Emergence of a Potent Multidrug Efflux Pump Variant That Enhances Campylobacter Resistance to Multiple Antibiotics
ABSTRACT
INTRODUCTION
RESULTS
Identification of a unique CmeABC variant associated with resistance to florfenicol and other antimicrobials.
Strain | Description | MIC (mg/liter)a of: | ||||
---|---|---|---|---|---|---|
FFC | CHL | CIP | ERY | TET | ||
DH161 | C. coli from duck, isolated in 2009 | 16 | 256 | 256 | 4 | 512 |
NCTC 11168 | C. jejuni reference strain | 0.5 | 1 | 0.125 | 1 | 1 |
NT161 | Transformant of NCTC 11168 carrying RE-cmeABC from DH161 | 16 | 16 | 1 | 4 | 4 |
NT161-aphA-3 | NT161cmeABC::aphA-3 | 0.25 | 0.25 | <0.03 | <0.125 | <0.06 |
11168-V1 | NCTC 11168 with RE-cmeABC of NT161 and its promoter sequence | 16 | 16 | 1 | 4 | 4 |
11168-V2 | NCTC 11168 with RE-cmeABC of NT161 but original promoter of cmeABC in NCTC 11168 | 4 | 4 | 0.5 | 2 | 2 |
81–176 | C. jejuni reference strain | 0.5 | 2 | 0.125 | 0.25 | - |
81–176-V | 81-176 with RE-cmeABC of DH161 | 32 | >64 | 1 | 512 | - |
11168-C257T | NCTC 11168 with C257T mutation in gyrA | 0.5 | 1 | 16 | 1 | 1 |
NT161-C257T | NT161 with C257T mutation in gyrA | 16 | 16 | 256 | 4 | 4 |
Functional confirmation of RE-CmeABC.
Contribution of RE-CmeABC to extremely high-level ciprofloxacin resistance in Campylobacter isolates.
RE-CmeABC increases the frequencies of emergence of fluoroquinolone-resistant Campylobacter mutants.
Structural modeling of CmeB suggests enhanced drug binding by the transporter.
Rising prevalence of RE-CmeABC in C. jejuni isolates.
Yr and location of isolation | Host | (%) no. of positive isolates/total no. of isolates | (%) no. of positive isolates/total no. of isolates | |
---|---|---|---|---|
C. jejuni | C. coli | |||
2012 | ||||
Guangdong | Chicken | (8.9) 11/124 | (20.6) 7/34 | (4.4) 4/90 |
Swine | (1.0) 2/191 | (0.0) 0/1 | (1.1) 2/190 | |
Ningxia | Chicken | (15.2) 5/33 | (31.3) 5/16 | (0.0) 0/17 |
Swine | (1.4) 3/208 | (1.4) 3/208 | ||
Shandong | Swine | (2.8) 2/71 | (2.8) 2/71 | |
Shanghai | Chicken | (20.4) 32/157 | (36.2) 25/69 | (8.0) 7/88 |
Total | (7.0) 55/784 | (30.8) 37/120 | (2.7) 18/664 | |
2013 | ||||
Guangdong | Chicken | (17.0) 18/106 | (66.7) 10/15 | (8.8) 8/91 |
Swine | (3.7) 2/54 | (100.0) 1/1 | (1.9) 1/53 | |
Ningxia | Chicken | (0.5) 1/196 | (0.7) 1/144 | (0.0) 0/52 |
Swine | (0.0) 0/24 | (0.0) 0/2 | (0.0) 0/22 | |
Shandong | Chicken | (25.0) 18/72 | (19.4) 13/67 | (100.0) 5/5 |
Shanghai | Chicken | (9.8) 13/132 | (40.7) 11/27 | (1.9) 2/105 |
Henan | Chicken | (80.0) 8/10 | (100.0) 8/8 | (0.0) 0/2 |
Swine | (0.0) 0/17 | (0.0) 0/17 | ||
Total | (9.8) 60/611 | (16.7) 44/264 | (4.6) 16/347 | |
2014 | ||||
Guangdong | Chicken | (15.6) 21/135 | (81.3) 13/16 | (6.7) 8/119 |
Ningxia | Chicken | (6.7) 4/60 | (8.1) 3/37 | (4.3) 1/23 |
Swine | (30.8) 8/26 | (66.7) 4/6 | (20.0) 4/20 | |
Shandong | Chicken | (0.0)0/164 | (0.0) 0/1 | (0.0) 0/163 |
Shanghai | Chicken | (18.2) 14/77 | (56.0) 14/25 | (0.0) 0/52 |
Swine | (0.0) 0/52 | (0.0) 0/52 | ||
Henan | Chicken | (93.7) 74/79 | (98.7) 74/75 | (0.0) 0/4 |
Swine | (0.0) 0/14 | (0.0) 0/14 | ||
Total | (19.9) 121/607 | (67.5) 108/160 | (2.9) 13/447 | |
All | ||||
Chicken | (16.3) 219/1,345 | (34.4) 184/534 | (4.3) 35/811 | |
Swine | (2.6) 17/657 | (50.0) 5/10 | (1.9) 12/647 | |
Total | (11.8) 236/2,002 | (34.7) 189/544 | (3.2) 47/1,458 |
Molecular typing and phylogenetic analysis of RE-cmeABC-carrying C. jejuni and C. coli isolates.
DISCUSSION
MATERIALS AND METHODS
Campylobacter strains and antimicrobial susceptibility testing.
Detection of florfenicol and fluoroquinolone resistance determinants.
Natural transformation.
Random transposon mutagenesis.
Whole-genome sequencing.
Introduction of RE-cmeABC into C. jejuni 81-176.
Selection of the C257T mutation in the gyrA gene.
Determining frequencies of emergence of fluoroquinolone-resistant mutants.
Sequence analysis and structure prediction of CmeB.
Real-time RT-PCR analysis of cmeABC transcription.
Ciprofloxacin accumulation assay.
Detection of RE-cmeABC in Campylobacter isolates.
PFGE.
Accession number.
ACKNOWLEDGMENTS
Footnote
Supplemental Material
REFERENCES
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