Gangneux JP, Garbino J, Heinz WJ, Herbrecht R, Heussel CP, Kibbler CC, Klimko N, Kullberg BJ, Lange C, Lehrnbecher T, Loffler J, Lortholary O, Maertens J, Marchetti O, Meis JF, Pagano L, Ribaud P, Richardson M, Roilides E, Ruhnke M, Sanguinetti M, Sheppard DC, Sinko J, Skiada A, et al. 2018. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect 24(Suppl 1):e1–e38.
    10.
    Arendrup MC, Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST), Meletiadis J, Mouton JW, Guinea J, Cuenca-Estrella M, Lagrou K, Howard SJ. 2016. EUCAST technical note on isavuconazole breakpoints for Aspergillus, itraconazole breakpoints for Candida and updates for the antifungal susceptibility testing method documents. Clin Microbiol Infect 22:571.e1–e4.
    11.
    Hope WW, Cuenca-Estrella M, Lass-Flörl C, Arendrup MC, European Committee on Antimicrobial Susceptibility Testing-Subcommittee on Antifungal Susceptibility Testing. 2013. EUCAST technical note on voriconazole and Aspergillus spp. Clin Microbiol Infect 19:E278–E80.
    12.
    Arendrup MC, Cuenca-Estrella M, Lass-Flörl C, Hope WW, European Committee on Antimicrobial Susceptibility Testing Subcommittee on Antifungal Susceptibility Testing. 2012. EUCAST technical note on Aspergillus and amphotericin B, itraconazole, and posaconazole. Clin Microbiol Infect 18:E248–E250.
    13.
    Pfaller MA, Bale M, Buschelman B, Lancaster M, Espinel-Ingroff A, Rex JH, Rinaldi MG. 1994. Selection of candidate quality control isolates and tentative quality control ranges for in vitro susceptibility testing of yeast isolates by National Committee for Clinical Laboratory Standards proposed standard methods. J Clin Microbiol 32:1650–1653.
    14.
    Pfaller MA, Diekema DJ. 2007. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20:133–163.
    15.
    Lamoth F, Lockhart SR, Berkow EL, Calandra T. 2018. Changes in the epidemiological landscape of invasive candidiasis. J Antimicrob Chemother 73:i4–i13.
    16.
    Wiederhold NP. 2016. Echinocandin resistance in Candida species: a review of recent developments. Curr Infect Dis Rep 18:42.
    17.
    Goncalves SS, Souza ACR, Chowdhary A, Meis JF, Colombo AL. 2016. Epidemiology and molecular mechanisms of antifungal resistance in Candida and Aspergillus. Mycoses 59:198–219.
    18.
    Resendiz Sharpe A, ISHAM/ECMM Aspergillus Resistance Surveillance Working Group, Lagrou K, Meis JF, Chowdhary A, Lockhart SR, Verweij PE. 2018. Triazole resistance surveillance in Aspergillus fumigatus. Med Mycol 56:83–92.
    19.
    Lestrade PP, Bentvelsen RG, Schauwvlieghe A, Schalekamp S, van der Velden W, Kuiper EJ, van Paassen J, van der Hoven B, van der Lee HA, Melchers WJG, de Haan AF, van der Hoeven HL, Rijnders BJA, van der Beek MT, Verweij PE. 2019. Voriconazole resistance and mortality in invasive aspergillosis: a multicenter retrospective cohort study. Clin Infect Dis 68:1463–1471.
    20.
    Schauwvlieghe A, de Jonge N, van Dijk K, Verweij PE, Bruggemann RJ, Biemond BJ, Bart A, von Dem Borne PA, Verbon A, van der Beek MT, Demandt AMP, Oudhuis GJ, Cornelissen JJ, van der Velden W, Span LFR, Kampinga GA, Bruns AH, Vonk AG, Haas PA, Doorduijn JK, Rijnders B. 2018. The diagnosis and treatment of invasive aspergillosis in Dutch haematology units facing a rapidly increasing prevalence of azole-resistance. A nationwide survey and rationale for the DB-MSG 002 study protocol. Mycoses 61:656–664.
    21.
    Kathuria S, Singh PK, Sharma C, Prakash A, Masih A, Kumar A, Meis JF, Chowdhary A. 2015. Multidrug-resistant Candida auris misidentified as Candida haemulonii: characterization by matrix-assisted laser desorption ionization-time of flight mass spectrometry and DNA sequencing and its antifungal susceptibility profile variability by Vitek 2, CLSI broth microdilution, and Etest method. J Clin Microbiol 53:1823–1830.
    22.
    Chowdhary A, Sharma C, Meis JF. 2017. Candida auris: a rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoS Pathog 13:e1006290.
    23.
    Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, Colombo AL, Calvo B, Cuomo CA, Desjardins CA, Berkow EL, Castanheira M, Magobo RE, Jabeen K, Asghar RJ, Meis JF, Jackson B, Chiller T, Litvintseva AP. 2017. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis 64:134–140.
    24.
    Galgiant JN, Stevens DA. 1978. Turbidimetric studies of growth inhibition of yeasts with three drugs: inquiry into inoculum-dependent susceptibility testing, time of onset of drug effect, and implications for current and newer methods. Antimicrob Agents Chemother 13:249–254.
    25.
    Galgiani JN, Stevens DA. 1976. Antimicrobial susceptibility testing of yeasts: a turbidimetric technique independent of inoculum size. Antimicrob Agents Chemother 10:721–728.
    26.
    Arendrup MC, Meletiadis J, Mouton JW, Lagrou K, Hamal P, Guinea J, Subcommittee on Antifungal Susceptibility Testing of the ESCMID European Committee for Antimicrobial Susceptibility Testing. 2017. EUCAST definitive document E.DEF 7.3.1. Method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/AFST/Files/EUCAST_E_Def_7_3_1_Yeast_testing__definitive.pdf.
    27.
    Clinical and Laboratory Standards Institute. 2017. Reference method for broth dilution antifungal susceptibility testing of yeasts, 4th ed. Approved standard M27. Clinical and Laboratory Standards Institute, Wayne, PA.
    28.
    National Committee for Clinical Laboratory Standards. 1992. Reference method for broth dilution antifungal susceptibility testing of yeasts. Proposed standard M27-P. National Committee for Clinical Laboratory Standards, Villanova, PA.
    29.
    Clinical and Laboratory Standards Institute. 2017. Performance standards for antifungal susceptibility testing of yeasts, 1st ed. CLSI supplement M60. Clinical and Laboratory Standards Institute, Wayne PA.
    30.
    Arendrup MC, Kahlmeter G, Rodriguez-Tudela JL, Donnelly JP. 2009. Breakpoints for susceptibility testing should not divide wild-type distributions of important target species. Antimicrob Agents Chemother 53:1628–1629.
    31.
    Shields RK, Nguyen MH, Press EG, Updike CL, Clancy CJ. 2013. Caspofungin MICs correlate with treatment outcomes among patients with Candida glabrata invasive candidiasis and prior echinocandin exposure. Antimicrob Agents Chemother 57:3528–3535.
    32.
    Espinel-Ingroff A, Arendrup MC, Pfaller MA, Bonfietti LX, Bustamante B, Canton E, Chryssanthou E, Cuenca-Estrella M, Dannaoui E, Fothergill A, Fuller J, Gaustad P, Gonzalez GM, Guarro J, Lass-Florl C, Lockhart SR, Meis JF, Moore CB, Ostrosky-Zeichner L, Pelaez T, Pukinskas SR, St-Germain G, Szeszs MW, Turnidge J. 2013. Interlaboratory variability of caspofungin MICs for Candida spp. using CLSI and EUCAST methods: should the clinical laboratory be testing this agent? Antimicrob Agents Chemother 57:5836–5842.
    33.
    Pfaller MA, Messer SA, Diekema DJ, Jones RN, Castanheira M. 2014. Use of micafungin as a surrogate marker to predict susceptibility and resistance to caspofungin among 3,764 clinical isolates of Candida by use of CLSI methods and interpretive criteria. J Clin Microbiol 52:108–114.
    34.
    Pfaller MA, Diekema DJ, Jones RN, Castanheira M. 2014. Use of anidulafungin as a surrogate marker to predict susceptibility and resistance to caspofungin among 4,290 clinical isolates of Candida by using CLSI methods and interpretive criteria. J Clin Microbiol 52:3223–3229.
    35.
    Clinical and Laboratory Standards Institute. 2017. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi, 3rd ed. Clinical and Laboratory Standards Institute, Wayne, PA.
    36.
    Arendrup MC, Meletiadis J, Mouton JW, Lagrou K, Hamal P, Guinea J, Subcommittee on Antifungal Susceptibility Testing of the ESCMID European Committee for Antimicrobial Susceptibility Testing. 2017. Method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia forming moulds. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/AFST/Files/EUCAST_E_Def_9_3_1_Mould_testing__definitive.pdf.
    37.
    Saubolle MA, Hoeprich PD. 1978. Disk agar diffusion susceptibility testing of yeasts. Antimicrob Agents Chemother 14:517–530.
    38.
    Barry AL, Pfaller MA, Rennie RP, Fuchs PC, Brown SD. 2002. Precision and accuracy of fluconazole susceptibility testing by broth microdilution, Etest, and disk diffusion methods. Antimicrob Agents Chemother 46:1781–1784.
    39.
    Kirkpatrick WR, Turner TM, Fothergill AW, McCarthy DI, Redding SW, Rinaldi MG, Patterson TF. 1998. Fluconazole disk diffusion susceptibility testing of Candida species. J Clin Microbiol 36:3429–3432.
    40.
    Pfaller MA, Barry A, Bille J, Brown S, Ellis D, Meis JF, Rennie R, Rinaldi M, Rogers T, Traczewski M. 2004. Quality control limits for voriconazole disk susceptibility tests on Mueller-Hinton agar with glucose and methylene blue. J Clin Microbiol 42:1716–1718.
    41.
    Clinical and Laboratory Standards Institute. 2009. Method for antifungal disk diffusion susceptibility testing of yeasts; approved guideline, 2nd ed. CLSI document M44-A2. Clinical and Laboratory Standards Institute, Wayne, PA.
    42.
    Brown SD, Traczewski MM. 2008. Caspofungin disk diffusion breakpoints and quality control. J Clin Microbiol 46:1927–1929.
    43.
    Espinel-Ingroff A, Arthington-Skaggs B, Iqbal N, Ellis D, Pfaller MA, Messer S, Rinaldi M, Fothergill A, Gibbs DL, Wang A. 2007. Multicenter evaluation of a new disk agar diffusion method for susceptibility testing of filamentous fungi with voriconazole, posaconazole, itraconazole, amphotericin B, and caspofungin. J Clin Microbiol 45:1811–1820.
    44.
    Mendez CC, Serrano MC, Valverde A, Peman J, Almeida C, Martin-Mazuelos E. 2008. Comparison of E-test, disk diffusion and a modified CLSI broth microdilution (M 38-A) method for in vitro testing of itraconazole, fluconazole and voriconazole against dermatophytes. Med Mycol 46:119–123.
    45.
    Ozkutuk A, Ergon C, Metin DY, Yucesoy M, Polat SH. 2008. Comparison of disk diffusion, E-test and broth microdilution test in determination of susceptibility of Aspergillus species to amphotericin B, itraconazole and voriconazole. J Chemother 20:87–92.
    46.
    Clinical and Laboratory Standards Institute. 2010. Method for antifungal disk diffusion susceptibility testing of nondermatophyte filamentous fungi, approved guideline. CLSI document M51-A. Clinical and Laboratory Standards Institute, Wayne, PA.
    47.
    Pfaller MA, Global Antifungal Surveillance Group, Diekema DJ, Gibbs DL, Newell VA, Ellis D, Tullio V, Rodloff A, Fu W, Ling TA. 2010. Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-year analysis of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. J Clin Microbiol 48:1366–1377.
    48.
    Meis J, Petrou M, Bille J, Ellis D, Gibbs D. 2000. A global evaluation of the susceptibility of Candida species to fluconazole by disk diffusion. Global Antifungal Surveillance Group. Diagn Microbiol Infect Dis 36:215–223.
    49.
    Pfaller MA, Diekema DJ, Messer SA, Boyken L, Hollis RJ. 2003. Activities of fluconazole and voriconazole against 1,586 recent clinical isolates of Candida species determined by broth microdilution, disk diffusion, and Etest methods: report from the ARTEMIS Global Antifungal Susceptibility Program, 2001. J Clin Microbiol 41:1440–1446.
    50.
    Pfaller MA, Boyken L, Messer SA, Tendolkar S, Hollis RJ, Diekema DJ. 2005. Comparison of results of voriconazole disk diffusion testing for Candida species with results from a central reference laboratory in the ARTEMIS Global Antifungal Surveillance Program. J Clin Microbiol 43:5208–5213.
    51.
    Arendrup MC, Park S, Brown S, Pfaller M, Perlin DS. 2011. Evaluation of CLSI M44-A2 disk diffusion and associated breakpoint testing of caspofungin and micafungin using a well-characterized panel of wild-type and fks hot spot mutant Candida isolates. Antimicrob Agents Chemother 55:1891–1895.
    52.
    Pfaller MA, Messer SA, Boyken L, Rice C, Tendolkar S, Hollis RJ, Diekema DJ. 2004. Evaluation of the NCCLS M44-P disk diffusion method for determining susceptibilities of 276 clinical isolates of Cryptococcus neoformans to fluconazole. J Clin Microbiol 42:380–383.
    53.
    Pfaller MA, Hazen KC, Messer SA, Boyken L, Tendolkar S, Hollis RJ, Diekema DJ. 2004. Comparison of results of fluconazole disk diffusion testing for Candida species with results from a central reference laboratory in the ARTEMIS global antifungal surveillance program. J Clin Microbiol 42:3607–3612.
    54.
    Pfaller MA, ARTEMIS DISK Global Antifungal Surveillance Group, Boyken L, Hollis RJ, Kroeger J, Messer SA, Tendolkar S, Diekema DJ. 2009. Comparison of results of fluconazole and voriconazole disk diffusion testing for Candida spp. with results from a central reference laboratory in the ARTEMIS DISK Global Antifungal Surveillance Program. Diagn Microbiol Infect Dis 65:27–34.
    55.
    Arendrup MC, Verweij PE, Mouton JW, Lagrou K, Meletiadis J. 2018. Multicentre validation of 4-well azole agar plates as a screening method for detection of clinically relevant azole-resistant Aspergillus fumigatus. J Antimicrob Chemother 73:2274.
    56.
    Buil JB, van der Lee HAL, Rijs A, Zoll J, Hovestadt J, Melchers WJG, Verweij PE. 2017. Single-center evaluation of an agar-based screening for azole resistance in Aspergillus fumigatus by using VIPcheck. Antimicrob Agents Chemother 61:e01250-17.
    57.
    Guinea J, Verweij PE, Meletiadis J, Mouton JW, Barchiesi F, Arendrup MC, Subcommittee on Antifungal Susceptibility Testing of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST). 2019. How to: EUCAST recommendations on the screening procedure E.Def 10.1 for the detection of azole resistance in Aspergillus fumigatus isolates using four-well azole-containing agar plates. Clin Microbiol Infect 25:681–687.
    58.
    Pfaller MA, Messer SA, Houston A, Mills K, Bolmstrom A, Jones RN. 2000. Evaluation of the Etest method for determining voriconazole susceptibilities of 312 clinical isolates of Candida species by using three different agar media. J Clin Microbiol 38:3715–3717.
    59.
    Pfaller MA, Messer SA, Mills K, Bolmstrom A. 2000. In vitro susceptibility testing of filamentous fungi: comparison of Etest and reference microdilution methods for determining itraconazole MICs. J Clin Microbiol 38:3359–3361.
    60.
    Alexander BD, Byrne TC, Smith KL, Hanson KE, Anstrom KJ, Perfect JR, Reller LB. 2007. Comparative evaluation of Etest and Sensititre YeastOne panels against the Clinical and Laboratory Standards Institute M27-A2 reference broth microdilution method for testing Candida susceptibility to seven antifungal agents. J Clin Microbiol 45:698–706.
    61.
    Diekema DJ, Messer SA, Hollis RJ, Boyken LB, Tendolkar S, Kroeger J, Pfaller MA. 2007. Evaluation of Etest and disk diffusion methods compared with broth microdilution antifungal susceptibility testing of clinical isolates of Candida spp. against posaconazole. J Clin Microbiol 45:1974–1977.
    62.
    Arendrup M, Lundgren B, Jensen IM, Hansen BS, Frimodt-Møller N. 2001. Comparison of Etest and a tablet diffusion test with the NCCLS broth microdilution method for fluconazole and amphotericin B susceptibility testing of Candida isolates. J Antimicrob Chemother 47:521–526.
    63.
    Pfaller MA, Messer SA, Mills K, Bolmstrom A, Jones RN. 2001. Evaluation of Etest method for determining posaconazole MICs for 314 clinical isolates of Candida species. J Clin Microbiol 39:3952–3954.
    64.
    Pfaller MA, Messer SA, Mills K, Bolmstrom A, Jones RN. 2001. Evaluation of Etest method for determining caspofungin (MK-0991) susceptibilities of 726 clinical isolates of Candida species. J Clin Microbiol 39:4387–4389.
    65.
    Cuenca-Estrella M, Gomez-Lopez A, Mellado E, Rodriguez-Tudela JL. 2005. Correlation between the procedure for antifungal susceptibility testing for Candida spp. of the European Committee on Antibiotic Susceptibility Testing (EUCAST) and four commercial techniques. Clin Microbiol Infect 11:486–492.
    66.
    Pfaller MA, Castanheira M, Diekema DJ, Messer SA, Moet GJ, Jones RN. 2010. Comparison of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Etest methods with the CLSI broth microdilution method for echinocandin susceptibility testing of Candida species. J Clin Microbiol 48:1592–1599.
    67.
    Idelevich EA, Groß U, Becker K, Bader O. 2018. Comparative evaluation of different gradient diffusion tests for detection of azole resistance in Aspergillus fumigatus. Diagn Microbiol Infect Dis 91:52–54.
    68.
    Al-Hatmi AM, Normand AC, Ranque S, Piarroux R, de Hoog GS, Meletiadis J, Meis JF. 2017. Comparative evaluation of Etest, EUCAST, and CLSI methods for amphotericin B, voriconazole, and posaconazole against clinically relevant Fusarium species. Antimicrob Agents Chemother 61:e01671-16.
    69.
    Pfaller JB, Messer SA, Hollis RJ, Diekema DJ, Pfaller MA. 2003. In vitro susceptibility testing of Aspergillus spp.: comparison of Etest and reference microdilution methods for determining voriconazole and itraconazole MICs. J Clin Microbiol 41:1126–1129.
    70.
    Espinel-Ingroff A, Rezusta A. 2002. E-test method for testing susceptibilities of Aspergillus spp. to the new triazoles voriconazole and posaconazole and to established antifungal agents: comparison with NCCLS broth microdilution method. J Clin Microbiol 40:2101–2107.
    71.
    Serrano MC, Morilla D, Valverde A, Chávez M, Espinel-Ingroff A, Claro R, Ramírez M, Mazuelos EM. 2003. Comparison of Etest with modified broth microdilution method for testing susceptibility of Aspergillus spp. to voriconazole. J Clin Microbiol 41:5270–5272.
    72.
    Torres-Narbona M, Guinea J, Martínez-Alarcón J, Peláez T, Bouza E. 2007. In vitro activities of amphotericin B, caspofungin, itraconazole, posaconazole, and voriconazole against 45 clinical isolates of zygomycetes: comparison of CLSI M38-A, Sensititre YeastOne, and the Etest. Antimicrob Agents Chemother 51:1126–1129.
    73.
    Caramalho R, Maurer E, Binder U, Araújo R, Dolatabadi S, Lass-Flörl C, Lackner M. 2015. Etest cannot be recommended for in vitro susceptibility testing of Mucorales. Antimicrob Agents Chemother 59:3663–3665.
    74.
    Lamoth F, Alexander BD. 2015. Comparing Etest and broth microdilution for antifungal susceptibility testing of the most-relevant pathogenic molds. J Clin Microbiol 53:3176–3181.
    75.
    Law D, Moore CB, Denning DW. 1997. Amphotericin B resistance testing of Candida spp.: a comparison of methods. J Antimicrob Chemother 40:109–112.
    76.
    Pfaller MA, Messer SA, Bolmstrom A. 1998. Evaluation of Etest for determining in vitro susceptibility of yeast isolates to amphotericin B. Diagn Microbiol Infect Dis 32:223–227.
    77.
    Peyron F, Favel A, Michel-Nguyen A, Gilly M, Regli P, Bolmström A. 2001. Improved detection of amphotericin B-resistant isolates of Candida lusitaniae by Etest. J Clin Microbiol 39:339–342.
    78.
    Wanger A, Mills K, Nelson PW, Rex JH. 1995. Comparison of Etest and National Committee for Clinical Laboratory Standards broth macrodilution method for antifungal susceptibility testing: enhanced ability to detect amphotericin B-resistant Candida isolates. Antimicrob Agents Chemother 39:2520–2522.
    79.
    Lozano-Chiu M, Paetznick VL, Ghannoum MA, Rex JH. 1998. Detection of resistance to amphotericin B among Cryptococcus neoformans clinical isolates: performances of three different media assessed by using E-test and National Committee for Clinical Laboratory Standards M27-A methodologies. J Clin Microbiol 36:2817–2822.
    80.
    Espinel-Ingroff A, Pfaller M, Messer SA, Knapp CC, Killian S, Norris HA, Ghannoum MA. 1999. Multicenter comparison of the Sensititre YeastOne colorimetric antifungal panel with the National Committee for Clinical Laboratory standards M27-A reference method for testing clinical isolates of common and emerging Candida spp., Cryptococcus spp., and other yeasts and yeast-like organisms. J Clin Microbiol 37:591–595.
    81.
    Pfaller MA, Messer SA, Hollis RJ, Espinel-Ingroff A, Ghannoum MA, Plavan H, Killian SB, Knapp CC. 1998. Multisite reproducibility of MIC results by the Sensititre YeastOne colorimetric antifungal susceptibility panel. Diagn Microbiol Infect Dis 31:543–547.
    82.
    Morace G, Amato G, Bistoni F, Fadda G, Marone P, Montagna MT, Oliveri S, Polonelli L, Rigoli R, Mancuso I, La Face S, Masucci L, Romano L, Napoli C, Tatò D, Buscema MG, Belli CMC, Piccirillo MM, Conti S, Covan S, Fanti F, Cavanna C, D'Alò F, Pitzurra L. 2002. Multicenter comparative evaluation of six commercial systems and the National Committee for Clinical Laboratory Standards M27-A broth microdilution method for fluconazole susceptibility testing of Candida species. J Clin Microbiol 40:2953–2958.
    83.
    Espinel-Ingroff A, Pfaller M, Messer SA, Knapp CC, Holliday N, Killian SB. 2004. Multicenter comparison of the Sensititre YeastOne colorimetric antifungal panel with the NCCLS M27-A2 reference method for testing new antifungal agents against clinical isolates of Candida spp. J Clin Microbiol 42:718–721.
    84.
    Pfaller MA, Chaturvedi V, Diekema DJ, Ghannoum MA, Holliday NM, Killian SB, Knapp CC, Messer SA, Miskov A, Ramani R. 2008. Clinical evaluation of the Sensititre YeastOne colorimetric antifungal panel for antifungal susceptibility testing of the echinocandins anidulafungin, caspofungin, and micafungin. J Clin Microbiol 46:2155–2159.
    85.
    Pfaller MA, Chaturvedi V, Diekema DJ, Ghannoum MA, Holliday NM, Killian SB, Knapp CC, Messer SA, Miskou A, Ramani R. 2012. Comparison of the Sensititre YeastOne colorimetric antifungal panel with CLSI microdilution for antifungal susceptibility testing of the echinocandins against Candida spp., using new clinical breakpoints and epidemiological cutoff values. Diagn Microbiol Infect Dis 73:365–368.
    86.
    Martín-Mazuelos E, Pemán J, Valverde A, Chaves M, Serrano MC, Cantón E. 2003. Comparison of the Sensititre YeastOne colorimetric antifungal panel and Etest with the NCCLS M38-A method to determine the activity of amphotericin B and itraconazole against clinical isolates of Aspergillus spp. J Antimicrob Chemother 52:365–370.
    87.
    Castro C, Serrano MC, Flores B, Espinel-Ingroff A, Martín-Mazuelos E. 2004. Comparison of the Sensititre YeastOne colorimetric antifungal panel with a modified NCCLS M38-A method to determine the activity of voriconazole against clinical isolates of Aspergillus spp. J Clin Microbiol 42:4358–4360.
    88.
    Guinea J, Pelaez T, Alcala L, Bouza E. 2006. Comparison of Sensititre YeastOne with the NCCLS M38-A microdilution method to determine the activity of amphotericin B, voriconazole, and itraconazole against clinical isolates of Aspergillus fumigatus. Diagn Microbiol Infect Dis 56:53–55.
    89.
    Patel R, Mendrick C, Knapp CC, Grist R, McNicholas PM. 2007. Clinical evaluation of the Sensititre YeastOne plate for testing susceptibility of filamentous fungi to posaconazole. J Clin Microbiol 45:2000–2001.
    90.
    Alvarado-Ramirez E, Torres-Rodriguez JM. 2007. In vitro susceptibility of Sporothrix schenckii to six antifungal agents determined using three different methods. Antimicrob Agents Chemother 51:2420–2423.
    91.
    Wang HC, Hsieh MI, Choi PC, Wu CJ. 2018. Comparison of the Sensititre YeastOne and CLSI M38-A2 microdilution methods in determining the activity of amphotericin B, itraconazole, voriconazole, and posaconazole against Aspergillus species. J Clin Microbiol 56:e00780-18.
    92.
    Halliday CL, Chen SC, Kidd SE, van Hal S, Chapman B, Heath CH, Lee A, Kennedy KJ, Daveson K, Sorrell TC, Morrissey CO, Marriott DJ, Slavin MA. 2016. Antifungal susceptibilities of non-Aspergillus filamentous fungi causing invasive infection in Australia: support for current antifungal guideline recommendations. Int J Antimicrob Agents 48:453–458.
    93.
    Pfaller MA, Diekema DJ, Procop GW, Rinaldi MG. 2007. Multicenter comparison of the VITEK 2 antifungal susceptibility test with the CLSI broth microdilution reference method for testing amphotericin B, flucytosine, and voriconazole against Candida spp. J Clin Microbiol 45:3522–3528.
    94.
    Posteraro B, Martucci R, La Sorda M, Fiori B, Sanglard D, De Carolis E, Florio AR, Fadda G, Sanguinetti M. 2009. Reliability of the Vitek 2 yeast susceptibility test for detection of in vitro resistance to fluconazole and voriconazole in clinical isolates of Candida albicans and Candida glabrata. J Clin Microbiol 47:1927–1930.
    95.
    Bourgeois N, Dehandschoewercker L, Bertout S, Bousquet PJ, Rispail P, Lachaud L. 2010. Antifungal susceptibility of 205 Candida spp. isolated primarily during invasive candidiasis and comparison of the Vitek 2 system with the CLSI broth microdilution and Etest methods. J Clin Microbiol 48:154–161.
    96.
    Cejudo MA, Gallego AG, Lacasa EC, Aller AI, Romero A, Garcia JP, Andres GQ, Martin-Mazuelos E. 2010. Evaluation of the VITEK 2 system to test the susceptibility of Candida spp., Trichosporon asahii and Cryptococcus neoformans to amphotericin B, flucytosine, fluconazole and voriconazole: a comparison with the M27-A3 reference method. Med Mycol 48:710–719.
    97.
    Cuenca-Estrella M, Gomez-Lopez A, Alastruey-Izquierdo A, Bernal-Martinez L, Cuesta I, Buitrago MJ, Rodriguez-Tudela JL. 2010. Comparison of the Vitek 2 antifungal susceptibility system with the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution reference methods and with the Sensititre YeastOne and Etest techniques for in vitro detection of antifungal resistance in yeast isolates. J Clin Microbiol 48:1782–1786.
    98.
    Farina C, Manso E, Andreoni S, Conte M, Fazii P, Lombardi G, Sanna S, Russello G. 2011. Interlaboratory evaluation of VITEK2 system and Sensititre YeastOne(R) for antifungal susceptibility testing of yeasts isolated from blood cultures against four antifungal agents. New Microbiol 34:195–201.
    99.
    Peterson JF, Pfaller MA, Diekema DJ, Rinaldi MG, Riebe KM, Ledeboer NA. 2011. Multicenter comparison of the Vitek 2 antifungal susceptibility test with the CLSI broth microdilution reference method for testing caspofungin, micafungin, and posaconazole against Candida spp. J Clin Microbiol 49:1765–1771.
    100.
    Astvad KM, Perlin DS, Johansen HK, Jensen RH, Arendrup MC. 2013. Evaluation of caspofungin susceptibility testing by the new Vitek 2 AST-YS06 yeast card using a unique collection of FKS wild-type and hot spot mutant isolates, including the five most common Candida species. Antimicrob Agents Chemother 57:177–182.
    101.
    Pfaller MA, Diekema DJ, Procop GW, Rinaldi MG. 2013. Comparison of the Vitek 2 yeast susceptibility system with CLSI microdilution for antifungal susceptibility testing of fluconazole and voriconazole against Candida spp., using new clinical breakpoints and epidemiological cutoff values. Diagn Microbiol Infect Dis 77:37–40.
    102.
    Mahabeer Y, Chang CC, Naidu D, Dorasamy A, Lewin S, Ndung'u T, Moosa M-Y, French M, Mlisana K, Coovadia Y. 2014. Comparison of Etests and Vitek 2 (R) to broth microdilution for the susceptibility testing of Cryptococcus neoformans. Diagn Microbiol Infect Dis 80:294–298.
    103.
    Pfaller MA, Diekema DJ, Procop GW, Wiederhold NP. 2014. Multicenter evaluation of the new Vitek 2 yeast susceptibility test using new CLSI clinical breakpoints for fluconazole. J Clin Microbiol 52:2126–2130.
    104.
    Rudensky B, Broidie E, Yinnon AM, Weitzman T, Paz E, Keller N, Raveh D. 2005. Rapid flow-cytometric susceptibility testing of Candida species. J Antimicrob Chemother 55:106–109.
    105.
    Wenisch C, Linnau KF, Parschalk B, Zedtwitz-Liebenstein K, Georgopoulos A. 1997. Rapid susceptibility testing of fungi by flow cytometry using vital staining. J Clin Microbiol 35:5–10.
    106.
    Wenisch C, Moore CB, Krause R, Presterl E, Pichna P, Denning DW. 2001. Antifungal susceptibility testing of fluconazole by flow cytometry correlates with clinical outcome. J Clin Microbiol 39:2458–2462.
    107.
    Ramani R, Chaturvedi V. 2000. Flow cytometry antifungal susceptibility testing of pathogenic yeasts other than Candida albicans and comparison with the NCCLS broth microdilution test. Antimicrob Agents Chemother 44:2752–2758.
    108.
    Peyron F, Favel A, Guiraud-Dauriac H, El Mzibri M, Chastin C, Dumenil G, Regli P. 1997. Evaluation of a flow cytofluorometric method for rapid determination of amphotericin B susceptibility of yeast isolates. Antimicrob Agents Chemother 41:1537–1540.
    109.
    Chaturvedi V, Ramani R, Pfaller MA. 2004. Collaborative study of the NCCLS and flow cytometry methods for antifungal susceptibility testing of Candida albicans. J Clin Microbiol 42:2249–2251.
    110.
    Pina-Vaz C, Sansonetty F, Rodrigues AG, Costa-Oliveira S, Tavares C, Martinez-de-Oliveira J. 2001. Cytometric approach for a rapid evaluation of susceptibility of Candida strains to antifungals. Clin Microbiol Infect 7:609–618.
    111.
    Mitchell M, Hudspeth M, Wright A. 2005. Flow cytometry susceptibility testing for the antifungal caspofungin. J Clin Microbiol 43:2586–2589.
    112.
    Vale-Silva LA, Pinto P, Lopes V, Ramos H, Pinto E. 2012. Comparison of the Etest and a rapid flow cytometry-based method with the reference CLSI broth microdilution protocol M27-A3 for the echinocandin susceptibility testing of Candida spp. Eur J Clin Microbiol Infect Dis 31:941–946.
    113.
    Wolk DM, Clark AE. 2018. Matrix-assisted laser desorption time of flight mass spectrometry. Clin Lab Med 38:471–486.
    114.
    Sanguinetti M, Posteraro B. 2016. Mass spectrometry applications in microbiology beyond microbe identification: progress and potential. Expert Rev Proteomics 13:965–977.
    115.
    Marinach C, Alanio A, Palous M, Kwasek S, Fekkar A, Brossas JY, Brun S, Snounou G, Hennequin C, Sanglard D, Datry A, Golmard JL, Mazier D. 2009. MALDI-TOF MS-based drug susceptibility testing of pathogens: the example of Candida albicans and fluconazole. Proteomics 9:4627–4631.
    116.
    De Carolis E, Vella A, Florio AR, Posteraro P, Perlin DS, Sanguinetti M, Posteraro B. 2012. Use of matrix-assisted laser desorption ionization-time of flight mass spectrometry for caspofungin susceptibility testing of Candida and Aspergillus species. J Clin Microbiol 50:2479–2483.
    117.
    Vatanshenassan M, Boekhout T, Lass-Florl C, Lackner M, Schubert S, Kostrzewa M, Sparbier K. 2018. Proof of concept for MBT ASTRA, a rapid matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based method to detect caspofungin resistance in Candida albicans and Candida glabrata. J Clin Microbiol 56:e00420-18.
    118.
    Saracli MA, Fothergill AW, Sutton DA, Wiederhold NP. 2015. Detection of triazole resistance among Candida species by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). Med Mycol 53:736–742.
    119.
    Vella A, De Carolis E, Vaccaro L, Posteraro P, Perlin DS, Kostrzewa M, Posteraro B, Sanguinetti M. 2013. Rapid antifungal susceptibility testing by matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis. J Clin Microbiol 51:2964–2969.
    120.
    Vella A, De Carolis E, Mello E, Perlin DS, Sanglard D, Sanguinetti M, Posteraro B. 2017. Potential use of MALDI-ToF mass spectrometry for rapid detection of antifungal resistance in the human pathogen Candida glabrata. Sci Rep 7:9099.
    121.
    Gitman MR, McTaggart L, Spinato J, Poopalarajah R, Lister E, Husain S, Kus JV. 2017. Antifungal susceptibility testing of Aspergillus spp. by using a composite correlation index (CCI)-based matrix-assisted laser desorption ionization-time of flight mass spectrometry method appears to not offer benefit over traditional broth microdilution testing. J Clin Microbiol 55:2030–2034.
    122.
    Chadwick SG, Schuyler JA, Vermitsky JP, Adelson ME, Mordechai E, Gygax SE. 2013. X-Plate Technology: a new method for detecting fluconazole resistance in Candida species. J Med Microbiol 62:720–726.
    123.
    de Vasconcelos AA, Jr, Menezes EA, Cunha FA. 2011. Chromogenic medium for direct susceptibility testing of Candida spp. isolated from urine. Mycopathologia 172:125–130.
    124.
    Kirkpatrick WR, Zimmerman JD, Haikal FP, Broker MJ, Brockway E, Fothergill AW, McCarthy DI, Patterson TF, Redding SW. 2010. Screening for drug-resistant Candida yeasts with chromogenic agar. Med Mycol 48:807–816.
    125.
    Tan GL, Peterson EM. 2005. CHROMagar Candida medium for direct susceptibility testing of yeast from blood cultures. J Clin Microbiol 43:1727–1731.
    126.
    Montesinos I, Argudin MA, Hites M, Ahajjam F, Dodemont M, Dagyaran C, Bakkali M, Etienne I, Jacobs F, Knoop C, Patteet S, Lagrou K. 2017. Culture-based methods and molecular tools for azole-resistant Aspergillus fumigatus detection in a Belgian university hospital. J Clin Microbiol 55:2391–2399.
    127.
    Bragazzi NL, Gasparini R, Amicizia D, Panatto D, Larosa C. 2015. Porous alumina as a promising biomaterial for public health. Adv Protein Chem Struct Biol 101:213–229.
    128.
    Ingham CJ, Boonstra S, Levels S, de Lange M, Meis JF, Schneeberger PM. 2012. Rapid susceptibility testing and microcolony analysis of Candida spp. cultured and imaged on porous aluminum oxide. PLoS One 7:e33818.
    129.
    Ingham CJ, Sprenkels A, Bomer J, Molenaar D, van den Berg A, van Hylckama Vlieg JE, de Vos WM. 2007. The micro-Petri dish, a million-well growth chip for the culture and high-throughput screening of microorganisms. Proc Natl Acad Sci U S A 104:18217–18222.
    130.
    Ingham CJ, Schneeberger PM. 2012. Microcolony imaging of Aspergillus fumigatus treated with echinocandins reveals both fungistatic and fungicidal activities. PLoS One 7:e35478.
    131.
    Ingham CJ, van den Ende M, Wever PC, Schneeberger PM. 2006. Rapid antibiotic sensitivity testing and trimethoprim-mediated filamentation of clinical isolates of the Enterobacteriaceae assayed on a novel porous culture support. J Med Microbiol 55:1511–1519.
    132.
    Manneck T, Braissant O, Haggenmuller Y, Keiser J. 2011. Isothermal microcalorimetry to study drugs against Schistosoma mansoni. J Clin Microbiol 49:1217–1225.
    133.
    Entenza JM, Betrisey B, Manuel O, Giddey M, Sakwinska O, Laurent F, Bizzini A. 2014. Rapid detection of Staphylococcus aureus strains with reduced susceptibility to vancomycin by isothermal microcalorimetry. J Clin Microbiol 52:180–186.
    134.
    Boillat-Blanco N, Furustrand Tafin U, Jaton K, Trampuz A. 2015. Susceptibility testing of Mycobacterium abscessus by isothermal microcalorimetry. Diagn Microbiol Infect Dis 83:139–143.
    135.
    Furustrand Tafin U, Clauss M, Hauser PM, Bille J, Meis JF, Trampuz A. 2012. Isothermal microcalorimetry: a novel method for real-time determination of antifungal susceptibility of Aspergillus species. Clin Microbiol Infect 18:E241–E245.
    136.
    Furustrand Tafin U, Meis JF, Trampuz A. 2013. Microcalorimetry assay for rapid detection of voriconazole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 57:5704–5706.
    137.
    Furustrand Tafin U, Meis JF, Trampuz A. 2012. Isothermal microcalorimetry for antifungal susceptibility testing of Mucorales, Fusarium spp., and Scedosporium spp. Diagn Microbiol Infect Dis 73:330–337.
    138.
    Maiolo EM, Furustrand Tafin U, Borens O, Trampuz A. 2014. Activities of fluconazole, caspofungin, anidulafungin, and amphotericin B on planktonic and biofilm Candida species determined by microcalorimetry. Antimicrob Agents Chemother 58:2709–2717.
    139.
    Rex JH, Pfaller MA. 2002. Has antifungal susceptibility testing come of age? Clin Infect Dis 35:982–989.
    140.
    Pfaller MA, Messer SA, Coffmann S. 1995. Comparison of visual and spectrophotometric methods of MIC endpoint determinations by using broth microdilution methods to test five antifungal agents, including the new triazole D0870. J Clin Microbiol 33:1094–1097.
    141.
    Pfaller MA, Messer SA, Bolmstrom A, Odds FC, Rex JH. 1996. Multisite reproducibility of the Etest MIC method for antifungal susceptibility testing of yeast isolates. J Clin Microbiol 34:1691–1693.
    142.
    Revankar SG, Kirkpatrick WR, McAtee RK, Fothergill AW, Redding SW, Rinaldi MG, Patterson TF. 1998. Interpretation of trailing endpoints in antifungal susceptibility testing by the National Committee for Clinical Laboratory Standards method. J Clin Microbiol 36:153–156.
    143.
    Marr KA, Rustad TR, Rex JH, White TC. 1999. The trailing end point phenotype in antifungal susceptibility testing is pH dependent. Antimicrob Agents Chemother 43:1383–1386.
    144.
    Arthington-Skaggs BA, Warnock DW, Morrison CJ. 2000. Quantitation of Candida albicans ergosterol content improves the correlation between in vitro antifungal susceptibility test results and in vivo outcome after fluconazole treatment in a murine model of invasive candidiasis. Antimicrob Agents Chemother 44:2081–2085.
    145.
    Arthington-Skaggs BA, Candidemia Active Surveillance Group, Lee-Yang W, Ciblak MA, Frade JP, Brandt ME, Hajjeh RA, Harrison LH, Sofair AN, Warnock DW. 2002. Comparison of visual and spectrophotometric methods of broth microdilution MIC end point determination and evaluation of a sterol quantitation method for in vitro susceptibility testing of fluconazole and itraconazole against trailing and nontrailing Candida isolates. Antimicrob Agents Chemother 46:2477–2481.
    146.
    Odds FC, Motyl M, Andrade R, Bille J, Canton E, Cuenca-Estrella M, Davidson A, Durussel C, Ellis D, Foraker E, Fothergill AW, Ghannoum MA, Giacobbe RA, Gobernado M, Handke R, Laverdiere M, Lee-Yang W, Merz WG, Ostrosky-Zeichner L, Peman J, Perea S, Perfect JR, Pfaller MA, Proia L, Rex JH, Rinaldi MG, Rodriguez-Tudela JL, Schell WA, Shields C, Sutton DA, Verweij PE, Warnock DW. 2004. Interlaboratory comparison of results of susceptibility testing with caspofungin against Candida and Aspergillus species. J Clin Microbiol 42:3475–3482.
    147.
    Fleischhacker M, Radecke C, Schulz B, Ruhnke M. 2008. Paradoxical growth effects of the echinocandins caspofungin and micafungin, but not of anidulafungin, on clinical isolates of Candida albicans and C. dubliniensis. Eur J Clin Microbiol Infect Dis 27:127–131.
    148.
    Chamilos G, Lewis RE, Albert N, Kontoyiannis DP. 2007. Paradoxical effect of echinocandins across Candida species in vitro: evidence for echinocandin-specific and candida species-related differences. Antimicrob Agents Chemother 51:2257–2259.
    149.
    Soczo G, Kardos G, Varga I, Kelentey B, Gesztelyi R, Majoros L. 2007. In vitro study of Candida tropicalis isolates exhibiting paradoxical growth in the presence of high concentrations of caspofungin. Antimicrob Agents Chemother 51:4474–4476.
    150.
    Stevens DA, Espiritu M, Parmar R. 2004. Paradoxical effect of caspofungin: reduced activity against Candida albicans at high drug concentrations. Antimicrob Agents Chemother 48:3407–3411.
    151.
    Stevens DA, White TC, Perlin DS, Selitrennikoff CP. 2005. Studies of the paradoxical effect of caspofungin at high drug concentrations. Diagn Microbiol Infect Dis 51:173–178.
    152.
    Eagle H, Musselman AD. 1948. The rate of bactericidal action of penicillin in vitro as a function of its concentration, and its paradoxically reduced activity at high concentrations against certain organisms. J Exp Med 88:99–131.
    153.
    Stevens DA, Ichinomiya M, Koshi Y, Horiuchi H. 2006. Escape of Candida from caspofungin inhibition at concentrations above the MIC (paradoxical effect) accomplished by increased cell wall chitin; evidence for beta-1,6-glucan synthesis inhibition by caspofungin. Antimicrob Agents Chemother 50:3160–3161.
    154.
    Clemons KV, Espiritu M, Parmar R, Stevens DA. 2006. Assessment of the paradoxical effect of caspofungin in therapy of candidiasis. Antimicrob Agents Chemother 50:1293–1297.
    155.
    Pfaller MA, Andes D, Arendrup MC, Diekema DJ, Espinel-Ingroff A, Alexander BD, Brown SD, Chaturvedi V, Fowler CL, Ghannoum MA, Johnson EM, Knapp CC, Motyl MR, Ostrosky-Zeichner L, Walsh TJ. 2011. Clinical breakpoints for voriconazole and Candida spp. revisited: review of microbiologic, molecular, pharmacodynamic, and clinical data as they pertain to the development of species-specific interpretive criteria. Diagn Microbiol Infect Dis 70:330–343.
    156.
    Pfaller MA, CLSI Subcommittee for Antifungal Testing, Diekema DJ, Andes D, Arendrup MC, Brown SD, Lockhart SR, Motyl M, Perlin DS. 2011. Clinical breakpoints for the echinocandins and Candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria. Drug Resist Updat 14:164–176.
    157.
    Pfaller MA, CLSI Subcommittee for Antifungal Susceptibility Testing, Andes D, Diekema DJ, Espinel-Ingroff A, Sheehan D. 2010. Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical breakpoints for fluconazole and Candida: time for harmonization of CLSI and EUCAST broth microdilution methods. Drug Resist Updat 13:180–195.
    158.
    European Committee on Antimicrobial Susceptibility Testing (EUCAST). 2018. Antifungal agents: breakpoint tables for interpretation of MICs, version 9.0. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/AFST/Clinical_breakpoints/Antifungal_breakpoints_v_9.0_180212.pdf.
    159.
    Arendrup MC, European Committee on Antimicrobial Susceptibility Testing-Subcommittee on Antifungal Susceptibility Testing (EUCAST-AFST), Cuenca-Estrella M, Lass-Flörl C, Hope WW. 2014. EUCAST technical note on Candida and micafungin, anidulafungin and fluconazole. Mycoses 57:377–379.
    160.
    Arendrup MC, European Committee on Antimicrobial Susceptibility Testing-Subcommittee on Antifungal Susceptibility Testing (EUCAST-AFST), Cuenca-Estrella M, Donnelly JP, Hope W, Lass-Flörl C, Rodriguez-Tudela J-L. 2011. EUCAST technical note on posaconazole. Clin Microbiol Infect 17:E16–E17.
    161.
    Lass-Florl C, European Committee on Antimicrobial Susceptibility Testing-Subcommittee on Antifungal Susceptibility Testing, Arendrup MC, Rodriguez-Tudela JL, Cuenca-Estrella M, Donnelly P, Hope W. 2011. EUCAST technical note on amphotericin B. Clin Microbiol Infect 17:E27–E29.
    162.
    European Committee on Antimicrobial Susceptibility Testing (EUCAST). 17 November 2017. Standard operating procedure: MIC distributions and the setting of epidemiological cut-off (ECOFF) values. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/EUCAST_SOPs/EUCAST_SOP_10.0_MIC_distributions_and_epidemiological_cut-off_value__ECOFF__setting_20171117.pdf.
    163.
    Clinical and Laboratory Standards Institute. 2016. Principles and procedures for the development of epidemiological cutoff values for antifungal susceptibility testing, 1st ed. Guideline M57. Clinical and Laboratory Standards Institute, Wayne, PA.
    164.
    Clinical and Laboratory Standards Institute. 2018. Epidemiological cutoff values for antifungal susceptibility testing, 2nd ed. Supplement M59. Clinical and Laboratory Standards Institute, Wayne, PA.
    165.
    Alexander BD, Johnson MD, Pfeiffer CD, Jimenez-Ortigosa C, Catania J, Booker R, Castanheira M, Messer SA, Perlin DS, Pfaller MA. 2013. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis 56:1724–1732.
    166.
    Shields RK, Nguyen MH, Press EG, Kwa AL, Cheng S, Du C, Clancy CJ. 2012. The presence of an FKS mutation rather than MIC is an independent risk factor for failure of echinocandin therapy among patients with invasive candidiasis due to Candida glabrata. Antimicrob Agents Chemother 56:4862–4869.
    167.
    Lockhart SR, Ghannoum MA, Alexander BD. 2017. Establishment and use of epidemiological cutoff values for molds and yeasts by use of the Clinical and Laboratory Standards Institute M57 standard. J Clin Microbiol 55:1262–1268.
    168.
    Odds FC, Brown AJ, Gow NA. 2003. Antifungal agents: mechanisms of action. Trends Microbiol 11:272–279.
    169.
    Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A. 2017. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis 17:e383–e392.
    170.
    Lockhart SR, Iqbal N, Cleveland AA, Farley MM, Harrison LH, Bolden CB, Baughman W, Stein B, Hollick R, Park BJ, Chiller T. 2012. Species identification and antifungal susceptibility testing of Candida bloodstream isolates from population-based surveillance studies in two U.S. cities from 2008 to 2011. J Clin Microbiol 50:3435–3442.
    171.
    Hesstvedt L, Norwegian Yeast Study Group, Gaustad P, Andersen CT, Haarr E, Hannula R, Haukland HH, Hermansen NO, Larssen KW, Mylvaganam H, Ranheim TE, Sandven P, Nordoy I, Norwegian Yeast Study G, Kanestrom A, Grub C, Onken A, Thielsen C, Skaare D, Tofteland S, Sonsteby LJ, Hjetland R, Hide R, Vik E, Kummel A, Asheim S. 2015. Twenty-two years of candidaemia surveillance: results from a Norwegian national study. Clin Microbiol Infect 21:938–945.
    172.
    Orasch C, Marchetti O, Garbino J, Schrenzel J, Zimmerli S, Muhlethaler K, Pfyffer G, Ruef C, Fehr J, Zbinden R, Calandra T, Bille J, Funginos. 2014. Candida species distribution and antifungal susceptibility testing according to European Committee on Antimicrobial Susceptibility Testing and new vs. old Clinical and Laboratory Standards Institute clinical breakpoints: a 6-year prospective candidaemia survey from the fungal infection network of Switzerland. Clin Microbiol Infect 20:698–705.
    173.
    Tan TY, Hsu LY, Alejandria MM, Chaiwarith R, Chinniah T, Chayakulkeeree M, Choudhury S, Chen YH, Shin JH, Kiratisin P, Mendoza M, Prabhu K, Supparatpinyo K, Tan AL, Phan XT, Tran TT, Nguyen GB, Doan MP, Huynh VA, Nguyen SM, Tran TB, Van Pham H. 2016. Antifungal susceptibility of invasive Candida bloodstream isolates from the Asia-Pacific region. Med Mycol 54:471–477.
    174.
    Chakrabarti A, Sood P, Rudramurthy SM, Chen S, Kaur H, Capoor M, Chhina D, Rao R, Eshwara VK, Xess I, Kindo AJ, Umabala P, Savio J, Patel A, Ray U, Mohan S, Iyer R, Chander J, Arora A, Sardana R, Roy I, Appalaraju B, Sharma A, Shetty A, Khanna N, Marak R, Biswas S, Das S, Harish BN, Joshi S, Mendiratta D. 2015. Incidence, characteristics and outcome of ICU-acquired candidemia in India. Intensive Care Med 41:285–295.
    175.
    Chapman B, Slavin M, Marriott D, Halliday C, Kidd S, Arthur I, Bak N, Heath CH, Kennedy K, Morrissey CO, Sorrell TC, van Hal S, Keighley C, Goeman E, Underwood N, Hajkowicz K, Hofmeyr A, Leung M, Macesic N, Botes J, Blyth C, Cooley L, George CR, Kalukottege P, Kesson A, McMullan B, Baird R, Robson J, Korman TM, Pendle S, Weeks K, Liu E, Cheong E, Chen S, Australian and New Zealand Mycoses Interest Group. 2017. Changing epidemiology of candidaemia in Australia. J Antimicrob Chemother 72:1103–1108.
    176.
    Hii IM, Chang HL, Lin LC, Lee YL, Liu YM, Liu CE, Chen CH, Cheng YR, Chang CY. 2015. Changing epidemiology of candidemia in a medical center in middle Taiwan. J Microbiol Immunol Infect 48:306–315.
    177.
    Trouve C, Blot S, Hayette MP, Jonckheere S, Patteet S, Rodriguez-Villalobos H, Symoens F, Van Wijngaerden E, Lagrou K. 2017. Epidemiology and reporting of candidaemia in Belgium: a multi-centre study. Eur J Clin Microbiol Infect Dis 36:649–655.
    178.
    Castanheira M, Deshpande LM, Davis AP, Rhomberg PR, Pfaller MA. 2017. Monitoring antifungal resistance in a global collection of invasive yeasts and molds: application of CLSI epidemiological cutoff values and whole-genome sequencing analysis for detection of azole resistance in Candida albicans. Antimicrob Agents Chemother 61:e00906-17.
    179.
    Vallabhaneni S, Cleveland AA, Farley MM, Harrison LH, Schaffner W, Beldavs ZG, Derado G, Pham CD, Lockhart SR, Smith RM. 2015. Epidemiology and risk factors for echinocandin nonsusceptible Candida glabrata bloodstream infections: data from a large multisite population-based candidemia surveillance program, 2008–2014. Open Forum Infect Dis 2:ofv163.
    180.
    Pfaller MA, Castanheira M, Lockhart SR, Ahlquist AM, Messer SA, Jones RN. 2012. Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata. J Clin Microbiol 50:1199–1203.
    181.
    Klotz U, Schmidt D, Willinger B, Steinmann E, Buer J, Rath PM, Steinmann J. 2016. Echinocandin resistance and population structure of invasive Candida glabrata isolates from two university hospitals in Germany and Austria. Mycoses 59:312–318.
    182.
    Lepak AJ, Zhao M, Berkow EL, Lockhart SR, Andes DR. 2017. Pharmacodynamic optimization for treatment of invasive Candida auris infection. Antimicrob Agents Chemother 61:e00791-17.
    183.
    Verweij PE, Chowdhary A, Melchers WJ, Meis JF. 2016. Azole resistance in Aspergillus fumigatus: can we retain the clinical use of mold-active antifungal azoles? Clin Infect Dis 62:362–368.
    184.
    Verweij PE, Mellado E, Melchers WJ. 2007. Multiple-triazole-resistant aspergillosis. N Engl J Med 356:1481–1483.
    185.
    Verweij PE, Snelders E, Kema GH, Mellado E, Melchers WJ. 2009. Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use? Lancet Infect Dis 9:789–795.
    186.
    Chowdhary A, Kathuria S, Xu J, Meis JF. 2013. Emergence of azole-resistant aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health. PLoS Pathog 9:e1003633.
    187.
    Bader O, Tünnermann J, Dudakova A, Tangwattanachuleeporn M, Weig M, Groß U. 2015. Environmental isolates of azole-resistant Aspergillus fumigatus in Germany. Antimicrob Agents Chemother 59:4356–4359.
    188.
    Chowdhary A, Sharma C, van den Boom M, Yntema JB, Hagen F, Verweij PE, Meis JF. 2014. Multi-azole-resistant Aspergillus fumigatus in the environment in Tanzania. J Antimicrob Chemother 69:2979–2983.
    189.
    Chowdhary A, Sharma C, Kathuria S, Hagen F, Meis JF. 2015. Prevalence and mechanism of triazole resistance in Aspergillus fumigatus in a referral chest hospital in Delhi, India and an update of the situation in Asia. Front Microbiol 6:428.
    190.
    Kidd SE, Goeman E, Meis JF, Slavin MA, Verweij PE. 2015. Multi-triazole-resistant Aspergillus fumigatus infections in Australia. Mycoses 58:350–355.
    191.
    Lavergne RA, Morio F, Favennec L, Dominique S, Meis JF, Gargala G, Verweij PE, Le Pape P. 2015. First description of azole-resistant Aspergillus fumigatus due to TR46/Y121F/T289A mutation in France. Antimicrob Agents Chemother 59:4331–4335.
    192.
    Le Pape P, Lavergne RA, Morio F, Alvarez-Moreno C. 2016. Multiple fungicide-driven alterations in azole-resistant Aspergillus fumigatus, Colombia, 2015. Emerg Infect Dis 22:156–157.
    193.
    Lockhart SR, Frade JP, Etienne KA, Pfaller MA, Diekema DJ, Balajee SA. 2011. Azole resistance in Aspergillus fumigatus isolates from the ARTEMIS global surveillance study is primarily due to the TR/L98H mutation in the cyp51A gene. Antimicrob Agents Chemother 55:4465–4468.
    194.
    Vermeulen E, Maertens J, De Bel A, Nulens E, Boelens J, Surmont I, Mertens A, Boel A, Lagrou K. 2015. Nationwide surveillance of azole resistance in aspergillus diseases. Antimicrob Agents Chemother 59:4569–4576.
    195.
    Mylonakis E, Clancy CJ, Ostrosky-Zeichner L, Garey KW, Alangaden GJ, Vazquez JA, Groeger JS, Judson MA, Vinagre YM, Heard SO, Zervou FN, Zacharioudakis IM, Kontoyiannis DP, Pappas PG. 2015. T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Clin Infect Dis 60:892–899.
    196.
    Wallet F, Nseir S, Baumann L, Herwegh S, Sendid B, Boulo M, Roussel-Delvallez M, Durocher AV, Courcol RJ. 2010. Preliminary clinical study using a multiplex real-time PCR test for the detection of bacterial and fungal DNA directly in blood. Clin Microbiol Infect 16:774–779.
    197.
    Chong GL, van de Sande WW, Dingemans GJ, Gaajetaan GR, Vonk AG, Hayette MP, van Tegelen DW, Simons GF, Rijnders BJ. 2015. Validation of a new Aspergillus real-time PCR assay for direct detection of Aspergillus and azole resistance of Aspergillus fumigatus on bronchoalveolar lavage fluid. J Clin Microbiol 53:868–874.
    198.
    Dannaoui E, Gabriel F, Gaboyard M, Lagardere G, Audebert L, Quesne G, Godichaud S, Verweij PE, Accoceberry I, Bougnoux ME. 2017. Molecular diagnosis of invasive aspergillosis and detection of azole resistance by a newly commercialized PCR kit. J Clin Microbiol 55:3210–3218.
    199.
    Perlin DS. 2007. Resistance to echinocandin-class antifungal drugs. Drug Resist Updat 10:121–130.
    200.
    Park S, Kelly R, Kahn JN, Robles J, Hsu MJ, Register E, Li W, Vyas V, Fan H, Abruzzo G, Flattery A, Gill C, Chrebet G, Parent SA, Kurtz M, Teppler H, Douglas CM, Perlin DS. 2005. Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates. Antimicrob Agents Chemother 49:3264–3273.
    201.
    Douglas CM, D'Ippolito JA, Shei GJ, Meinz M, Onishi J, Marrinan JA, Li W, Abruzzo GK, Flattery A, Bartizal K, Mitchell A, Kurtz MB. 1997. Identification of the FKS1 gene of Candida albicans as the essential target of 1,3-beta-d-glucan synthase inhibitors. Antimicrob Agents Chemother 41:2471–2479.
    202.
    Balashov SV, Park S, Perlin DS. 2006. Assessing resistance to the echinocandin antifungal drug caspofungin in Candida albicans by profiling mutations in FKS1. Antimicrob Agents Chemother 50:2058–2063.
    203.
    Pham CD, Bolden CB, Kuykendall RJ, Lockhart SR. 2014. Development of a Luminex-based multiplex assay for detection of mutations conferring resistance to echinocandins in Candida glabrata. J Clin Microbiol 52:790–795.
    204.
    Zhao Y, Nagasaki Y, Kordalewska M, Press EG, Shields RK, Nguyen MH, Clancy CJ, Perlin DS. 2016. Rapid detection of FKS-associated echinocandin resistance in Candida glabrata. Antimicrob Agents Chemother 60:6573–6577.
    205.
    Berkow EL, Lockhart SR. 2017. Fluconazole resistance in Candida species: a current perspective. Infect Drug Resist 10:237–245.
    206.
    Cowen LE, Sanglard D, Howard SJ, Rogers PD, Perlin DS. 2014. Mechanisms of antifungal drug resistance. Cold Spring Harb Perspect Med 5:a019752.
    207.
    van der Linden JW, Snelders E, Arends JP, Daenen SM, Melchers WJ, Verweij PE. 2010. Rapid diagnosis of azole-resistant aspergillosis by direct PCR using tissue specimens. J Clin Microbiol 48:1478–1480.
    208.
    Denning DW, Park S, Lass-Florl C, Fraczek MG, Kirwan M, Gore R, Smith J, Bueid A, Moore CB, Bowyer P, Perlin DS. 2011. High-frequency triazole resistance found in nonculturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis 52:1123–1129.
    209.
    Zhao Y, Stensvold CR, Perlin DS, Arendrup MC. 2013. Azole resistance in Aspergillus fumigatus from bronchoalveolar lavage fluid samples of patients with chronic diseases. J Antimicrob Chemother 68:1497–1504.
    210.
    Buil JB, Zoll J, Verweij PE, Melchers W. 2018. Molecular detection of azole-resistant Aspergillus fumigatus in clinical samples. Front Microbiol 9:515.
    211.
    Lestrade PP, Meis JF, Arends JP, van der Beek MT, de Brauwer E, van Dijk K, de Greeff SC, Haas PJ, Hodiamont CJ, Kuijper EJ, Leenstra T, Muller AE, Oude Lashof AM, Rijnders BJ, Roelofsen E, Rozemeijer W, Tersmette M, Terveer EM, Verduin CM, Wolfhagen MJ, Melchers WJ, Verweij PE. 2016. Diagnosis and management of aspergillosis in the Netherlands: a national survey. Mycoses 59:101–107.
    212.
    Chowdhary A, Sharma C, Meis JF. 2017. Azole-resistant aspergillosis: epidemiology, molecular mechanisms, and treatment. J Infect Dis 216:S436–S444.
    213.
    Patterson TF, Thompson GR, III, Denning DW, Fishman JA, Hadley S, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Nguyen MH, Segal BH, Steinbach WJ, Stevens DA, Walsh TJ, Wingard JR, Young JA, Bennett JE. 2016. Executive summary: practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 63:433–442.
    214.
    Perfect JR. 2017. The antifungal pipeline: a reality check. Nat Rev Drug Discov 16:603–616.

    Author Bios

    Elizabeth L. Berkow
    Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
    Elizabeth L. Berkow is the Director of the Fungal Reference Laboratory and the Laboratory Team Lead for the Mycotic Diseases Branch at the CDC, where her primary interests are antifungal susceptibility testing and mechanisms of antifungal drug resistance. She also serves the Antibiotic Resistance Laboratory Network (ARLN) at the CDC as a mycology subject matter expert and is a member of the Subcommittee on Antifungal Susceptibility Tests for CLSI. Dr. Berkow has a degree in Clinical Laboratory Science (M.S.) and earned her Ph.D. in Molecular Biology from the University of Tennessee Health Science Center in Memphis, TN. She is an ASCP board-certified medical laboratory scientist.
    Shawn R. Lockhart
    Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
    Shawn R. Lockhart received his Ph.D. from the University of Kentucky and then became a research scientist at the University of Iowa. He became a diplomat of the American Board of Medical Microbiology following a fellowship at the University of Iowa Hospitals and Clinics. Dr. Lockhart joined the CDC in 2008 as the director of the Fungal Reference Laboratory. He is currently Senior Clinical Laboratory Advisor and Senior Advisor for AMR for the Mycotic Diseases Branch at the CDC. He started studying Candida after it was determined to be the cause of death of a close family member. He has been interested in antifungal susceptibility testing since 2006 and has been involved with the Clinical and Laboratory Standards Institute Antifungal Subcommittee since 2009.
    Luis Ostrosky-Zeichner
    Division of Infectious Diseases, University of Texas Health Science Center, Houston, Texas, USA
    Luis Ostrosky-Zeichner, M.D., is a professor of medicine and epidemiology, the Vice-Chair of Medicine for Quality, and the director of the Laboratory of Mycology Research at McGovern Medical School. He obtained his medical degree from Universidad Nacional Autonoma de Mexico. He completed his internal medicine residency at Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran and his infectious diseases fellowship at the University of Texas Medical School at Houston and MD Anderson Cancer Center. He is a fellow of the American College of Physicians, the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, and the Academy of the European Confederation of Medical Mycology. He is a board member of the Mycoses Study Group and the International Immunocompromised Host Society. He has advanced training and experience in medical mycology, healthcare epidemiology, transplant infectious diseases, and healthcare quality.

    Information & Contributors

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    Clinical Microbiology Reviews
    Volume 33Number 317 June 2020
    eLocator: e00069-19

    History

    Published online: 29 April 2020

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    KEYWORDS

    1. antifungal susceptibility testing
    2. CLSI
    3. EUCAST
    4. epidemiological cutoff value
    5. breakpoints
    6. antifungal resistance

    Contributors

    Authors

    Elizabeth L. Berkow
    Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
    Shawn R. Lockhart
    Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
    Luis Ostrosky-Zeichner
    Division of Infectious Diseases, University of Texas Health Science Center, Houston, Texas, USA

    Notes

    Address correspondence to Elizabeth L. Berkow, [email protected].

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  • Clinical Microbiology ReviewsArticle
    Survival of the Fittest: How Bacterial Pathogens Utilize Bile To Enhance Infection

    Survival of the Fittest: How Bacterial Pathogens Utilize Bile To Enhance Infection

    SUMMARY

    Bacterial pathogens have coevolved with humans in order to efficiently infect, replicate within, and be transmitted to new hosts to ensure survival and a continual infection cycle. For enteric pathogens, the ability to adapt to numerous host factors under the harsh conditions of the gastrointestinal tract is critical for establishing infection. One such host factor readily encountered by enteric bacteria is bile, an innately antimicrobial detergent-like compound essential for digestion and nutrient absorption. Not only have enteric pathogens evolved to resist the bactericidal conditions of bile, but these bacteria also utilize bile as a signal to enhance virulence regulation for efficient infection. This review provides a comprehensive and up-to-date analysis of bile-related research with enteric pathogens. From common responses to the unique expression of specific virulence factors, each pathogen has overcome significant challenges to establish infection in the gastrointestinal tract. Utilization of bile as a signal to modulate virulence factor expression has led to important insights for our understanding of virulence mechanisms for many pathogens. Further research on enteric pathogens exposed to this in vivo signal will benefit therapeutic and vaccine development and ultimately enhance our success at combating such elite pathogens.

    REFERENCES

    1.
    Elliott DE, Siddique SS, Weinstock JV. 2014. Innate immunity in disease. Clin Gastroenterol Hepatol 12:749–755.
    2.
    Hong W, Wu YE, Fu X, Chang Z. 2012. Chaperone-dependent mechanisms for acid resistance in enteric bacteria. Trends Microbiol 20:328–335.
    3.
    Begley M, Gahan CG, Hill C. 2005. The interaction between bacteria and bile. FEMS Microbiol Rev 29:625–651.
    4.
    Merritt ME, Donaldson JR. 2009. Effect of bile salts on the DNA and membrane integrity of enteric bacteria. J Med Microbiol 58:1533–1541.
    5.
    Kortman GA, Boleij A, Swinkels DW, Tjalsma H. 2012. Iron availability increases the pathogenic potential of Salmonella Typhimurium and other enteric pathogens at the intestinal epithelial interface. PLoS One 7:e29968.
    6.
    Sandrini S, Masania R, Zia F, Haigh R, Freestone P. 2013. Role of porin proteins in acquisition of transferrin iron by enteropathogens. Microbiology 159:2639–2650.
    7.
    Yu LC, Wang JT, Wei SC, Ni YH. 2012. Host-microbial interactions and regulation of intestinal epithelial barrier function: from physiology to pathology. World J Gastrointest Pathophysiol 3:27–43.
    8.
    Reshetnyak VI. 2013. Physiological and molecular biochemical mechanisms of bile formation. World J Gastroenterol 19:7341–7360.
    9.
    Ridlon JM, Kang DJ, Hylemon PB. 2006. Bile salt biotransformations by human intestinal bacteria. J Lipid Res 47:241–259.
    10.
    Hamer HM, De Preter V, Windey K, Verbeke K. 2012. Functional analysis of colonic bacterial metabolism: relevant to health? Am J Physiol Gastrointest Liver Physiol 302:G1–G9.
    11.
    Kristoffersen SM, Ravnum S, Tourasse NJ, Okstad OA, Kolsto AB, Davies W. 2007. Low concentrations of bile salts induce stress responses and reduce motility in Bacillus cereus ATCC 14579 [corrected]. J Bacteriol 189:5302–5313.
    12.
    Ding JW, Andersson R, Soltesz V, Willen R, Bengmark S. 1993. The role of bile and bile acids in bacterial translocation in obstructive jaundice in rats. Eur Surg Res 25:11–19.
    13.
    Slocum MM, Sittig KM, Specian RD, Deitch EA. 1992. Absence of intestinal bile promotes bacterial translocation. Am Surg 58:305–310.
    14.
    Lisowska A, Kobelska-Dubiel N, Jankowska I, Pawlowska J, Moczko J, Walkowiak J. 2014. Small intestinal bacterial overgrowth in patients with progressive familial intrahepatic cholestasis. Acta Biochim Pol 61:103–107.
    15.
    Mayo SA, Song YK, Cruz MR, Phan TM, Singh KV, Garsin DA, Murray BE, Dial EJ, Lichtenberger LM. 2016. Indomethacin injury to the rat small intestine is dependent upon biliary secretion and is associated with overgrowth of enterococci. Physiol Rep 4:e12725.
    16.
    Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. 2005. Diversity of the human intestinal microbial flora. Science 308:1635–1638.
    17.
    Kaper JB, Nataro JP, Mobley HL. 2004. Pathogenic Escherichia coli. Nat Rev Microbiol 2:123–140.
    18.
    Hughes DT, Sperandio V. 2008. Inter-kingdom signalling: communication between bacteria and their hosts. Nat Rev Microbiol 6:111–120.
    19.
    Croxen MA, Law RJ, Scholz R, Keeney KM, Wlodarska M, Finlay BB. 2013. Recent advances in understanding enteric pathogenic Escherichia coli. Clin Microbiol Rev 26:822–880.
    20.
    Torres AG, Tutt CB, Duval L, Popov V, Nasr AB, Michalski J, Scaletsky IC. 2007. Bile salts induce expression of the afimbrial LDA adhesin of atypical enteropathogenic Escherichia coli. Cell Microbiol 9:1039–1049.
    21.
    Rosenberg EY, Bertenthal D, Nilles ML, Bertrand KP, Nikaido H. 2003. Bile salts and fatty acids induce the expression of Escherichia coli AcrAB multidrug efflux pump through their interaction with Rob regulatory protein. Mol Microbiol 48:1609–1619.
    22.
    Thanassi DG, Cheng LW, Nikaido H. 1997. Active efflux of bile salts by Escherichia coli. J Bacteriol 179:2512–2518.
    23.
    Kus JV, Gebremedhin A, Dang V, Tran SL, Serbanescu A, Barnett Foster D. 2011. Bile salts induce resistance to polymyxin in enterohemorrhagic Escherichia coli O157:H7. J Bacteriol 193:4509–4515.
    24.
    Sahl JW, Rasko DA. 2012. Analysis of global transcriptional profiles of enterotoxigenic Escherichia coli isolate E24377A. Infect Immun 80:1232–1242.
    25.
    de Jesus MC, Urban AA, Marasigan ME, Barnett Foster DE. 2005. Acid and bile-salt stress of enteropathogenic Escherichia coli enhances adhesion to epithelial cells and alters glycolipid receptor binding specificity. J Infect Dis 192:1430–1440.
    26.
    Barnett Foster D. 2013. Modulation of the enterohemorrhagic E. coli virulence program through the human gastrointestinal tract. Virulence 4:315–323.
    27.
    Arenas-Hernandez MM, Rojas-Lopez M, Medrano-Lopez A, Nunez-Reza KJ, Puente JL, Martinez-Laguna Y, Torres AG. 2014. Environmental regulation of the long polar fimbriae 2 of enterohemorrhagic Escherichia coli O157:H7. FEMS Microbiol Lett 357:105–114.
    28.
    Froelich JM, Tran K, Wall D. 2006. A pmrA constitutive mutant sensitizes Escherichia coli to deoxycholic acid. J Bacteriol 188:1180–1183.
    29.
    Hofmann AF, Hagey LR. 2008. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci 65:2461–2483.
    30.
    Kramer VC, Nickerson KW, Hamlett NV, O'Hara C. 1984. Prevalence of extreme detergent resistance among the Enterobacteriaceae. Can J Microbiol 30:711–713.
    31.
    D'Mello A, Yotis WW. 1987. The action of sodium deoxycholate on Escherichia coli. Appl Environ Microbiol 53:1944–1946.
    32.
    Jacobsen L, Durso L, Conway T, Nickerson KW. 2009. Escherichia coli O157:H7 and other E. coli strains share physiological properties associated with intestinal colonization. Appl Environ Microbiol 75:4633–4635.
    33.
    De Paepe M, Gaboriau-Routhiau V, Rainteau D, Rakotobe S, Taddei F, Cerf-Bensussan N. 2011. Trade-off between bile resistance and nutritional competence drives Escherichia coli diversification in the mouse gut. PLoS Genet 7:e1002107.
    34.
    Kwan BW, Lord DM, Peti W, Page R, Benedik MJ, Wood TK. 14 February 2015. The MqsR/MqsA toxin/antitoxin system protects Escherichia coli during bile acid stress. Environ Microbiol doi:
    35.
    Bernstein C, Bernstein H, Payne CM, Beard SE, Schneider J. 1999. Bile salt activation of stress response promoters in Escherichia coli. Curr Microbiol 39:68–72.
    36.
    Foster PL. 2007. Stress-induced mutagenesis in bacteria. Crit Rev Biochem Mol Biol 42:373–397.
    37.
    Kandell RL, Bernstein C. 1991. Bile salt/acid induction of DNA damage in bacterial and mammalian cells: implications for colon cancer. Nutr Cancer 16:227–238.
    38.
    Sengupta C, Ray S, Chowdhury R. 2014. Fine tuning of virulence regulatory pathways in enteric bacteria in response to varying bile and oxygen concentrations in the gastrointestinal tract. Gut Pathog 6:38.
    39.
    Hamner S, McInnerney K, Williamson K, Franklin MJ, Ford TE. 2013. Bile salts affect expression of Escherichia coli O157:H7 genes for virulence and iron acquisition, and promote growth under iron limiting conditions. PLoS One 8:e74647.
    40.
    Qadri F, Svennerholm AM, Faruque AS, Sack RB. 2005. Enterotoxigenic Escherichia coli in developing countries: epidemiology, microbiology, clinical features, treatment, and prevention. Clin Microbiol Rev 18:465–483.
    41.
    Binsztein N, Jouve MJ, Viboud GI, Lopez Moral L, Rivas M, Orskov I, Ahren C, Svennerholm AM. 1991. Colonization factors of enterotoxigenic Escherichia coli isolated from children with diarrhea in Argentina. J Clin Microbiol 29:1893–1898.
    42.
    Gaastra W, Svennerholm AM. 1996. Colonization factors of human enterotoxigenic Escherichia coli (ETEC). Trends Microbiol 4:444–452.
    43.
    von Mentzer A, Connor TR, Wieler LH, Semmler T, Iguchi A, Thomson NR, Rasko DA, Joffre E, Corander J, Pickard D, Wiklund G, Svennerholm AM, Sjoling A, Dougan G. 2014. Identification of enterotoxigenic Escherichia coli (ETEC) clades with long-term global distribution. Nat Genet 46:1321–1326.
    44.
    Nicklasson M, Sjoling A, von Mentzer A, Qadri F, Svennerholm AM. 2012. Expression of colonization factor CS5 of enterotoxigenic Escherichia coli (ETEC) is enhanced in vivo and by the bile component Na glycocholate hydrate. PLoS One 7:e35827.
    45.
    Grewal HM, Valvatne H, Bhan MK, van Dijk L, Gaastra W, Sommerfelt H. 1997. A new putative fimbrial colonization factor, CS19, of human enterotoxigenic Escherichia coli. Infect Immun 65:507–513.
    46.
    Sommerfelt H, Grewal HM, Svennerholm AM, Gaastra W, Flood PR, Viboud G, Bhan MK. 1992. Genetic relationship of putative colonization factor O166 to colonization factor antigen I and coli surface antigen 4 of enterotoxigenic Escherichia coli. Infect Immun 60:3799–3806.
    47.
    Chatterjee A, Chowdhury R. 2008. Bile and unsaturated fatty acids inhibit the binding of cholera toxin and Escherichia coli heat-labile enterotoxin to GM1 receptor. Antimicrob Agents Chemother 52:220–224.
    48.
    Gabig M, Herman-Antosiewicz A, Kwiatkowska M, Los M, Thomas MS, Wegrzyn G. 2002. The cell surface protein Ag43 facilitates phage infection of Escherichia coli in the presence of bile salts and carbohydrates. Microbiology 148:1533–1542.
    49.
    Romao FT, Hernandes RT, Yamamoto D, Osugui L, Popi A, Gomes TA. 2014. Influence of environmental factors in the adherence of an atypical enteropathogenic Escherichia coli strain to epithelial cells. BMC Microbiol 14:299.
    50.
    Annaba F, Sarwar Z, Gill RK, Ghosh A, Saksena S, Borthakur A, Hecht GA, Dudeja PK, Alrefai WA. 2012. Enteropathogenic Escherichia coli inhibits ileal sodium-dependent bile acid transporter ASBT. Am J Physiol Gastrointest Liver Physiol 302:G1216–G1222.
    51.
    Alrefai WA, Gill RK. 2007. Bile acid transporters: structure, function, regulation and pathophysiological implications. Pharm Res 24:1803–1823.
    52.
    Goosney DL, Celli J, Kenny B, Finlay BB. 1999. Enteropathogenic Escherichia coli inhibits phagocytosis. Infect Immun 67:490–495.
    53.
    Bauer ME, Welch RA. 1996. Characterization of an RTX toxin from enterohemorrhagic Escherichia coli O157:H7. Infect Immun 64:167–175.
    54.
    Torres AG, Kaper JB. 2003. Multiple elements controlling adherence of enterohemorrhagic Escherichia coli O157:H7 to HeLa cells. Infect Immun 71:4985–4995.
    55.
    Chassaing B, Etienne-Mesmin L, Bonnet R, Darfeuille-Michaud A. 2013. Bile salts induce long polar fimbriae expression favouring Crohn's disease-associated adherent-invasive Escherichia coli interaction with Peyer's patches. Environ Microbiol 15:355–371.
    56.
    Schroeder GN, Hilbi H. 2008. Molecular pathogenesis of Shigella spp.: controlling host cell signaling, invasion, and death by type III secretion. Clin Microbiol Rev 21:134–156.
    57.
    Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acacio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM. 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382:209–222.
    58.
    Pope LM, Reed KE, Payne SM. 1995. Increased protein secretion and adherence to HeLa cells by Shigella spp. following growth in the presence of bile salts. Infect Immun 63:3642–3648.
    59.
    Hale TL, Sansonetti PJ, Schad PA, Austin S, Formal SB. 1983. Characterization of virulence plasmids and plasmid-associated outer membrane proteins in Shigella flexneri, Shigella sonnei, and Escherichia coli. Infect Immun 40:340–350.
    60.
    Olive AJ, Kenjale R, Espina M, Moore DS, Picking WL, Picking WD. 2007. Bile salts stimulate recruitment of IpaB to the Shigella flexneri surface, where it colocalizes with IpaD at the tip of the type III secretion needle. Infect Immun 75:2626–2629.
    61.
    Stensrud KF, Adam PR, La Mar CD, Olive AJ, Lushington GH, Sudharsan R, Shelton NL, Givens RS, Picking WL, Picking WD. 2008. Deoxycholate interacts with IpaD of Shigella flexneri in inducing the recruitment of IpaB to the type III secretion apparatus needle tip. J Biol Chem 283:18646–18654.
    62.
    Barta ML, Guragain M, Adam P, Dickenson NE, Patil M, Geisbrecht BV, Picking WL, Picking WD. 2012. Identification of the bile salt binding site on IpaD from Shigella flexneri and the influence of ligand binding on IpaD structure. Proteins 80:935–945.
    63.
    Dickenson NE, Zhang L, Epler CR, Adam PR, Picking WL, Picking WD. 2011. Conformational changes in IpaD from Shigella flexneri upon binding bile salts provide insight into the second step of type III secretion. Biochemistry 50:172–180.
    64.
    Dickenson NE, Arizmendi O, Patil MK, Toth RT, IV, Middaugh CR, Picking WD, Picking WL. 2013. N-terminus of IpaB provides a potential anchor to the Shigella type III secretion system tip complex protein IpaD. Biochemistry 52:8790–8799.
    65.
    Faherty CS, Redman JC, Rasko DA, Barry EM, Nataro JP. 2012. Shigella flexneri effectors OspE1 and OspE2 mediate induced adherence to the colonic epithelium following bile salts exposure. Mol Microbiol 85:107–121.
    66.
    Cary JW, Linz JE, Bhatnagar D. 1999. Microbial foodborne diseases: mechanisms of pathogenesis and toxin synthesis. CRC Press, Boca Raton, FL.
    67.
    Austin B. 2010. Vibrios as causal agents of zoonoses. Vet Microbiol 140:310–317.
    68.
    Faruque SM, Albert MJ, Mekalanos JJ. 1998. Epidemiology, genetics, and ecology of toxigenic Vibrio cholerae. Microbiol Mol Biol Rev 62:1301–1314.
    69.
    Yildiz FH, Visick KL. 2009. Vibrio biofilms: so much the same yet so different. Trends Microbiol 17:109–118.
    70.
    Butt AA, Aldridge KE, Sanders CV. 2004. Infections related to the ingestion of seafood part I: viral and bacterial infections. Lancet Infect Dis 4:201–212.
    71.
    Peterson KM. 2002. Expression of Vibrio cholerae virulence genes in response to environmental signals. Curr Issues Intest Microbiol 3:29–38.
    72.
    Provenzano D, Schuhmacher DA, Barker JL, Klose KE. 2000. The virulence regulatory protein ToxR mediates enhanced bile resistance in Vibrio cholerae and other pathogenic Vibrio species. Infect Immun 68:1491–1497.
    73.
    Duret G, Delcour AH. 2006. Deoxycholic acid blocks Vibrio cholerae OmpT but not OmpU porin. J Biol Chem 281:19899–19905.
    74.
    Simonet VC, Basle A, Klose KE, Delcour AH. 2003. The Vibrio cholerae porins OmpU and OmpT have distinct channel properties. J Biol Chem 278:17539–17545.
    75.
    Ante VM, Bina XR, Howard MF, Sayeed S, Taylor DL, Bina JE. 2015. Vibrio cholerae leuO transcription is positively regulated by ToxR and contributes to bile resistance. J Bacteriol 197:3499–3510.
    76.
    Provenzano D, Lauriano CM, Klose KE. 2001. Characterization of the role of the ToxR-modulated outer membrane porins OmpU and OmpT in Vibrio cholerae virulence. J Bacteriol 183:3652–3662.
    77.
    Bina JE, Mekalanos JJ. 2001. Vibrio cholerae tolC is required for bile resistance and colonization. Infect Immun 69:4681–4685.
    78.
    Chatterjee A, Chaudhuri S, Saha G, Gupta S, Chowdhury R. 2004. Effect of bile on the cell surface permeability barrier and efflux system of Vibrio cholerae. J Bacteriol 186:6809–6814.
    79.
    Cerda-Maira FA, Kovacikova G, Jude BA, Skorupski K, Taylor RK. 2013. Characterization of BreR interaction with the bile response promoters breAB and breR in Vibrio cholerae. J Bacteriol 195:307–317.
    80.
    Cerda-Maira FA, Ringelberg CS, Taylor RK. 2008. The bile response repressor BreR regulates expression of the Vibrio cholerae breAB efflux system operon. J Bacteriol 190:7441–7452.
    81.
    Bina JE, Provenzano D, Wang C, Bina XR, Mekalanos JJ. 2006. Characterization of the Vibrio cholerae vexAB and vexCD efflux systems. Arch Microbiol 186:171–181.
    82.
    Herrera CM, Crofts AA, Henderson JC, Pingali SC, Davies BW, Trent MS. 2014. The Vibrio cholerae VprA-VprB two-component system controls virulence through endotoxin modification. mBio 5:e02283-14.
    83.
    Gupta P, Sarkar S, Das B, Bhattacharjee S, Tribedi P. 16 September 2015. Biofilm, pathogenesis and prevention—a journey to break the wall: a review. Arch Microbiol doi:
    84.
    Hung DT, Zhu J, Sturtevant D, Mekalanos JJ. 2006. Bile acids stimulate biofilm formation in Vibrio cholerae. Mol Microbiol 59:193–201.
    85.
    Koestler BJ, Waters CM. 2014. Bile acids and bicarbonate inversely regulate intracellular cyclic di-GMP in Vibrio cholerae. Infect Immun 82:3002–3014.
    86.
    Koestler BJ, Waters CM. 2014. Intestinal GPS: bile and bicarbonate control cyclic di-GMP to provide Vibrio cholerae spatial cues within the small intestine. Gut Microbes 5:775–780.
    87.
    Hay AJ, Zhu J. 2015. Host intestinal signal-promoted biofilm dispersal induces Vibrio cholerae colonization. Infect Immun 83:317–323.
    88.
    Gupta S, Chowdhury R. 1997. Bile affects production of virulence factors and motility of Vibrio cholerae. Infect Immun 65:1131–1134.
    89.
    Schuhmacher DA, Klose KE. 1999. Environmental signals modulate ToxT-dependent virulence factor expression in Vibrio cholerae. J Bacteriol 181:1508–1514.
    90.
    Hung DT, Mekalanos JJ. 2005. Bile acids induce cholera toxin expression in Vibrio cholerae in a ToxT-independent manner. Proc Natl Acad Sci U S A 102:3028–3033.
    91.
    Yang M, Liu Z, Hughes C, Stern AM, Wang H, Zhong Z, Kan B, Fenical W, Zhu J. 2013. Bile salt-induced intermolecular disulfide bond formation activates Vibrio cholerae virulence. Proc Natl Acad Sci U S A 110:2348–2353.
    92.
    Chatterjee A, Dutta PK, Chowdhury R. 2007. Effect of fatty acids and cholesterol present in bile on expression of virulence factors and motility of Vibrio cholerae. Infect Immun 75:1946–1953.
    93.
    Plecha SC, Withey JH. 2015. Mechanism for inhibition of Vibrio cholerae ToxT activity by the unsaturated fatty acid components of bile. J Bacteriol 197:1716–1725.
    94.
    Alam A, Tam V, Hamilton E, Dziejman M. 2010. vttRA and vttRB encode ToxR family proteins that mediate bile-induced expression of type three secretion system genes in a non-O1/non-O139 Vibrio cholerae strain. Infect Immun 78:2554–2570.
    95.
    Alam A, Miller KA, Chaand M, Butler JS, Dziejman M. 2011. Identification of Vibrio cholerae type III secretion system effector proteins. Infect Immun 79:1728–1740.
    96.
    Miller KA, Hamilton E, Dziejman M. 2012. The Vibrio cholerae trh gene is coordinately regulated in vitro with type III secretion system genes by VttR(A)/VttR(B) but does not contribute to Caco2-BBE cell cytotoxicity. Infect Immun 80:4444–4455.
    97.
    Bachmann V, Kostiuk B, Unterweger D, Diaz-Satizabal L, Ogg S, Pukatzki S. 2015. Bile salts modulate the mucin-activated type VI secretion system of pandemic Vibrio cholerae. PLoS Negl Trop Dis 9:e0004031.
    98.
    Russell AB, Peterson SB, Mougous JD. 2014. Type VI secretion system effectors: poisons with a purpose. Nat Rev Microbiol 12:137–148.
    99.
    Matsuo T, Nakamura K, Kodama T, Mikami T, Hiyoshi H, Tsuchiya T, Ogawa W, Kuroda T. 2013. Characterization of all RND-type multidrug efflux transporters in Vibrio parahaemolyticus. Microbiologyopen 2:725–742.
    100.
    Matsuo T, Ogawa W, Tsuchiya T, Kuroda T. 2014. Overexpression of vmeTUV encoding a multidrug efflux transporter of Vibrio parahaemolyticus causes bile acid resistance. Gene 541:19–25.
    101.
    Lee S, Yeom JH, Seo S, Lee M, Kim S, Bae J, Lee K, Hwang J. 2015. Functional analysis of Vibrio vulnificus RND efflux pumps homologous to Vibrio cholerae VexAB and VexCD, and to Escherichia coli AcrAB. J Microbiol 53:256–261.
    102.
    Chen WL, Oliver JD, Wong HC. 2010. Adaptation of Vibrio vulnificus and an rpoS mutant to bile salts. Int J Food Microbiol 140:232–238.
    103.
    Wong HC, Liu SH. 2006. Susceptibility of the heat-, acid-, and bile-adapted Vibrio vulnificus to lethal low-salinity stress. J Food Prot 69:2924–2928.
    104.
    Livny J, Zhou X, Mandlik A, Hubbard T, Davis BM, Waldor MK. 2014. Comparative RNA-Seq based dissection of the regulatory networks and environmental stimuli underlying Vibrio parahaemolyticus gene expression during infection. Nucleic Acids Res 42:12212–12223.
    105.
    Gotoh K, Kodama T, Hiyoshi H, Izutsu K, Park KS, Dryselius R, Akeda Y, Honda T, Iida T. 2010. Bile acid-induced virulence gene expression of Vibrio parahaemolyticus reveals a novel therapeutic potential for bile acid sequestrants. PLoS One 5:e13365.
    106.
    Osawa R, Yamai S. 1996. Production of thermostable direct hemolysin by Vibrio parahaemolyticus enhanced by conjugated bile acids. Appl Environ Microbiol 62:3023–3025.
    107.
    Fabrega A, Vila J. 2013. Salmonella enterica serovar Typhimurium skills to succeed in the host: virulence and regulation. Clin Microbiol Rev 26:308–341.
    108.
    de Jong HK, Parry CM, van der Poll T, Wiersinga WJ. 2012. Host-pathogen interaction in invasive salmonellosis. PLoS Pathog 8:e1002933.
    109.
    Beltran P, Musser JM, Helmuth R, Farmer JJ, III, Frerichs WM, Wachsmuth IK, Ferris K, McWhorter AC, Wells JG, Cravioto A. 1988. Toward a population genetic analysis of Salmonella: genetic diversity and relationships among strains of serotypes S. choleraesuis, S. derby, S. dublin, S. enteritidis, S. heidelberg, S. infantis, S. newport, and S. typhimurium. Proc Natl Acad Sci U S A 85:7753–7757.
    110.
    Fuentes JA, Jofre MR, Villagra NA, Mora GC. 2009. RpoS- and Crp-dependent transcriptional control of Salmonella Typhi taiA and hlyE genes: role of environmental conditions. Res Microbiol 160:800–808.
    111.
    Vernikos GS, Parkhill J. 2006. Interpolated variable order motifs for identification of horizontally acquired DNA: revisiting the Salmonella pathogenicity islands. Bioinformatics 22:2196–2203.
    112.
    Zhang H, Zhou Y, Bao H, Liu HW. 2006. Vi antigen biosynthesis in Salmonella Typhi: characterization of UDP-N-acetylglucosamine C-6 dehydrogenase (TviB) and UDP-N-acetylglucosaminuronic acid C-4 epimerase (TviC). Biochemistry 45:8163–8173.
    113.
    Srikanth CV, Mercado-Lubo R, Hallstrom K, McCormick BA. 2011. Salmonella effector proteins and host-cell responses. Cell Mol Life Sci 68:3687–3697.
    114.
    Deng L, Song J, Gao X, Wang J, Yu H, Chen X, Varki N, Naito-Matsui Y, Galan JE, Varki A. 2014. Host adaptation of a bacterial toxin from the human pathogen Salmonella Typhi. Cell 159:1290–1299.
    115.
    Song J, Gao X, Galan JE. 2013. Structure and function of the Salmonella Typhi chimaeric A(2)B(5) typhoid toxin. Nature 499:350–354.
    116.
    Atlas RM. 1996. Handbook of microbiological media, 2nd ed. CRC Press, Boca Raton, FL.
    117.
    Alvarez-Ordonez A, Begley M, Prieto M, Messens W, Lopez M, Bernardo A, Hill C. 2011. Salmonella spp. survival strategies within the host gastrointestinal tract. Microbiology 157:3268–3281.
    118.
    Nishino K, Latifi T, Groisman EA. 2006. Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium. Mol Microbiol 59:126–141.
    119.
    Nikaido E, Yamaguchi A, Nishino K. 2008. AcrAB multidrug efflux pump regulation in Salmonella enterica serovar Typhimurium by RamA in response to environmental signals. J Biol Chem 283:24245–24253.
    120.
    Martins A, Amaral L. 2012. Screening for efflux pump systems of bacteria by the new acridine orange agar method. In Vivo 26:203–206.
    121.
    Buckley AM, Webber MA, Cooles S, Randall LP, La Ragione RM, Woodward MJ, Piddock LJ. 2006. The AcrAB-TolC efflux system of Salmonella enterica serovar Typhimurium plays a role in pathogenesis. Cell Microbiol 8:847–856.
    122.
    Bailey AM, Ivens A, Kingsley R, Cottell JL, Wain J, Piddock LJ. 2010. RamA, a member of the AraC/XylS family, influences both virulence and efflux in Salmonella enterica serovar Typhimurium. J Bacteriol 192:1607–1616.
    123.
    Baucheron S, Nishino K, Monchaux I, Canepa S, Maurel MC, Coste F, Roussel A, Cloeckaert A, Giraud E. 2014. Bile-mediated activation of the acrAB and tolC multidrug efflux genes occurs mainly through transcriptional derepression of ramA in Salmonella enterica serovar Typhimurium. J Antimicrob Chemother 69:2400–2406.
    124.
    van Velkinburgh JC, Gunn JS. 1999. PhoP-PhoQ-regulated loci are required for enhanced bile resistance in Salmonella spp. Infect Immun 67:1614–1622.
    125.
    Lahiri A, Ananthalakshmi TK, Nagarajan AG, Ray S, Chakravortty D. 2011. TolA mediates the differential detergent resistance pattern between the Salmonella enterica subsp. enterica serovars Typhi and Typhimurium. Microbiology 157:1402–1415.
    126.
    Prouty AM, Brodsky IE, Falkow S, Gunn JS. 2004. Bile-salt-mediated induction of antimicrobial and bile resistance in Salmonella typhimurium. Microbiology 150:775–783.
    127.
    Dalebroux ZD, Miller SI. 2014. Salmonellae PhoPQ regulation of the outer membrane to resist innate immunity. Curr Opin Microbiol 17:106–113.
    128.
    Antunes LC, Wang M, Andersen SK, Ferreira RB, Kappelhoff R, Han J, Borchers CH, Finlay BB. 2012. Repression of Salmonella enterica phoP expression by small molecules from physiological bile. J Bacteriol 194:2286–2296.
    129.
    Crawford RW, Keestra AM, Winter SE, Xavier MN, Tsolis RM, Tolstikov V, Baumler AJ. 2012. Very long O-antigen chains enhance fitness during Salmonella-induced colitis by increasing bile resistance. PLoS Pathog 8:e1002918.
    130.
    Wilson RP, Raffatellu M, Chessa D, Winter SE, Tukel C, Baumler AJ. 2008. The Vi-capsule prevents Toll-like receptor 4 recognition of Salmonella. Cell Microbiol 10:876–890.
    131.
    Tran QT, Gomez G, Khare S, Lawhon SD, Raffatellu M, Baumler AJ, Ajithdoss D, Dhavala S, Adams LG. 2010. The Salmonella enterica serotype Typhi Vi capsular antigen is expressed after the bacterium enters the ileal mucosa. Infect Immun 78:527–535.
    132.
    Prieto AI, Ramos-Morales F, Casadesus J. 2004. Bile-induced DNA damage in Salmonella enterica. Genetics 168:1787–1794.
    133.
    Prieto AI, Ramos-Morales F, Casadesus J. 2006. Repair of DNA damage induced by bile salts in Salmonella enterica. Genetics 174:575–584.
    134.
    Scanu T, Spaapen RM, Bakker JM, Pratap CB, Wu LE, Hofland I, Broeks A, Shukla VK, Kumar M, Janssen H, Song JY, Neefjes-Borst EA, te Riele H, Holden DW, Nath G, Neefjes J. 2015. Salmonella manipulation of host signaling pathways provokes cellular transformation associated with gallbladder carcinoma. Cell Host Microbe 17:763–774.
    135.
    Faherty CS, Maurelli AT. 2008. Staying alive: bacterial inhibition of apoptosis during infection. Trends Microbiol 16:173–180.
    136.
    Prouty AM, Gunn JS. 2000. Salmonella enterica serovar Typhimurium invasion is repressed in the presence of bile. Infect Immun 68:6763–6769.
    137.
    Prouty AM, Brodsky IE, Manos J, Belas R, Falkow S, Gunn JS. 2004. Transcriptional regulation of Salmonella enterica serovar Typhimurium genes by bile. FEMS Immunol Med Microbiol 41:177–185.
    138.
    Takeuchi A. 1967. Electron microscope studies of experimental Salmonella infection. I. Penetration into the intestinal epithelium by Salmonella typhimurium. Am J Pathol 50:109–136.
    139.
    Jones BD, Ghori N, Falkow S. 1994. Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer's patches. J Exp Med 180:15–23.
    140.
    Kaniga K, Trollinger D, Galan JE. 1995. Identification of two targets of the type III protein secretion system encoded by the inv and spa loci of Salmonella typhimurium that have homology to the Shigella IpaD and IpaA proteins. J Bacteriol 177:7078–7085.
    141.
    Wang Y, Nordhues BA, Zhong D, De Guzman RN. 2010. NMR characterization of the interaction of the Salmonella type III secretion system protein SipD and bile salts. Biochemistry 49:4220–4226.
    142.
    Gonzalez-Escobedo G, Marshall JM, Gunn JS. 2011. Chronic and acute infection of the gall bladder by Salmonella Typhi: understanding the carrier state. Nat Rev Microbiol 9:9–14.
    143.
    Soper GA. 1939. The curious career of Typhoid Mary. Bull N Y Acad Med 15:698–712.
    144.
    Prouty AM, Schwesinger WH, Gunn JS. 2002. Biofilm formation and interaction with the surfaces of gallstones by Salmonella spp. Infect Immun 70:2640–2649.
    145.
    Marshall JM, Flechtner AD, La Perle KM, Gunn JS. 2014. Visualization of extracellular matrix components within sectioned Salmonella biofilms on the surface of human gallstones. PLoS One 9:e89243.
    146.
    Kararli TT. 1995. Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharm Drug Dispos 16:351–380.
    147.
    Silva J, Leite D, Fernandes M, Mena C, Gibbs PA, Teixeira P. 2011. Campylobacter spp. as a foodborne pathogen: a review. Front Microbiol 2:200.
    148.
    Crushell E, Harty S, Sharif F, Bourke B. 2004. Enteric Campylobacter: purging its secrets? Pediatr Res 55:3–12.
    149.
    Young KT, Davis LM, Dirita VJ. 2007. Campylobacter jejuni: molecular biology and pathogenesis. Nat Rev Microbiol 5:665–679.
    150.
    Wassenaar TM, Blaser MJ. 1999. Pathophysiology of Campylobacter jejuni infections of humans. Microbes Infect 1:1023–1033.
    151.
    Platts-Mills JA, Kosek M. 2014. Update on the burden of Campylobacter in developing countries. Curr Opin Infect Dis 27:444–450.
    152.
    Okoli AS, Wadstrom T, Mendz GL. 2007. MiniReview: bioinformatic study of bile responses in Campylobacterales. FEMS Immunol Med Microbiol 49:101–123.
    153.
    Lin J, Martinez A. 2006. Effect of efflux pump inhibitors on bile resistance and in vivo colonization of Campylobacter jejuni. J Antimicrob Chemother 58:966–972.
    154.
    Lin J, Sahin O, Michel LO, Zhang Q. 2003. Critical role of multidrug efflux pump CmeABC in bile resistance and in vivo colonization of Campylobacter jejuni. Infect Immun 71:4250–4259.
    155.
    Lin J, Akiba M, Sahin O, Zhang Q. 2005. CmeR functions as a transcriptional repressor for the multidrug efflux pump CmeABC in Campylobacter jejuni. Antimicrob Agents Chemother 49:1067–1075.
    156.
    Mavri A, Smole Mozina S. 2013. Resistance to bile salts and sodium deoxycholate in macrolide- and fluoroquinolone-susceptible and resistant Campylobacter jejuni and Campylobacter coli strains. Microb Drug Resist 19:168–174.
    157.
    Akiba M, Lin J, Barton YW, Zhang Q. 2006. Interaction of CmeABC and CmeDEF in conferring antimicrobial resistance and maintaining cell viability in Campylobacter jejuni. J Antimicrob Chemother 57:52–60.
    158.
    Gunn JS. 2000. Mechanisms of bacterial resistance and response to bile. Microbes Infect 2:907–913.
    159.
    Raphael BH, Pereira S, Flom GA, Zhang Q, Ketley JM, Konkel ME. 2005. The Campylobacter jejuni response regulator, CbrR, modulates sodium deoxycholate resistance and chicken colonization. J Bacteriol 187:3662–3670.
    160.
    Konkel ME, Klena JD, Rivera-Amill V, Monteville MR, Biswas D, Raphael B, Mickelson J. 2004. Secretion of virulence proteins from Campylobacter jejuni is dependent on a functional flagellar export apparatus. J Bacteriol 186:3296–3303.
    161.
    Christensen JE, Pacheco SA, Konkel ME. 2009. Identification of a Campylobacter jejuni-secreted protein required for maximal invasion of host cells. Mol Microbiol 73:650–662.
    162.
    Eucker TP, Konkel ME. 2012. The cooperative action of bacterial fibronectin-binding proteins and secreted proteins promote maximal Campylobacter jejuni invasion of host cells by stimulating membrane ruffling. Cell Microbiol 14:226–238.
    163.
    Konkel ME, Kim BJ, Rivera-Amill V, Garvis SG. 1999. Bacterial secreted proteins are required for the internalization of Campylobacter jejuni into cultured mammalian cells. Mol Microbiol 32:691–701.
    164.
    Rivera-Amill V, Kim BJ, Seshu J, Konkel ME. 2001. Secretion of the virulence-associated Campylobacter invasion antigens from Campylobacter jejuni requires a stimulatory signal. J Infect Dis 183:1607–1616.
    165.
    Svensson SL, Pryjma M, Gaynor EC. 2014. Flagella-mediated adhesion and extracellular DNA release contribute to biofilm formation and stress tolerance of Campylobacter jejuni. PLoS One 9:e106063.
    166.
    Fox EM, Raftery M, Goodchild A, Mendz GL. 2007. Campylobacter jejuni response to ox-bile stress. FEMS Immunol Med Microbiol 49:165–172.
    167.
    Li Z, Lou H, Ojcius DM, Sun A, Sun D, Zhao J, Lin X, Yan J. 2014. Methyl-accepting chemotaxis proteins 3 and 4 are responsible for Campylobacter jejuni chemotaxis and jejuna colonization in mice in response to sodium deoxycholate. J Med Microbiol 63:343–354.
    168.
    Malik-Kale P, Parker CT, Konkel ME. 2008. Culture of Campylobacter jejuni with sodium deoxycholate induces virulence gene expression. J Bacteriol 190:2286–2297.
    169.
    Freeman J, Bauer MP, Baines SD, Corver J, Fawley WN, Goorhuis B, Kuijper EJ, Wilcox MH. 2010. The changing epidemiology of Clostridium difficile infections. Clin Microbiol Rev 23:529–549.
    170.
    Sorg JA, Sonenshein AL. 2010. Inhibiting the initiation of Clostridium difficile spore germination using analogs of chenodeoxycholic acid, a bile acid. J Bacteriol 192:4983–4990.
    171.
    Giel JL, Sorg JA, Sonenshein AL, Zhu J. 2010. Metabolism of bile salts in mice influences spore germination in Clostridium difficile. PLoS One 5:e8740.
    172.
    Wilson KH. 1983. Efficiency of various bile salt preparations for stimulation of Clostridium difficile spore germination. J Clin Microbiol 18:1017–1019.
    173.
    Weingarden AR, Chen C, Bobr A, Yao D, Lu Y, Nelson VM, Sadowsky MJ, Khoruts A. 2014. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. Am J Physiol Gastrointest Liver Physiol 306:G310–G319.
    174.
    Gahan CG, Hill C. 2014. Listeria monocytogenes: survival and adaptation in the gastrointestinal tract. Front Cell Infect Microbiol 4:9.
    175.
    Cossart P. 2011. Illuminating the landscape of host-pathogen interactions with the bacterium Listeria monocytogenes. Proc Natl Acad Sci U S A 108:19484–19491.
    176.
    Payne A, Schmidt TB, Nanduri B, Pendarvis K, Pittman JR, Thornton JA, Grissett J, Donaldson JR. 2013. Proteomic analysis of the response of Listeria monocytogenes to bile salts under anaerobic conditions. J Med Microbiol 62:25–35.
    177.
    Quillin SJ, Schwartz KT, Leber JH. 2011. The novel Listeria monocytogenes bile sensor BrtA controls expression of the cholic acid efflux pump MdrT. Mol Microbiol 81:129–142.
    178.
    Dussurget O, Cabanes D, Dehoux P, Lecuit M, Buchrieser C, Glaser P, Cossart P, European Listeria Genome Consortium. 2002. Listeria monocytogenes bile salt hydrolase is a PrfA-regulated virulence factor involved in the intestinal and hepatic phases of listeriosis. Mol Microbiol 45:1095–1106.
    179.
    van der Veen S, Abee T. 2011. Contribution of Listeria monocytogenes RecA to acid and bile survival and invasion of human intestinal Caco-2 cells. Int J Med Microbiol 301:334–340.
    180.
    White SJ, McClung DM, Wilson JG, Roberts BN, Donaldson JR. 2015. Influence of pH on bile sensitivity amongst various strains of Listeria monocytogenes under aerobic and anaerobic conditions. J Med Microbiol 64:1287–1296.

    Author Bios

    Jeticia R. Sistrunk
    Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Jeticia R. Sistrunk received her bachelor's degree in Microbiology from the University of Oklahoma in 2008. She is currently working on comparative genomics and transcriptomics of enterotoxigenic Escherichia coli isolates in Dr. David A. Rasko's laboratory for her Ph.D. in Molecular Microbiology and Immunology from the University of Maryland School of Medicine.
    Kourtney P. Nickerson
    Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
    Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
    Kourtney P. Nickerson received her Ph.D. in Molecular Medicine from the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University in 2014. She is currently a postdoctoral scientist at Massachusetts General Hospital, conducting research at the Mucosal Immunology and Biology Research Center in the laboratories of Dr. Christina S. Faherty and Dr. Alessio Fasano. Her research focuses on host-pathogen interactions in Shigella flexneri and Salmonella Typhi.
    Rachael B. Chanin
    Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
    Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
    Rachael B. Chanin received her bachelor's degree in psychology from Brandeis University in 2010. She became a research technician at the Mucosal Immunology and Biology Research Center at Massachusetts General Hospital in 2014 and is currently researching the early infection process of Shigella flexneri. In the fall of 2016, she will begin a Ph.D. program at the UT Southwestern Medical Center in the Division of Basic Sciences.
    David A. Rasko
    Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
    David A. Rasko is an Associate Professor at the Institute for Genome Sciences, University of Maryland School of Medicine. His research focuses on utilizing comparative genomics of closely related isolates to examine pathogen evolution, with a particular interest in Acinetobacter baumannii, Escherichia coli, and Shigella. Dr. Rasko earned a Ph.D. in Medical Microbiology and Immunology at the University of Alberta, Canada, in 2000. He did a postdoctoral fellowship at the University of Maryland School of Medicine and has served as both a GenBank Biologist at the National Center for Biotechnology Information (NCBI) and a staff scientist at the Institute for Genomic Research (TIGR). Following a Research Assistant Professor position at the University of Texas Southwestern Medical Center at Dallas, Dr. Rasko became an Assistant Professor at the University of Maryland School of Medicine in 2008 and was promoted to Associate Professor in 2013.
    Christina S. Faherty [email protected]
    Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
    Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
    Christina S. Faherty is an Assistant Professor at the Mucosal Immunology and Biology Research Center at Massachusetts General Hospital with an academic appointment at Harvard Medical School. Her research focuses on host-pathogen interactions in enteric bacterial pathogens, and she is specifically interested in how Shigella utilizes host signals to alter virulence gene expression prior to invasion of colonic epithelial cells. Dr. Faherty received her Ph.D. in Infectious Diseases at the Uniformed Services University of the Health Sciences in Bethesda, MD, in 2009. She did her postdoctoral work at the Center for Vaccine Development, University of Maryland School of Medicine, and became an Assistant Professor at Massachusetts General Hospital/Harvard Medical School in 2013.

    Information & Contributors

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    Published In

    Clinical Microbiology Reviews
    Volume 29Number 4October 2016
    Pages: 819 - 836

    History

    Published online: 27 July 2016

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    Contributors

    Authors

    Jeticia R. Sistrunk
    Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Kourtney P. Nickerson
    Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
    Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
    Rachael B. Chanin
    Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
    Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
    David A. Rasko
    Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Christina S. Faherty [email protected]
    Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, USA
    Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA

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