Free access
1 October 2014

Microbiology, Genomics, and Clinical Significance of the Pseudomonas fluorescens Species Complex, an Unappreciated Colonizer of Humans


Pseudomonas fluorescens is not generally considered a bacterial pathogen in humans; however, multiple culture-based and culture-independent studies have identified it at low levels in the indigenous microbiota of various body sites. With recent advances in comparative genomics, many isolates originally identified as the “species” P. fluorescens are now being reclassified as novel Pseudomonas species within the P. fluorescens “species complex.” Although most widely studied for its role in the soil and the rhizosphere, P. fluorescens possesses a number of functional traits that provide it with the capability to grow and thrive in mammalian hosts. While significantly less virulent than P. aeruginosa, P. fluorescens can cause bacteremia in humans, with most reported cases being attributable either to transfusion of contaminated blood products or to use of contaminated equipment associated with intravenous infusions. Although not suspected of being an etiologic agent of pulmonary disease, there are a number of reports identifying it in respiratory samples. There is also an intriguing association between P. fluorescens and human disease, in that approximately 50% of Crohn's disease patients develop serum antibodies to P. fluorescens. Altogether, these reports are beginning to highlight a far more common, intriguing, and potentially complex association between humans and P. fluorescens during health and disease.


Over the past 15 years, the application of culture-independent methods for microbial identification has revealed a previously unappreciated complexity within human-microbe interactions. One interesting feature is that a number of these studies have identified the bacterium Pseudomonas fluorescens as a low-abundance member of the indigenous microbiota of various body sites, including the mouth, stomach, and lungs (1 5). P. fluorescens has generally been considered nonpathogenic for humans, an assessment dating back to its earliest descriptions, by A. Baader and C. Garre, in Über Antagonisten unter den Bacterien (1887) (6):
The bacillus [P. fluorescens] itself is not pathogenic. A culture applied to animals subcutaneously or injected into the peritoneum does not elicit a reaction. Even when introduced many times into fresh wounds it does not irritate healing by primary intention. Also, ingestion of cultures caused no harm to my stomach or intestines.
However, while far less virulent than P. aeruginosa, P. fluorescens can cause acute infections (opportunistic) in humans and has been reported in clinical samples from the mouth, stomach, and lungs (Table 1). The most common site of P. fluorescens infection is the bloodstream. Most reported cases have been iatrogenic, with bacteremia attributable either to transfusion of contaminated blood products (7 12) or to use of contaminated equipment associated with intravenous infusions (13 17). While not suspected of being an etiologic agent of pulmonary disease, we recently reported that P. fluorescens is routinely cultured at a low frequency from clinically indicated respiratory samples (3) (Table 2). Perhaps the most intriguing “association” between P. fluorescens and human disease is that approximately 50% of Crohn's disease patients develop serum antibodies to the I2 antigen encoded by P. fluorescens, and in some studies, this seroreactivity has correlated with the success of therapies aimed at the microbiome rather than the immune system (18 22). Altogether, these reports and others are beginning to highlight a far more common, and potentially complex, interaction between humans and P. fluorescens during health and disease.
TABLE 1 Reported P. fluorescens infections
Organ or tissueNo. of reported cases a Reference(s)
Blood1108 17, 183 189
Bone2213, 214
Cerebrospinal fluid1215
Eye3216 218
Lung3195 198
Skin/wound5190, 191, 194
Urinary tract5192 194
Total number of cases reported in the medical literature. MEDLINE searches were performed with the search term “Pseudomonas fluorescens” and filtered for human studies, with no date or language restrictions. All abstracts were read and reviewed by us, and relevant references were read in their entirety.
TABLE 2 P. fluorescens isolates cultured over an 11-year period by the University of Michigan Hospital Microbiology Lab a
Parameter b % of isolates
Culture method
    Cultured using routine laboratory protocols59.50
    Cultured using modified CF protocols40.10
Sample type
    Sputum samples53.70
    Throat swabs21.10
    Bronchoscopically obtained samples (BAL fluids or brushings)13.20
    Other (tracheal aspirates, sinus aspirates)12.00
Underlying disease/cause
    Other chronic airway disease (COPD, asthma, non-CF bronchiectasis)16.10
    Lung transplantation7.40
    Acute pneumonia (in chronically immunosuppressed patient or hospital acquired)9.90
    Acute pneumonia (not in chronically immunosuppressed patient or hospital acquired)1.60
    Other (chronic tracheostomy, sinusitis, acute respiratory distress syndrome, bone marrow transplantation)26.20
Cocultured bacteria
    “Oral flora” species85.10
    Pseudomonas aeruginosa25.60
    Staphylococcus aureus15.70
    Stenotrophomonas maltophilia11.60
The data show a breakdown of 242 P. fluorescens isolates cultured between 1 January 2002 and 13 December 2012 (3).
CF, cystic fibrosis; BAL, bronchoalveolar lavage.
The extremely versatile metabolic capabilities of P. fluorescens impart this bacterium with the ability to persist in a wide range of environments beyond mammalian hosts (Fig. 1), including soil, the rhizospheres and surfaces of plants, nonsterile pharmaceuticals, showerheads, and even indoor wall surfaces (23, 24). P. fluorescens has been studied most widely as an environmental microbe, most notably for its role in promoting plant health via a number of encoded antimicrobial mechanisms (25 38). However, P. fluorescens also possesses a number of functional traits that provide it with the capability to grow and thrive in mammalian hosts, including production of bioactive secondary metabolites (26 30, 33, 39 42), siderophores (43 45), and a type III secretion system (46 51), the ability to form biofilms (20, 52 56), and the plasticity of some strains to adapt to growth at higher temperature (53, 57 59).
FIG 1 Functional range and environmental niches of the Pseudomonas genus, highlighting the broad distribution of the P. fluorescens species complex. Members of the P. fluorescens species complex are successful colonizers in a wide range of environments and habitats due to diverse functional abilities. (Reprinted from reference 208 with permission of John Wiley and Sons [copyright 2011 Federation of European Microbiological Societies].)
With recent rapid advancements in taxonomy and comparative genomics, many Pseudomonas isolates originally identified as the “species” P. fluorescens are now being reclassified as novel Pseudomonas species within the P. fluorescens “species complex” (23, 60, 61). There are at least 52 species within this group (Fig. 2), and they share many phenotypic characteristics (Fig. 3). Since the taxonomic reclassifications within P. fluorescens are relatively new and ongoing, and beyond the scope of this review, we use the term “P. fluorescens species complex,” or simply “P. fluorescens,” in this review for studies on any isolates within this Pseudomonas species complex (Fig. 2).
FIG 2 Species diversity within the P. fluorescens species complex. Mulet et al. generated a phylogenetic tree from 107 Pseudomonas type strains, based on concatenated analysis of the 16S rRNA, gyrB, rpoB, and rpoD genes, with Cellvibrio japonicum Ueda107 included as the outgroup (74). The bar indicates sequence divergence. (Reproduced from reference 74 with permission of John Wiley and Sons [copyright 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.]. The names of the Pseudomonas species that have been included in the P. fluorescens species complex were added to the original figure.)
FIG 3 Scanning electron micrograph of P. fluorescens. (Photo reprinted with permission of Science Source.)


The bacteria in the P. fluorescens species complex are Gram-negative, motile rods that are primarily aerobic, unable to ferment glucose, and chemoorganotrophic and grow at a pH between 4 and 8 (62) (Table 3 and Fig. 3). Isolates of P. fluorescens derived from nonmammalian samples have a permissive growth range of 4 to 32°C (62), while isolates from humans and other mammals have an elevated upper range extending to 37°C (53, 57 59). As of the end of 2013, there were 16 fully sequenced strains from the P. fluorescens species complex, and all but one originated from plant surfaces, roots, or the surrounding soil (Table 4). P. fluorescens can also be found in an antagonistic relationship with eukaryotic microbes, including oomycetes and amoeba (35, 36, 48, 51, 59, 63 65), with the latter relationship potentially reflecting conserved mechanisms that are also used with macrophages, as has been hypothesized for other bacteria (66).
TABLE 3 Characteristics of P. fluorescens complex bacteria
    Bacteria, Proteobacteria, Gammaproteobacteria, Pseudomonadales, Pseudomonadaceae, Pseudomonas
Physical characteristics
    Gram-negative, rod-shaped bacilli
    Motile via motile polar flagella
    Non-spore-forming organisms
    Produce a fluorescent pigment (pyocyanin), from which the name P. fluorescens is derived
    Produce exopolysaccharides and readily form biofilms
Growth characteristics
    Obligate aerobes but capable of using nitrate instead of oxygen as a final electron acceptor during cellular respiration
    Optimal temperatures for growth
        25–30°C for environmental isolates
        34–37°C for mammalian isolates
    Oxidase positive
    Catalase positive
    Grow well on Trypticase soy agar (TSA) and Luria agar (LA)
    Hemolytic activity on red blood cells
        No for environmental isolates
        Yes for certain mammalian isolates (e.g., strain MFN1032)
    Form small, white, convex colonies
TABLE 4 Summary of information on fully sequenced bacterial strains from the P. fluorescens species complex a
StrainIsolation sourceGenome size (Mb)% G+CYr isolated/yr sequencedGenBank accession no.Reference(s)
P. fluorescens strains
    Pf0-1Loam soil, Sherborn, MA6.4460.51988/2009NC_007492.223, 221
    SBW25Sugar beet phyllosphere, Oxfordshire, UK6.7260.51989/2009NC_01266023
    A506Pear phyllosphere, California6.0259.91994/2012NC_01791149, 222
    Q2-87Wheat rhizosphere, Washington State (same field as that for Q8r1-96)6.3760.61987/2012NZ_CM001558.149, 223
    Q8r1-96Wheat rhizosphere, Washington State (same field as that for Q2-87)6.6611996/2012NZ_CM001512.149, 224
    SS101Wheat rhizosphere, near city of Bergen op Zoom, The Netherlands6.18602003/2012NZ_CM00151349, 64
    WH6Rhizosphere of Poa sp. and Triticum aestivum at Hyslop Research Farm, Benton County, ORNANA2008/2010 (draft)NA225, 226
    F113Sugar beet rhizosphere6.8560.81992/2012NC_01683050, 158
    R124Tepui orthoquartzite sandstone cave in Guiana Shield, South America6.3NA2007/2013NZ_CM001561227
    NCIM 11764Culture supplied with potassium cyanide as the sole nitrogen source6.97591983/2012NA232, 233
P. protegens strains
    Pf-5Soil, Texas7.0763.31978/2005NC_004129.6228
    CHA0Tobacco roots, Morens, Switzerland6.8763.41983/2013NC_021237.1229, 230
P. brassicacearum subsp. brassicacearum NFM421Plant rhizosphere6.8460.8NA/2011NC_015379.1231
P. chlororaphis subsp. aureofaciens strains
    30-84Wheat rhizosphere, Kansas6.6762.9NA/2012NZ_CM00155949
    O6Soil, Utah6.9862.91996/2012NZ_CM00149049, 234
P. synxatha BG33RPeach rhizosphere, South Carolina6.359.61993/2012NZ_CM00151449, 235
NA, not available.
Like most members of the Pseudomonas genus, P. fluorescens species complex strains grow best in a rich, peptide-containing medium with a 0.1 to 1.0% (wt/vol) energy source (62). Examples of such basic media include nutrient broth/agar and tryptic soy broth/agar (62). Selective media that are deficient in iron allow for the detection of the natural fluorescence produced by these bacteria, which is enhanced due to increased production of fluorescent siderophores. King's A and B media (67), Pseudosel agar medium (BBL Microbiology Systems), and Pseudomonas agar F medium (Difco Laboratories, Detroit, MI) are all examples of pigment-enhancing media. These media also contain additional compounds, such as potassium, magnesium, and/or cetrimide, that further enable selective growth of P. fluorescens species complex bacteria. Cetrimide in particular helps to inhibit the growth of non-Pseudomonas microbial flora and allows for adequate pigment production from P. aeruginosa (68). One of the difficulties in isolation of particular species of the Pseudomonas genus is that they share many of the same phenotypic traits and grow under the same cultivation conditions. However, it is possible to use pigment production, which varies by species group, to visibly distinguish isolates from different groups. The blue-green pigment pyocyanin, readily produced by P. aeruginosa strains, is typically not produced by strains of the P. fluorescens species complex (62). Therefore, a mixed culture of P. fluorescens species complex bacteria and P. aeruginosa bacteria grown on cetrimide agar will produce blue fluorescent colonies of P. aeruginosa and nonblue fluorescent colonies of P. fluorescens complex bacteria.
Environmental isolates of P. fluorescens are readily cultivated in the laboratory by use of standard culturing techniques at a lower temperature range (5°C to 32°C), but in samples from higher temperatures or in clinical material, cultivation of P. fluorescens may be more difficult. P. fluorescens can be cultivated from environmental samples by using a simple medium with a carbon source and aerobic incubation for 24 to 48 h at 27°C to 32°C (62). However, incubation of environmental samples at temperatures of 35°C to 37°C can cause P. fluorescens to enter a viable-but-not-culturable (VBNC) state (69), complicating cultivation. During the VBNC state, bacteria are still metabolically active but are unable to undergo cellular division and replication (70). Bacteria in a VBNC state often will not grow when immediately transferred to standard culture conditions. Escherichia coli, Listeria monocytogenes, Salmonella enterica serovar Enteritidis, and Shigella dysenteriae are all examples of bacteria that can enter into a VBNC state (71). Vibrio species also undergo a switch to a VBNC state that, similar to the case of P. fluorescens, is prompted by a switch in temperature (72). The VBNC state is hypothesized to be a survival strategy that allows bacteria to persist in harsh environments (73). The ability of P. fluorescens to become VBNC could explain the phenomenon in which P. fluorescens can be found more frequently in human lung metagenomic DNA than is reported by standard hospital culture methods (3). However, some isolates of P. fluorescens from human samples have adapted well to a higher permissive temperature range than that for isolates from environmental samples. For example, we have a collection of over 30 P. fluorescens strains from cystic fibrosis patients that grow well at 37°C. Another study reported a series of P. fluorescens isolates from surface abscess, septicemia, and respiratory or urinary tract infections that were able to grow at 37°C (57). All seven were also able to grow at 4°C, often considered the lower limit of the optimal temperature range of Pseudomonas spp. (62), suggesting that these strains did not shift their temperature range but, rather, the range expanded upwards.


Taxonomy and Genomics of the Pseudomonas Genus and the P. fluorescens Species Complex

Of the many species within the Pseudomonas genus, the P. fluorescens species complex contains ∼20% (74). As of January 2014, the List of Prokaryotic Names with Standing in Nomenclature (LPSN) recognized 211 species and 18 subspecies in the Pseudomonas genus ( This reflects a 40% increase in newly defined Pseudomonas species compared to the number in 2006 (74). In the last few decades, isolates classified as P. fluorescens have undergone extensive renaming and reorganization, consistent with the high degree of genomic diversity within this species complex (75). Historically, any bacterium that was a Gram-negative, strictly aerobic, nonsporulating, motile bacillus was classified as belonging to the Pseudomonas genus (76). The name Pseudomonas derives from the Greek words for “false” (pseudes) and “single unit” (monas), so it is ironic that taxonomy within the Pseudomonas genus is undergoing reorganization in the genomic era (77). Molecular methods, including analysis of 16S rRNA gene sequences, other highly conserved “housekeeping” genes, and, more recently, full-length genomes, have accelerated the pace of taxonomic reorganization, especially within the P. fluorescens species complex (76, 78 80). Multilocus sequence typing (MLST) and multilocus sequence analysis (MLSA) utilize the concept of genetic evolution at multiple conserved genes to measure evolutionary distances between species or strains (81 83). These conserved (“housekeeping”) genes are required for the basic functions of the cell and must be found in all bacteria in the comparison (84 86). Examples of housekeeping genes used in classifying Pseudomonas species include rpoD (σ-subunit of RNA polymerase), rpoB (β-subunit of RNA polymerase), and gyrB (β-subunit of gyrase, responsible for negative supercoiling of DNA during replication) (80, 87, 88). The combination of these three housekeeping genes and the 16S rRNA gene was used to identify members of the Pseudomonas genus, create a phylogenetic tree, and divide them into different groups (74, 76) (Fig. 2). One of the key findings of these analyses is that the widest range of genomic diversity in the Pseudomonas genus is found in the P. fluorescens species complex (74) (Fig. 2).
The P. fluorescens species complex includes at least 52 separately named species, including P. poae, P. synxatha, P. tolaasii, P. brassicacearum, P. chlororaphis, and P. fluorescens (23, 60, 61). The P. fluorescens species complex can also be divided into three smaller taxonomic clades, based on 16S rRNA gene and MLST analyses (23, 49, 74, 89, 90) (Fig. 4). Silby et al. and Loper et al. have published comparative genomic analyses of three and seven bacterial strains, respectively, within the P. fluorescens species complex (23, 49). One approach to studying the level of genetic diversity between P. fluorescens strains is via the size of the pan-genome, which is the total number of genes found across all strains. While the pan-genome of P. aeruginosa is 7,824 genes, the pan-genome of P. fluorescens bacteria is much larger, at 13,782 genes. Silby et al. noted that the shared average nucleotide and amino acid identities of the three P. fluorescens genomes in their study (SBW25, Pf-5, and Pf0-1) were below those of the threshold for a “species” reported by Goris et al. (90). The study by Loper et al. included the original names of the P. fluorescens strains in the analysis but pointed out that their phylogenetic and comparative genomic analyses support the possibility that many of these species names will change in the future.
FIG 4 Phylogenetic tree of 38 Pseudomonas type strains, based on a concatenated nine-gene MLST analysis. The strains selected have full-genome sequences available through public databases. The MLST analysis was performed using nine housekeeping genes (encoding DnaE, PpsA, RecA, RpoB, GyrB, GuaA, MutL, PyrC, and AcsA), with E. coli strain K-12 used as the outgroup. A maximum likelihood tree was calculated in the online version of MAFFT (209, 210) and visualized with the software program Archaeopteryx (211). The confidence intervals after 1,000 bootstrap resamplings are indicated in red, and the branch distances are indicated in black. The bar indicates sequence divergence. P. fluorescens clade destinations are based on those proposed previously (49).
These two studies of full-length genomes confirmed the high genetic diversity within this group of bacteria. The analysis by Loper et al. (49) included a multiway BLASTp analysis to compare the seven newly sequenced P. fluorescens species complex genomes to previously annotated and sequenced genomes. An E value cutoff of 10−15 was selected to identify putative orthologs between the different strains (for DNA-DNA searches, E values of <10−10 are needed to provide evidence of homology and imply that the predicted homology would happen by chance only once in 1015 searches [91]). In the study by Silby et al. (23), a comparison of 14 Pseudomonas genomes (across multiple species) was performed all-against-all, using a reciprocal FASTA approach (30% identity over 80% of the length as the minimum similarity). While there is a “core genome” of 2,789 genes within the P. fluorescens species complex, only 20 are unique to the species complex itself within the Pseudomonas genus, and these encode proteins involved in regulation, biofilm formation, or unknown functions (49). Within each clade of the P. fluorescens species complex, the level of genetic similarity between strains is higher, with 4,188, 3,729, and 3,893 shared conserved domains between members of clades 1, 2, and 3, respectively (49).
The clade designation also offers some potential insights into functional differences between clusters of P. fluorescens, including the presence/absence and type of type III secretion system (T3SS), a molecular “needle” complex utilized by bacteria to inject bacterial proteins into host cells (49, 92). Genes for a T3SS are found only in clades 2 and 3, not clade 1. The biosynthesis gene cluster to produce hydrogen cyanide, a volatile molecule used to kill off competing bacteria, is found only in clades 1 and 2 (29, 33, 49). Genes found in every clade, such as those for the siderophore pyoverdine (93, 94), reflect functional categories that are generally preserved across the Pseudomonas genus as a whole (49). Comparative genomic analysis of P. fluorescens is in its early stages, but since there are already marked differences in the presence/absence of numerous genes between strains, this approach holds significant promise as a step in organizing the P. fluorescens species complex according to putative functional differences.

Identifying P. fluorescens in Samples by High-Throughput Sequencing

The coupling of high-throughput sequencing with the generation of 16S rRNA gene amplicon libraries from metagenomic samples has fueled the explosion in information about the microbiome and environmental microbial communities. Databases for subsequent bioinformatic analysis have continued to expand at a staggering pace. Historically, taxonomic assignment of a short read sequence from this type of analysis was limited to the family or genus level. However, as additional fully sequenced genomes become available to build validated phylogenetic trees of short read sequences, some genera can be resolved at the species level. This is turning out to be the case for some of the species in the Pseudomonas genus; the groups identified by MLST and MLSA can also be identified using the V3-V5 region of the 16S rRNA gene. As illustrated in Fig. 5, a phylogenetic tree can be generated using the16S rRNA gene sequences corresponding to the V3-V5 regions of the gene and a progressive tree alignment strategy (95 98). The bootstrap values for separating P. aeruginosa from the other Pseudomonas species are very high. While the bootstrap values are much lower for distinguishing the non-aeruginosa Pseudomonas species based on the V3-V5 region alone, the short-read, high-throughput sequencing technologies that target the V3-V5 variable region of the 16S rRNA gene can offer a first-pass analysis that discriminates between members of the P. putida and P. fluorescens/P. syringae clusters.
FIG 5 Phylogenetic tree of 38 Pseudomonas type strains, based on the V3-V5 region sequence of the 16S rRNA gene (V3 primer, positions 442 to 492; and V5 primer, positions 822 to 879 [numbered according to the E. coli 16S rRNA gene map]). The strains selected have full-genome sequences available through public databases. The V3-V5 sequence primers (212) were aligned to each genome by using DNAstar SeqBuilder software. A maximum likelihood tree was calculated in the online version of MAFFT (209, 210) and visualized with the software program Archaeopteryx (211). The confidence intervals after 1,000 bootstrap resamplings are indicated in red, and the branch distances are indicated in black. The bar indicates sequence divergence.
We have used this type of analysis, combined with other data, to demonstrate that both P. aeruginosa and P. fluorescens are prominent members of the respiratory microbiota of lung transplant recipients but that increases in their relative proportions are associated with widely divergent clinical associations (3). Multiple independent studies identified the presence of P. aeruginosa in respiratory cultures as a positive risk factor for the subsequent development of bronchiolitis obliterans syndrome (BOS) (99 101). However, in the largest published study of lung transplant subjects to date, utilizing high-throughput sequencing for microbial identification, a negative association was reported between the presence of Pseudomonas species and the diagnosis of BOS (102). In our study (3), we similarly observed high levels of Pseudomonas in lung transplant recipients (as determined by high-throughput sequencing of V3-V5 16S rRNA gene amplicon libraries). However, after applying the analysis described above and adding our Pseudomonas operational taxonomic units to the phylogenetic tree to delineate P. aeruginosa versus P. fluorescens, subjects with abundant P. aeruginosa had other clinical symptoms consistent with an acute infection, including positive P. aeruginosa bacterial cultures. In contrast, the numerous subjects with abundant P. fluorescens bacteria exhibited little evidence of acute infection, and no Pseudomonas species was detected via standard clinical laboratory bacterial culture. We alluded earlier in this review to the gap in knowledge about the factors that control culturability of P. fluorescens from clinical samples, which was underscored in our study. The surprising stark difference in culture positivity between these pseudomonads may explain the difference between prior culture-based studies (99 101) and the culture-independent study (102). Note that healthy controls in our study had very little signal for either P. aeruginosa or P. fluorescens in their bronchoalveolar lavage fluid (3). We provide this as an example of the potential power of high-throughput sequencing to provide new insights into the association of P. fluorescens with humans during health and disease.


Antibiotics and Secondary Metabolites

P. fluorescens produces a long list of secondary metabolites that allow it to successfully vie with competing microorganisms. Examples include phenazine (26 28), hydrogen cyanide (HCN) (29), 2,4-diacetylphloroglucinol (DAPG) (30, 31), rhizoxin (32 34), and pyoluteorin (35, 36). Phenazines can be produced by Gram-negative bacteria found in soil and marine environments, with Pseudomonas spp. being one of the major producers (28). Phenazines are pigmented compounds that have antitumor, antimalarial, antiparasitic, and antimicrobial activities (26). P. fluorescens produces the yellow phenazine phenazine-1-carboxylic acid (PCA) (28). Hydrogen cyanide is a volatile, colorless compound that inhibits cytochrome c oxidases and other metalloproteins in competing bacteria (33). The production of HCN by rhizosphere-inhabiting P. fluorescens suppresses plant disease (29). While it has not been studied for P. fluorescens, other Pseudomonas spp. are capable of producing HCN during human disease, such as cystic fibrosis (103). The anaerobic regulator protein ANR regulates the hcnABC gene cluster, which encodes hydrogen cyanide synthase, and, due to the oxygen sensitivity of the synthase, ensures that the genes are expressed only under low-oxygen conditions (104). DAPG production plays a significant role in the plant disease control activity of many P. fluorescens strains (30). Despite its importance, the DAPG biosynthetic cluster (phl) has been lost from all but a subset of P. fluorescens strains through evolution (31). Members of clades 1 and 2 of the P. fluorescens species complex (such as P. protegens Pf-5, P. fluorescens Q8r1-96, and P. fluorescens Q2-87) have retained the DAPG biosynthesis cluster, while all members of clade 3 do not possess this cluster (49). Intragenomic recombination and rearrangement occur frequently at this locus, such that DAPG-producing strains often have multiple versions of the phl gene cluster. In the phylogenetic lineage that retains DAPG synthesis, the gene cluster has maintained its structure, even though it has been relocated multiple times in the various P. fluorescens genomes (31). Rhizoxins are 16-membered macrocyclic lactones that interfere with microtubulin dynamics during mitosis by binding to β-tubulin (32) and that show inhibitory activity against fungi, bacteria, and tumors (33, 34). The rhizoxin-producing gene cluster in P. fluorescens is shared with another gammaproteobacterial genus, Burkholderia (105). Pyoluteorin was first isolated from a P. aeruginosa strain (106) but is now known to be produced by multiple Pseudomonas spp., including P. fluorescens (35). It has been studied in P. fluorescens strains Pf-5 and CHA0 for its antibacterial activity and ability to improve plant health (35, 36). While the activities of these secondary metabolites on human hosts remain to be determined, they benefit the survival of P. fluorescens in polymicrobial environments, opening the possibility of a role for these metabolites in survival of P. fluorescens in the human microbiome.
Other secondary metabolites produced by P. fluorescens, notably pyrrolnitrin and the pseudomonic acids, have been formulated for medical and agricultural uses. Pyrrolnitrin, a chlorinated molecule with antifungal activity, was developed into both a topical antimycotic for clinical use (39) and a fungicide for agricultural use (107). Pseudomonic acids are perhaps the most clinically important antibacterials produced by P. fluorescens. There are multiple pseudomonic acids (108), and each exhibits some level of antibacterial activity. Pseudomonic acid A has the highest activity and is the major pseudomonic acid (90%) in mupirocin, a topical antibiotic (40, 41, 109, 110). Topical mupirocin (2% concentration) is effective for treatment of superficial skin infections, such as impetigo, caused by the Gram-positive bacteria Staphylococcus spp. and Streptococcus spp. and the Gram-negative bacteria Haemophilus influenzae and Neisseria gonorrhoeae (41, 110 112). Pseudomonic acid A interacts with the amino acid binding site of isoleucyl-tRNA synthase and the respective ATP binding site, inhibiting the ability of bacteria to produce isoleucyl-tRNA synthetase (113 115). This inhibits protein synthesis primarily and RNA and bacterial cell wall synthesis to a lesser extent, possibly due to auxotrophy of amino acids that are important for these processes. The result is death of the bacterial cell. P. fluorescens is protected from pseudomonic acid because the P. fluorescens isoleucyl-tRNA target synthetase is structurally different and binds to pseudomonic acid with a much lower affinity (116). Overall, the production of pyrrolnitrin and the pseudomonic acids provides P. fluorescens with significant growth advantages in polymicrobial environments.

Siderophores and Pigments

The secretion of a fluorescent pigment, pyoverdine (formally called fluorescein), is what imparts P. fluorescens with its fluorescence properties under UV light. Pyoverdine is a siderophore (117), a high-affinity iron-chelating compound that is essential for acquisition of iron from the environment, bacterial growth, and survival (43). Pyoverdine is the main siderophore of P. fluorescens (93), but some strains of P. fluorescens contain additional secondary siderophores for iron acquisition. P. protegens CHA0, a P. fluorescens species complex strain, produces the secondary siderophore enantio-pyochelin (44), and P. fluorescens strain ATCC 17400 produces the secondary siderophores quinolobactin, pseudomonine, acinetobactin, and anguibactin (118). The last three secondary siderophores from this strain are synthesized through a single pathway, with different primary substrates determining which final siderophore molecule is synthesized (45). Strains BG33R (P. synxantha) and A506 (P. fluorescens) also have the gene clusters necessary for the biosynthesis and uptake of a pseudomine-like molecule similar to that found in ATCC 17400, but the functionality of this molecule has not yet been demonstrated (49, 119). The full complement of genes necessary for the biosynthesis and efflux of a hemophore, which allows for the chelation and transport of heme through a specific outer membrane (49), are also present in multiple P. fluorescens strains, but it is not known how and when hemophores are utilized by P. fluorescens. Much work remains on identifying the spectrum of siderophores produced by P. fluorescens strains, as well as determining their role in the physiology of these organisms under different conditions, including polymicrobial competition.
Like many other members within its genus, P. fluorescens produces a range of pigments, with and without siderophore ability. Due to the ability of P. fluorescens to grow at temperatures as low as 4°C, contamination of food products can be a problem (120). In 2010, European consumers noticed that some mozzarella products were blue instead of white, and extremely high levels of P. fluorescens, up to 106 CFU/g, were identified on the “blue” cheese samples (121). Beyond being blue, little is known about this particular pigment produced by P. fluorescens. Pyocyanin, another blue pigment, is produced by P. aeruginosa, but this secondary metabolite has not yet been identified in P. fluorescens (122). This incident indicated either the emergence of a new strain of P. fluorescens that had acquired the biosynthesis machinery for a new blue pigment or horizontal acquisition of the biosynthesis machinery from another, closely related Pseudomonas strain.

Two-Component Gene Systems

P. fluorescens also contains a two-component GacS-GacA system that plays a role in environmental sensing. This system controls the expression of multiple secondary metabolites and enzymes in P. fluorescens, including DAPG, pyoluteorin, HCN, phospholipase C, and exoprotease (123 126). In P. aeruginosa, GacA controls gene expression through acylated homoserine lactone (AHL) signaling (127, 128). However, GacA can also function independently of AHL signaling (127), and this AHL-independent GacA cascade has been reported for P. fluorescens strain CHA0 (129). The diffusible non-AHL bacterial signal, whose chemical nature is still under investigation, turns on and regulates a two-component GacS-GacA system that activates the transcription of a novel small, noncoding RNA, RsmY (129). RsmY then combines with a riboregulator (RsmA), which is a small, untranslated RNA that can regulate cellular processes (130 133), to positively regulate the expression of downstream genes at a posttranscriptional level (65).

Quorum Sensing and Biofilms

Bacteria are able to regulate their population density through the release and sensing of signal molecules, i.e., quorum sensing (134, 135). Quorum sensing involves regulation of genes that control motility (swimming and swarming), antibiotic synthesis, and biofilm formation. Genes involved in biofilm formation and quorum sensing are found in the core genome of the P. fluorescens species complex (49). Quorum sensing and biofilm formation are integral to the many environmental niches occupied by P. fluorescens and allow it to colonize surfaces such as hospital equipment and food-grade stainless steel surfaces (52, 136), as well as the surfaces of plants, showerheads, and even indoor wall surfaces (23, 24, 137). P. fluorescens readily forms biofilms with highly complex, three-dimensional (3-D) structures (Fig. 6 ) (20, 52 56), and strains that form plant-associated biofilms are often important biocontrol agents that protect plants against pathogenic fungi (54, 138). Less is known about P. fluorescens biofilm formation on mammalian surfaces, though the adaption to a 37°C permissive growth range is linked to biofilm formation on human cells (53). Thus, whether on plants or human cells, biofilm formation is likely important for successful long-term colonization by P. fluorescens.
FIG 6 Scanning electron micrographs of P. fluorescens biofilms. For these photomicrographs, Baum et al. prepared and cryopreserved 14-day biofilms from P. fluorescens EvS4-B1 monocultures (56). (A) Fibrillary structures made up of twisted fibers (arrow). Bar = 1 μm. (B) Flat sheets of material (arrowheads), with some of the sheets wrapped around other structures (arrow). Bar = 20 μm. (C) The inside core of the “wrapped” structures, consisting of bacteria (B) embedded in an extracellular matrix of particulate matter, and a thin sheet of material (arrow). Bar = 1 μm. (D) The outer sheet (arrowheads), which envelops an inner core consisting of fibers forming irregular network-like structures (arrows). Bar = 10 μm. (E) Network consisting of fibers arranged in a periodic pattern, with bacteria (arrows) dispersed throughout the network. Bar = 2 μm. (F) A sheet of material (S), consisting of extracellular material and dead cells, covering and attaching to the fiber network and including associated bacteria (B) and particulate matter (P). Bar = 2 μm. (Reprinted from BMC Microbiology [56] under a Creative Commons license [].)
Two types of quorum sensing systems have been described for P. fluorescens: the AHL/lux and hdtS systems. In Gram-negative bacteria, AHL molecules are produced by LuxI-like proteins and interact with LuxR-like proteins to form dual AHL-LuxR complexes. This AHL-LuxR complex then binds lux boxes of quorum sensing-regulated genes in order to either turn on/up or off/down their expression (139). A luxI-luxR-like system in P. fluorescens was first discovered in the strain NCIMB 10586 and was termed the mpuI-mpuR system due to its regulation of the antimicrobial mupirocin biosynthesis pathway (140). Another quorum sensing system, the hdtS system, was later discovered in P. fluorescens strain F113 (141). The hdtS gene encodes a novel AHL synthase that produces separate signaling molecules: an N-(3-hydroxy-7-cis-tetradecenoyl)homoserine lactone (3-OH-C14:1-AHL), an N-decanoylhomoserine lactone (C10-AHL), and a C6-AHL. Though the signaling molecules and synthase have been elucidated, the genes regulated by the hdtS system are still unknown, and no detectable phenotype in F113 has yet been linked to the signaling molecules (141).
The second messenger cyclic di-GMP (c-di-GMP) is essential for regulation of steps involved in biofilm formation, including the production of LapA, an adhesive protein necessary for P. fluorescens attachment to surfaces (142). LapA is negatively regulated by the periplasmic protease LapG and positively regulated by the inner membrane protein LapD (143). LapG typically cleaves LapA from the bacterial surface, but when LapD is bound by c-di-GMP, LapD undergoes a conformation change that allows it to bind to LapG, inhibiting LapA cleavage. Diguanylate cyclases catalyze c-di-GMP synthase activity, and in P. fluorescens Pf0-1, there are a total of 43 potential diguanylate cyclases encoded in the genome, each potentially connected to a different aspect of biofilm formation (144).

Type III Secretion Systems

Type III secretion systems (T3SSs) are molecular needle-like complexes that act like syringes to deliver bacterial proteins, called effectors, from the bacterial cytoplasm directly into host cells (92) (Fig. 7). T3SSs are highly conserved genomic clusters typically found in bacteria that have close interactions with eukaryotic hosts (often transferred horizontally between phylogenetically unrelated bacteria), and the type of T3SS usually mirrors the type of interaction a bacterium has with the eukaryotes in its environment. The first T3SS was described for Yersinia, which delivers Yop (Yersinia outer protein) effector proteins into human host cells (145, 146). A total of five different T3SS groups have since been described: the Ysc group (which includes the Yersinia Ysc, P. aeruginosa Psc, Bordetella Bsc, Rhizobium Rsc, and Chlamydia sp. T3SSs), the Hrp1 group (found in non-aeruginosa Pseudomonas spp. and Erwinia spp.), the Hrp2 group (found in Xanthomonas spp. and Ralstonia spp.), the Inv/Mxi/Spa group (which includes the Salmonella SPI-I, Shigella sp., and Yersinia enterocolitica Ysa T3SSs and T3SS2 of enterohemorrhagic E. coli [EHEC]), and the Esa/Ssa group (including the Salmonella SPI-2 and enteropathogenic E. coli [EPEC] T3SSs and EHEC T3SS1) (147).
FIG 7 Type III secretion systems in P. fluorescens. The components and structures of the SPI-I and Hrp1 systems are shown, with lists of the corresponding strains in which these systems have been identified.
The Hrp1 family is the most common T3SS found among P. fluorescens strains (46 50). The Hrp (hypersensitivity response and pathogenicity) system triggers the hypersensitivity defense response in resistant plants, while leading to disease in susceptible plants, and was first described for P. syringae (148). Like the T3SS found in Yersinia, the Hrp1 system is involved in delivering bacterial proteins directly into host cells (149 152) (Fig. 7). While the fully sequenced P. fluorescens strains SBW25, BG33R, A506, SS101, Q8r1-96, and Q2-87 have at least one copy of the Hrp1 family T3SS, Pf0-1 and Pf-5 do not carry the gene cluster at all (49, 153). The activity and functionality of the Hrp1 system have been worked out for only a couple of the strains in which it has been found. The Hrp1 T3SS of P. fluorescens Pf29Arp, a strain known for its ability to reduce the severity of wheat take-all, shows activity during the colonization of wheat rhizospheres (46). The homologous Hrp1 T3SS in strain SBW25 is induced during sugar beet rhizosphere colonization (154) and can induce a hypersensitive response in tobacco (47, 155). Interestingly, in addition to Hrp1 system effectors, SBW25 also contains the T3SS effector ExoY (156), which in P. aeruginosa targets the actin cytoskeleton of eukaryotic cells (157). Since most of the work on the functionality of the Hrp1 T3SS in P. fluorescens has been done in vitro, many of the target host cells are still unknown, but the presence of the ExoY effector protein in some strains suggests that there might be an additional, nonplant use of this T3SS in SBW25 and genetically related strains.
Additional evidence that P. fluorescens strains may target their T3SSs against eukaryotic cells was provided in 2013, when a SPI-I-like T3SS gene cluster was discovered in strain F113 (51) (Fig. 7). The F113 strain was originally isolated from sugar beet rhizospheres in Ireland (158) and can inhibit the growth of plant-pathogenic bacteria, oomycetes, fungi, and a wide range of nematodes (159 161). Predation against protozoa in both terrestrial and aquatic environments is an important factor influencing bacterial community makeup and behavior (37, 38, 162). In F113, the SPI-I T3SS hilA promoter shows increased expression during close contact with the amoeba Acanthamoeba castellanii, suggesting that this T3SS is directly involved in protecting the bacterium from amoeba predation. Interestingly, both the Hrp1 and SPI-I systems in F113 appear to be involved in protection against predation by the worm Caenorhabditis elegans (51). A similar result was found with the Hrp1 system of P. fluorescens CHA0 (163). Additional SPI-I T3SSs have also been found in P. fluorescens strains HK44 (164) and Q2-87 (49), providing further evidence of T3SS action outside the plant ecosphere. Thus, the identification of multiple T3SSs across the P. fluorescens species complex that target plant and nonplant eukaryotic cells supports the model of a wider interaction of P. fluorescens with eukaryotic hosts.


Environmental isolates of P. fluorescens have an optimal temperature growth range of 25 to 30°C and are not virulent to human cells, but certain strains of P. fluorescens isolated from clinical samples have a higher permissive growth range, up to 37°C, and show increased virulence against human cells (53, 57 59). Two P. fluorescens strains, MFY162 and MFN1032, can adhere to human glial cells in culture, and MFN1032 can induce apoptosis. Originally isolated from an individual with a lung infection (57), MFN1032 not only exhibits cytotoxicity on human intestinal epithelial cells in vitro but also triggers a proinflammatory response (165). Human airway epithelial cells exposed to a different strain of P. fluorescens have been shown to trigger both antiapoptotic responses, via the epidermal growth factor receptor (EGFR), and interleukin-8 (IL-8) production, via Toll-like receptor 4 (TLR4)-independent NF-κB signaling pathways (166). Exposure to a strain of P. fluorescens isolated from a moldy building decreased viability of mouse macrophages (RAW cells) while inducing production of nitric oxide, tumor necrosis factor (TNF), and IL-6 (167).
On red blood cells, P. fluorescens MFN1032 displays both cell-associated and secretion-dependent hemolytic activity. The secretion-dependent pathway is positively regulated by the GacS-GacA two-component system (58), the same two-component system that regulates phase variation in this strain (168). This hemolytic activity involves the production of phospholipase C and biosurfactants, similar to that seen for pathogenic P. aeruginosa (169). Similarities between P. aeruginosa and P. fluorescens also exist within the functionality of the cell-associated hemolytic activity of MFN1032. The cell-associated hemolytic activity is independent of the secretion-association hemolytic activity, is active at 37°C, occurs without the secretion of phospholipase C and biosurfactants, and does not depend on the GacS-GacA two-component system (170). In P. aeruginosa, cell-associated hemolytic activity occurs alongside type III secretion of the PcrV, PopB, and PopD effectors (171). MFN1032 also harbors the genes necessary to produce a T3SS (170), the hrcRST gene cluster, which shares a high level of homology to the hrcRST genes of the hrpU operon in P. syringae DC3000. When this operon is mutated, MFN1032 is no longer able to produce cell-associated hemolytic activity (170). In P. aeruginosa, similar mutations in the T3SS also abolish its cell-associated hemolytic activity. Thus, adaptation of P. fluorescens MFN1032 results in an increased temperature permissivity along with hemolytic activity against human cells that is similar to that found in P. aeruginosa.
The production of cyclolipopeptides (CLPs) by P. fluorescens MFN1032 is another functional characteristic that is altered during a shift to higher temperatures. Cyclolipopeptides are the most widely studied biosurfactants produced by P. fluorescens and are involved in swarming motility, biofilm formation, and colonization of host surfaces (172). If MFN1032 is grown for multiple generations at 37°C, CLP functionality is lost, with ∼4 × 10−3 CLP-deficient mutants found per generation (58). High mutation rates, inversions of DNA segments, DNA methylation, and epigenetic switches are all mechanisms that bacteria use to alter their genomes in the process of adaptation, which allows survival in changing environments and an increase in overall fitness with time (173). In the case of the P. aeruginosa T3SS, there is an epigenetic switch between a noninducible and an inducible state (168). Using a Boolean modeling system, a similar epigenetic switch has been shown to be the likely mechanism by which P. fluorescens regulates its CLP production (168). In much the same way that chronic P. aeruginosa strains lose the ability to produce biofilms after long-term growth in a cystic fibrosis lung (174), P. fluorescens also has a mechanism to turn off energy-expensive surfactant production after long-term growth at physiologically relevant temperatures.


P. fluorescens as a Disease-Causing Agent

The bloodstream is by far the most common site reported for P. fluorescens infection (opportunistic) in humans. Most reported cases have been iatrogenic, with bacteremia attributable to either transfusion of contaminated blood products (7 12) or use of contaminated equipment associated with intravenous infusions (13 17). P. fluorescens bacteremia has occurred in outbreaks (8, 13 16), with the largest affecting at least 80 patients in 6 states after indirect exposure to contaminated heparinized saline flushes prepared at a common compounding pharmacy (16). Of these patients, 41% were bacteremic more than 84 days after exposure; all of these delayed-onset patients had indwelling ports for venous access, indicating that P. fluorescens can persist endovascularly when an indwelling catheter is in place. The abilities to grow at refrigerated temperatures and to form biofilms on fomite surfaces make P. fluorescens contamination a particular problem for blood infusion-related infections and outbreaks.
Confounding the diagnosis of P. fluorescens bacteremia is the well-described phenomenon of “pseudobacteremia” due to environmental contamination of blood culture collection bottles and equipment by the organism (175 182). Indeed, in a systematic review of the medical literature, more positive P. fluorescens blood culture results were attributable to pseudobacteremia (175 182) than to true bacteremia (8 17, 183 189). Sources have included blood culture bottles cleaned with contaminated disinfectant (179) and, most commonly, contaminated blood collection tubes used prior to culture bottle inoculation (176, 178, 180 182). Despite not reflecting “true” human pathology, pseudobacteremia is a legitimate clinical problem, resulting in diagnostic confusion for clinicians and inappropriate antibiotic exposure for patients (181). The diagnosis of pseudobacteremia should be considered when patient symptoms are discordant with disseminated bacterial infection and bacteria that are uncommon infectious agents (such as P. fluorescens) are isolated, especially in a geographic or temporal cluster.
Identification of P. fluorescens as an acute cause of infection (opportunistic or primary) in sites other than the blood has been rare and sporadic (Table 1). Two reports have identified P. fluorescens in skin wounds and abscesses following dog bites (190, 191), and in one instance, the patient subsequently developed disseminated P. fluorescens bacteremia (191). P. fluorescens has been implicated as a cause of acute bacterial cystitis (192 194), both with (192) and without (193) the presence of an indwelling urinary catheter. In a study comparing the oral microbiomes of 20 solid organ transplant recipients and 19 nonimmunosuppressed control subjects, P. fluorescens was abundant in the saliva of nearly 50% of transplant subjects while being nearly absent from nontransplant controls (1). In another study of 258 stomach wall biopsy specimens acquired from patients with various upper gastrointestinal disorders, 93% had evidence of the presence of P. fluorescens (identified via both culture-dependent and -independent methods) (2). Thus, P. fluorescens can clearly establish itself in diseased humans, but questions remain about the pathogenicity of such interactions and whether the involved strains are all restricted to a specific clade.

P. fluorescens in Respiratory Diseases

While P. fluorescens has repeatedly been cultured from respiratory specimens, its role in pneumonia or other respiratory infections is unclear. P. fluorescens has been cultured from the tracheal aspirates of patients receiving mechanical ventilation and subsequently identified as an organism in the humidifier water used in the ventilator circuit (195), but it is unclear if the tracheal aspirate culture results reflected acute infection or benign colonization. In another case study, during recovery from a recent polymicrobial peritonitis, a patient developed clinical evidence of pneumonia, with sputum cultures that were positive for P. fluorescens (196). The patient improved after treatment with a third-generation cephalosporin, and subsequent sputum cultures did not grow P. fluorescens. In another report, P. fluorescens is mentioned in the etiology of community-acquired pneumonia in a single patient, but clinical details are lacking (197). Using amplification of bacterial 16S rRNA genes, another study detected P. fluorescens and other bacteria in the bronchoalveolar lavage fluid acquired from a single patient with clinically diagnosed ventilator-associated pneumonia (198). Most notably, in a survey of over 1,000 respiratory cultures acquired from subjects with cystic fibrosis, Klinger and Thomassen identified the organism in roughly 2% of specimens (199) and considered the organism a colonizer rather than an acute pathogen. We have reported, using bronchoalveolar lavage fluid acquired from lung transplant recipients, that P. fluorescens is frequently identified in this patient population, in the absence of evidence of acute infection (3).
In a survey of bacterial culture isolates at the University of Michigan Hospital, P. fluorescens was cultured from respiratory specimens with relative frequency (3) (Table 2). Over an 11-year period, P. fluorescens was cultured from over 240 distinct respiratory specimens, or roughly 2 specimens per month. Among patients with positive P. fluorescens respiratory cultures, the most common underlying pulmonary condition was cystic fibrosis (38.8% of all isolates), followed by other chronic airway diseases (chronic obstructive pulmonary disease [COPD], asthma, and non-cystic-fibrosis bronchiectasis [16.1%]). P. fluorescens was often coisolated with other organisms, most often (85.1%) species designated “oral flora” by the clinical microbiology laboratory, followed by P. aeruginosa (25.6%), Staphylococcus aureus (15.7%), and Stenotrophomonas maltophilia (11.6%). In no cases was P. fluorescens the unambiguous causative agent in a monomicrobial pneumonia. This survey highlights the fact that P. fluorescens is commonly isolated from human clinical samples in cases where it is not the cause of active acute infection. This contrasts with much of the literature, which states that P. fluorescens is found only in human hosts in extreme cases of outbreak or contamination. In addition, no reports were created in response to these P. fluorescens cultures, revealing that the number of reports in the literature also likely do not reflect the consistency with which P. fluorescens is cultured from clinical samples.

P. fluorescens and Inflammatory Bowel Disease

P. fluorescens has also been speculated to have a possible role in the pathogenesis of Crohn's disease and other inflammatory conditions. I2, a peptide encoded by P. fluorescens, was found to be detected more frequently in gut wall biopsy specimens of patients with Crohn's disease than in those of patients with other bowel diseases, and a similar difference was noted in detection of circulating anti-I2 antibodies (200). Interestingly, there was no evidence of P. fluorescens in the stool of subjects with Crohn's disease, by either culture or microbe-specific PCR. The same I2 sequence was also found in the proximal colon, cecum, and distal small intestine in C57BL/6J mice, suggesting that P. fluorescens can exist in the intestinal microbiota of multiple mammalian species (201). In TLR4- and MyD88-knockout mice that were treated with dextran sodium sulfate, the resulting colitis and impaired immune response led to systemically detectable P. fluorescens, such that it could be cultured from the mesenteric lymph nodes (202). Approximately 50% of Crohn's disease patients develop serum anti-I2 antibodies, and in some studies, this seroreactivity has correlated with the success of therapies aimed at the microbiome rather than the immune system (18 22). I2 is encoded within the P. fluorescens pfiT gene and has T-cell superantigen activity (203). The presence of anti-I2 serum antibodies in Crohn's disease patients was subsequently shown to be positively associated with the prognosis (19). Anti-I2 antibodies have also been associated with the diagnosis of celiac disease, including a decrease in titer after a gluten-free diet is initiated (204, 205), of ankylosing spondylitis (206), and of chronic granulomatous disease (207). Whether P. fluorescens directly contributes to these chronic inflammatory conditions or whether anti-I2 antibodies are only indirect biomarkers of disease is undetermined.


Despite being identified in the last half of the 1800s and more recent associations with human disease, the role of the P. fluorescens species complex in human health and disease remains largely unexplored. Research in the last 2 decades on the genetic, molecular, environmental, and immunological aspects of the P. fluorescens species complex has begun to expand our understanding of these bacteria overall and to lay the groundwork for investigating their role in human health. Full-genome sequencing and comparison led to the discovery of potential pathogenic traits (such as T3SSs and T-cell superantigens) and further revealed the high level of genetic diversity within the P. fluorescens species complex. The discovery of human-adapted P. fluorescens strains with higher permissive temperature ranges revealed that these bacteria can readily exist outside plant and soil niches, and even potentially change their functional phenotypes in response to a new, mammal-based niche. Clinical surveys have also found that P. fluorescens is regularly cultured from clinical samples even in the absence of acute infection or outbreak. Studies are beginning to identify P. fluorescens via high-throughput sequencing in multiple sites of the human body, suggesting that the human-P. fluorescens connection will only grow as more studies are reported.
However, there is still much more that is unknown about the role of the P. fluorescens species complex in human disease. Taxonomic classifications within the P. fluorescens species complex are still in flux; a general consensus on what constitutes a P. fluorescens strain would codify classification and greatly assist in functional microbiology research, as well as the clinical microbiology lab and clinician. Almost nothing is known about the host response to P. fluorescens, and while correlations have been found between P. fluorescens-specific antibodies and Crohn's disease, the mechanisms underlying this connection have not been identified. Finally, there is a glaring disparity between reports in the medical literature that only find P. fluorescens infections during outbreaks/extreme situations and clinical surveys that readily identify P. fluorescens in human samples in the absence of acute disease. The former suggest that P. fluorescens is accidentally associated with human hosts through contamination or when the host is immunocompromised; the latter suggest that there are strains of P. fluorescens that can colonize and thrive in a human host. Additional work on the genomics, molecular microbiology, and host immune response to the P. fluorescens species complex will provide insight into the roles these bacteria play in human health and disease.


The following funding sources have provided research support for the authors: The National Institute of Allergy and Infectious Diseases (B.S.S. [grant T32AI007528]), The National Heart, Lung and Blood Institute (G.B.H. [grants U01HL098961 and R01HL114447] and R.P.D. [grant T32HL00774921]), The Cystic Fibrosis Foundation (J.J.L.), and The Nesbitt Program for Cystic Fibrosis Research (J.J.L. and G.B.H.).
We thank the following individuals for their contributions to the manuscript: Karin J. Ekholm for translation of the Baader 1887 reference, Ellen Hunter for her assistance with the photographs of the Gram stains, and Patrick Lane for his assistance with the graphics.


Diaz PI, Hong BY, Frias-Lopez J, Dupuy AK, Angeloni M, Abusleme L, Terzi E, Ioannidou E, Strausbaugh LD, and Dongari-Bagtzoglou A. 2013. Transplantation-associated long-term immunosuppression promotes oral colonization by potentially opportunistic pathogens without impacting other members of the salivary bacteriome. Clin. Vaccine Immunol. 20:920–930.
Patel SK, Pratap CB, Verma AK, Jain AK, Dixit VK, and Nath G. 2013. Pseudomonas fluorescens-like bacteria from the stomach: a microbiological and molecular study. World J. Gastroenterol. 19:1056–1067.
Dickson RP, Erb-Downward JR, Freeman CM, Walker N, Scales BS, Beck JM, Martinez FJ, Curtis JL, Lama VN, and Huffnagle GB. 2014. Changes in the lung microbiome following lung transplantation include the emergence of two distinct Pseudomonas species with distinct clinical associations. PLoS One 9:e97214.
Stenhouse MA and Milner LV. 1992. A survey of cold-growing gram-negative organisms isolated from the skin of prospective blood donors. Transfus. Med. 2:235–237.
Wagner J, Short K, Catto-Smith AG, Cameron DJ, Bishop RF, and Kirkwood CD. 2008. Identification and characterisation of Pseudomonas 16S ribosomal DNA from ileal biopsies of children with Crohn's disease. PLoS One 3:e3578.
Baader A and Garre C. 1887. Über Antagonisten unter den Bacterien. Corresp. Bl. Schweiz. Ärzte 13:385–392.
Gibaud M, Martin-Dupont P, Dominguez M, Laurentjoye P, Chassaing B, and Leng B. 1984. Pseudomonas fluorescens septicemia following transfusion of contaminated blood. Presse Med. 13:2583–2584.
Hsueh PR, Teng LJ, Pan HJ, Chen YC, Sun CC, Ho SW, and Luh KT. 1998. Outbreak of Pseudomonas fluorescens bacteremia among oncology patients. J. Clin. Microbiol. 36:2914–2917.
Khabbaz RF, Arnow PM, Highsmith AK, Herwaldt LA, Chou T, Jarvis WR, Lerche NW, and Allen JR. 1984. Pseudomonas fluorescens bacteremia from blood transfusion. Am. J. Med. 76:62–68.
Murray AE, Bartzokas CA, Shepherd AJ, and Roberts FM. 1987. Blood transfusion-associated Pseudomonas fluorescens septicaemia: is this an increasing problem? J. Hosp. Infect. 9:243–248.
Pittman M. 1953. A study of bacteria implicated in transfusion reactions and of bacteria isolated from blood products. J. Lab. Clin. Med. 42:273.
Scott J, Boulton FE, Govan JR, Miles RS, McClelland DB, and Prowse CV. 1988. A fatal transfusion reaction associated with blood contaminated with Pseudomonas fluorescens. Vox Sang. 54:201–204.
Benito N, Mirelis B, Luz Galvez M, Vila M, Lopez-Contreras J, Cotura A, Pomar V, March F, Navarro F, Coll P, and Gurgui M. 2012. Outbreak of Pseudomonas fluorescens bloodstream infection in a coronary care unit. J. Hosp. Infect. 82:286–289.
Centers for Disease Control and Prevention. 2005. Pseudomonas bloodstream infections associated with a heparin/saline flush—Missouri, New York, Texas, and Michigan, 2004–2005. MMWR Morb. Mortal. Wkly. Rep. 54:269–272.
Centers for Disease Control and Prevention. 2006. Update: delayed onset Pseudomonas fluorescens bloodstream infections after exposure to contaminated heparin flush—Michigan and South Dakota, 2005–2006. MMWR Morb. Mortal. Wkly. Rep. 55:961–963.
Gershman MD, Kennedy DJ, Noble-Wang J, Kim C, Gullion J, Kacica M, Jensen B, Pascoe N, Saiman L, McHale J, Wilkins M, Schoonmaker-Bopp D, Clayton J, Arduino M, and Srinivasan A. 2008. Multistate outbreak of Pseudomonas fluorescens bloodstream infection after exposure to contaminated heparinized saline flush prepared by a compounding pharmacy. Clin. Infect. Dis. 47:1372–1379.
Sarubbi FA Jr, Wilson B, Lee M, and Brokopp C. 1978. Nosocomial meningitis and bacteremia due to contaminated amphotericin B. JAMA 239:416–418.
Landers CJ, Cohavy O, Misra R, Yang H, Lin YC, Braun J, and Targan SR. 2002. Selected loss of tolerance evidenced by Crohn's disease-associated immune responses to auto- and microbial antigens. Gastroenterology 123:689–699.
Arnott ID, Landers CJ, Nimmo EJ, Drummond HE, Smith BK, Targan SR, and Satsangi J. 2004. Sero-reactivity to microbial components in Crohn's disease is associated with disease severity and progression, but not NOD2/CARD15 genotype. Am. J. Gastroenterol. 99:2376–2384.
Iltanen S, Tervo L, Halttunen T, Wei B, Braun J, Rantala I, Honkanen T, Kronenberg M, Cheroutre H, Turovskaya O, Autio V, and Ashorn M. 2006. Elevated serum anti-I2 and anti-OmpW antibody levels in children with IBD. Inflamm. Bowel Dis. 12:389–394.
Mow WS, Landers CJ, Steinhart AH, Feagan BG, Croitoru K, Seidman E, Greenberg GR, and Targan SR. 2004. High-level serum antibodies to bacterial antigens are associated with antibiotic-induced clinical remission in Crohn's disease: a pilot study. Dig. Dis. Sci. 49:1280–1286.
Spivak J, Landers CJ, Vasiliauskas EA, Abreu MT, Dubinsky MC, Papadakis KA, Ippoliti A, Targan SR, and Fleshner PR. 2006. Antibodies to I2 predict clinical response to fecal diversion in Crohn's disease. Inflamm. Bowel Dis. 12:1122–1130.
Silby MW, Cerdeno-Tarraga AM, Vernikos GS, Giddens SR, Jackson RW, Preston GM, Zhang XX, Moon CD, Gehrig SM, Godfrey SA, Knight CG, Malone JG, Robinson Z, Spiers AJ, Harris S, Challis GL, Yaxley AM, Harris D, Seeger K, Murphy L, Rutter S, Squares R, Quail MA, Saunders E, Mavromatis K, Brettin TS, Bentley SD, Hothersall J, Stephens E, Thomas CM, Parkhill J, Levy SB, Rainey PB, and Thomson NR. 2009. Genomic and genetic analyses of diversity and plant interactions of Pseudomonas fluorescens. Genome Biol. 10:R51.
Feazel LM, Baumgartner LK, Peterson KL, Frank DN, Harris JK, and Pace NR. 2009. Opportunistic pathogens enriched in showerhead biofilms. Proc. Natl. Acad. Sci. U. S. A. 106:16393–16399.
Haas D and Defago G. 2005. Biological control of soil-borne pathogens by fluorescent pseudomonads. Nat. Rev. Microbiol. 3:307–319.
Laursen JB and Nielsen J. 2004. Phenazine natural products: biosynthesis, synthetic analogues, and biological activity. Chem. Rev. 104:1663–1686.
Weller DM, Landa BB, Mavrodi OV, Schroeder KL, De La Fuente L, Blouin Bankhead S, Allende Molar R, Bonsall RF, Mavrodi DV, and Thomashow LS. 2007. Role of 2,4-diacetylphloroglucinol-producing fluorescent Pseudomonas spp. in the defense of plant roots. Plant Biol. (Stuttg.) 9:4–20.
Mavrodi DV, Blankenfeldt W, and Thomashow LS. 2006. Phenazine compounds in fluorescent Pseudomonas spp. biosynthesis and regulation. Annu. Rev. Phytopathol. 44:417–445.
Ramette A, Moenne-Loccoz Y, and Defago G. 2003. Prevalence of fluorescent pseudomonads producing antifungal phloroglucinols and/or hydrogen cyanide in soils naturally suppressive or conducive to tobacco black root rot. FEMS Microbiol. Ecol. 44:35–43.
Keel C, Weller DM, Natsch A, Defago G, Cook RJ, and Thomashow LS. 1996. Conservation of the 2,4-diacetylphloroglucinol biosynthesis locus among fluorescent Pseudomonas strains from diverse geographic locations. Appl. Environ. Microbiol. 62:552–563.
Moynihan JA, Morrissey JP, Coppoolse ER, Stiekema WJ, O'Gara F, and Boyd EF. 2009. Evolutionary history of the phl gene cluster in the plant-associated bacterium Pseudomonas fluorescens. Appl. Environ. Microbiol. 75:2122–2131.
Takahashi M, Matsumoto S, Iwasaki S, and Yahara I. 1990. Molecular basis for determining the sensitivity of eucaryotes to the antimitotic drug rhizoxin. Mol. Gen. Genet. 222:169–175.
Gross H and Loper JE. 2009. Genomics of secondary metabolite production by Pseudomonas spp. Nat. Prod. Rep. 26:1408–1446.
Tsuruo T, Oh-hara, Iida TH, Tsukagoshi S, Sato Z, Matsuda I, Iwasaki S, Okuda S, Shimizu F, Sasagawa K, Fukami M, Fukuda K, and Arakawa M. 1986. Rhizoxin, a macrocyclic lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine-resistant sublines. Cancer Res. 46:381–385.
Schnider U, Keel C, Blumer C, Troxler J, Defago G, and Haas D. 1995. Amplification of the housekeeping sigma factor in Pseudomonas fluorescens CHA0 enhances antibiotic production and improves biocontrol abilities. J. Bacteriol. 177:5387–5392.
Sarniguet A, Kraus J, Henkels MD, Muehlchen AM, and Loper JE. 1995. The sigma factor sigma s affects antibiotic production and biological control activity of Pseudomonas fluorescens Pf-5. Proc. Natl. Acad. Sci. U. S. A. 92:12255–12259.
Rosenberg K, Bertaux J, Krome K, Hartmann A, Scheu S, and Bonkowski M. 2009. Soil amoebae rapidly change bacterial community composition in the rhizosphere of Arabidopsis thaliana. ISME J. 3:675–684.
Ronn R, McCaig AE, Griffiths BS, and Prosser JI. 2002. Impact of protozoan grazing on bacterial community structure in soil microcosms. Appl. Environ. Microbiol. 68:6094–6105.
Umio S, Kawanishi T, Kamishita T, and Mine Y. January 1987. Antifungal composition employing pyrrolnitrin in combination with an imidazole compound. US patent 4636520.
Fuller AT, Mellows G, Woolford M, Banks GT, Barrow KD, and Chain EB. 1971. Pseudomonic acid: an antibiotic produced by Pseudomonas fluorescens. Nature 234:416–417.
Bork K, Brauers J, and Kresken M. 1989. Efficacy and safety of 2% mupirocin ointment in the treatment of primary and secondary skin infections—an open multicentre trial. Br. J. Clin. Pract. 43:284–288.
Strock LL, Lee MM, Rutan RL, Desai MH, Robson MC, Herndon DN, and Heggers JP. 1990. Topical Bactroban (mupirocin): efficacy in treating burn wounds infected with methicillin-resistant staphylococci. J. Burn Care Rehabil. 11:454–459.
Neilands JB. 1981. Iron absorption and transport in microorganisms. Annu. Rev. Nutr. 1:27–46.
Youard ZA, Mislin GL, Majcherczyk PA, Schalk IJ, and Reimmann C. 2007. Pseudomonas fluorescens CHA0 produces enantio-pyochelin, the optical antipode of the Pseudomonas aeruginosa siderophore pyochelin. J. Biol. Chem. 282:35546–35553.
Wuest WM, Sattely ES, and Walsh CT. 2009. Three siderophores from one bacterial enzymatic assembly line. J. Am. Chem. Soc. 131:5056–5057.
Marchi M, Boutin M, Gazengel K, Rispe C, Gauthier JP, Guillerm-Erckelboudt AY, Lebreton L, Barret M, Daval S, and Sarniguet A. 2013. Genomic analysis of the biocontrol strain Pseudomonas fluorescens Pf29Arp with evidence of T3SS and T6SS gene expression on plant roots. Environ. Microbiol. Rep. 5:393–403.
Preston GM, Bertrand N, and Rainey PB. 2001. Type III secretion in plant growth-promoting Pseudomonas fluorescens SBW25. Mol. Microbiol. 41:999–1014.
Rezzonico F, Binder C, Defago G, and Moenne-Loccoz Y. 2005. The type III secretion system of biocontrol Pseudomonas fluorescens KD targets the phytopathogenic Chromista Pythium ultimum and promotes cucumber protection. Mol. Plant Microbe Interact. 18:991–1001.
Loper JE, Hassan KA, Mavrodi DV, Davis EW 2nd, Lim CK, Shaffer BT, Elbourne LD, Stockwell VO, Hartney SL, Breakwell K, Henkels MD, Tetu SG, Rangel LI, Kidarsa TA, Wilson NL, van de Mortel JE, Song C, Blumhagen R, Radune D, Hostetler JB, Brinkac LM, Durkin AS, Kluepfel DA, Wechter WP, Anderson AJ, Kim YC, Pierson LS 3rd, Pierson EA, Lindow SE, Kobayashi DY, Raaijmakers JM, Weller DM, Thomashow LS, Allen AE, and Paulsen IT. 2012. Comparative genomics of plant-associated Pseudomonas spp.: insights into diversity and inheritance of traits involved in multitrophic interactions. PLoS Genet. 8:e1002784.
Redondo-Nieto M, Barret M, Morrisey JP, Germaine K, Martinez-Granero F, Barahona E, Navazo A, Sanchez-Contreras M, Moynihan JA, Giddens SR, Coppoolse ER, Muriel C, Stiekema WJ, Rainey PB, Dowling D, O'Gara F, Martin M, and Rivilla R. 2012. Genome sequence of the biocontrol strain Pseudomonas fluorescens F113. J. Bacteriol. 194:1273–1274.
Barret M, Egan F, Moynihan J, Morrissey JP, Lesouhaitier O, and O'Gara F. 2013. Characterization of the SPI-1 and Rsp type three secretion systems in Pseudomonas fluorescens F113. Environ. Microbiol. Rep. 5:377–386.
Tuttlebee CM, O'Donnell MJ, Keane CT, Russell RJ, Sullivan DJ, Falkiner F, and Coleman DC. 2002. Effective control of dental chair unit waterline biofilm and marked reduction of bacterial contamination of output water using two peroxide-based disinfectants. J. Hosp. Infect. 52:192–205.
Donnarumma G, Buommino E, Fusco A, Paoletti I, Auricchio L, and Tufano MA. 2010. Effect of temperature on the shift of Pseudomonas fluorescens from an environmental microorganism to a potential human pathogen. Int. J. Immunopathol. Pharmacol. 23:227–234.
Bianciotto V, Andreotti S, Balestrini R, Bonfante P, and Perotto S. 2001. Mucoid mutants of the biocontrol strain Pseudomonas fluorescens CHA0 show increased ability in biofilm formation on mycorrhizal and nonmycorrhizal carrot roots. Mol. Plant Microbe Interact. 14:255–260.
O'Toole GA and Kolter R. 1998. Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple, convergent signalling pathways: a genetic analysis. Mol. Microbiol. 28:449–461.
Baum MM, Kainovic A, O'Keeffe T, Pandita R, McDonald K, Wu S, and Webster P. 2009. Characterization of structures in biofilms formed by a Pseudomonas fluorescens isolated from soil. BMC Microbiol. 9:103.
Chapalain A, Rossignol G, Lesouhaitier O, Merieau A, Gruffaz C, Guerillon J, Meyer JM, Orange N, and Feuilloley MG. 2008. Comparative study of 7 fluorescent pseudomonad clinical isolates. Can. J. Microbiol. 54:19–27.
Rossignol G, Sperandio D, Guerillon J, Duclairoir Poc C, Soum-Soutera E, Orange N, Feuilloley MG, and Merieau A. 2009. Phenotypic variation in the Pseudomonas fluorescens clinical strain MFN1032. Res. Microbiol. 160:337–344.
Sperandio D, Decoin V, Latour X, Mijouin L, Hillion M, Feuilloley MG, Orange N, and Merieau A. 2012. Virulence of the Pseudomonas fluorescens clinical strain MFN1032 towards Dictyostelium discoideum and macrophages in relation with type III secretion system. BMC Microbiol. 12:223.
Almeida LA and Araujo R. 2013. Highlights on molecular identification of closely related species. Infect. Genet. Evol. 13:67–75.
Konstantinidis KT, Ramette A, and Tiedje JM. 2006. Toward a more robust assessment of intraspecies diversity, using fewer genetic markers. Appl. Environ. Microbiol. 72:7286–7293.
Moore ERB, Tindall BJ, Dos Santos VAPM, Pieper DH, Ramos JL, and Palleron NJ. 2006. Nonmedical: Pseudomonas, p 646–703. In Dworkin M, Falkow S, Rosenberg E, Schleifer K-H, and Stackebrandt E (ed), Prokaryotes: a handbook on the biology of bacteria, vol 6, 3rd ed. Springer, New York, NY.
Howell C and Stipanovic R. 1980. Suppression of Pythium ultimum-induced damping-off of cotton seedlings by Pseudomonas fluorescens and its antibiotic, pyoluteorin. Phytopathology 70:712–715.
De Souza JT, De Boer M, De Waard P, Van Beek TA, and Raaijmakers JM. 2003. Biochemical, genetic, and zoosporicidal properties of cyclic lipopeptide surfactants produced by Pseudomonas fluorescens. Appl. Environ. Microbiol. 69:7161–7172.
Valverde C, Heeb S, Keel C, and Haas D. 2003. RsmY, a small regulatory RNA, is required in concert with RsmZ for GacA-dependent expression of biocontrol traits in Pseudomonas fluorescens CHA0. Mol. Microbiol. 50:1361–1379.
Cosson P and Soldati T. 2008. Eat, kill or die: when amoeba meets bacteria. Curr. Opin. Microbiol. 11:271–276.
King EO, Ward MK, and Raney DE. 1954. Two simple media for the demonstration of pyocyanin and fluorescin. J. Lab. Clin. Med. 44:301–307.
Lowbury EJ and Collins AG. 1955. The use of a new cetrimide product in a selective medium for Pseudomonas pyocyanea. J. Clin. Pathol. 8:47–48.
Bunker ST, Bates TC, and Oliver JD. 2004. Effects of temperature on detection of plasmid or chromosomally encoded gfp- and lux-labeled Pseudomonas fluorescens in soil. Environ. Biosafety Res. 3:83–90.
Oliver J. 1993. Formation of viable but nonculturable cells, p 239–272. In Kjelleberg S (ed), Starvation in bacteria. Plenum Press, New York, NY.
Rowan N. 2004. Viable but non-culturable forms of food and waterborne bacteria: quo vadis? Trends Food Sci. Technol. 15:462–467.
Oliver JD. 1995. The viable but non-culturable state in the human pathogen Vibrio vulnificus. FEMS Microbiol. Lett. 133:203–208.
Oliver JD. 2005. The viable but nonculturable state in bacteria. J. Microbiol. 43(Spec Issue):93–100.
Mulet M, Lalucat J, and Garcia-Valdes E. 2010. DNA sequence-based analysis of the Pseudomonas species. Environ. Microbiol. 12:1513–1530.
Peix A, Ramirez-Bahena MH, and Velazquez E. 2009. Historical evolution and current status of the taxonomy of genus Pseudomonas. Infect. Genet. Evol. 9:1132–1147.
Anzai Y, Kim H, Park JY, Wakabayashi H, and Oyaizu H. 2000. Phylogenetic affiliation of the pseudomonads based on 16S rRNA sequence. Int. J. Syst. Evol. Microbiol. 50:1563–1589.
Palleroni NJ. 2010. The Pseudomonas story. Environ. Microbiol. 12:1377–1383.
Palleroni NJ. 2008. The road to the taxonomy of Pseudomonas, p 1–18. In Cornelis P (ed), Pseudomonas. Genomics and molecular biology. Caister Academic Press, Norfolk, United Kingdom.
Moore ERB, Mau M, Arnscheidt A, Bottger EC, Hutson RA, Collins MD, Peer YVD, Wachter RD, and Timmis KN. 1996. The determination and comparison of the 16S rRNA gene sequences of species of the genus Pseudomonas (sensu stricto) and estimation of the natural intrageneric relationships. Syst. Appl. Microbiol. 1:478–492.
Yamamoto S, Kasai H, Arnold DL, Jackson RW, Vivian A, and Harayama S. 2000. Phylogeny of the genus Pseudomonas: intrageneric structure reconstructed from the nucleotide sequences of gyrB and rpoD genes. Microbiology 146:2385–2394.
Urwin R and Maiden MC. 2003. Multi-locus sequence typing: a tool for global epidemiology. Trends Microbiol. 11:479–487.
Chan MS, Maiden MC, and Spratt BG. 2001. Database-driven multi locus sequence typing (MLST) of bacterial pathogens. Bioinformatics 17:1077–1083.
Sullivan CB, Diggle MA, and Clarke SC. 2005. Multilocus sequence typing: data analysis in clinical microbiology and public health. Mol. Biotechnol. 29:245–254.
Byun R, Elbourne LD, Lan R, and Reeves PR. 1999. Evolutionary relationships of pathogenic clones of Vibrio cholerae by sequence analysis of four housekeeping genes. Infect. Immun. 67:1116–1124.
Savli H, Karadenizli A, Kolayli F, Gundes S, Ozbek U, and Vahaboglu H. 2003. Expression stability of six housekeeping genes: a proposal for resistance gene quantification studies of Pseudomonas aeruginosa by real-time quantitative RT-PCR. J. Med. Microbiol. 52:403–408.
Dagerhamn J, Blomberg C, Browall S, Sjostrom K, Morfeldt E, and Henriques-Normark B. 2008. Determination of accessory gene patterns predicts the same relatedness among strains of Streptococcus pneumoniae as sequencing of housekeeping genes does and represents a novel approach in molecular epidemiology. J. Clin. Microbiol. 46:863–868.
Adekambi T, Drancourt M, and Raoult D. 2009. The rpoB gene as a tool for clinical microbiologists. Trends Microbiol. 17:37–45.
Tayeb LA, Lefevre M, Passet V, Diancourt L, Brisse S, and Grimont PA. 2008. Comparative phylogenies of Burkholderia, Ralstonia, Comamonas, Brevundimonas and related organisms derived from rpoB, gyrB and rrs gene sequences. Res. Microbiol. 159:169–177.
van Passel MW, Kuramae EE, Luyf AC, Bart A, and Boekhout T. 2006. The reach of the genome signature in prokaryotes. BMC Evol. Biol. 6:84.
Goris J, Konstantinidis KT, Klappenbach JA, Coenye T, Vandamme P, and Tiedje JM. 2007. DNA-DNA hybridization values and their relationship to whole-genome sequence similarities. Int. J. Syst. Evol. Microbiol. 57:81–91.
Pearson WR. 2014. BLAST and FASTA similarity searching for multiple sequence alignment. Methods Mol. Biol. 1079:75–101.
Salmond GP and Reeves PJ. 1993. Membrane traffic wardens and protein secretion in gram-negative bacteria. Trends Biochem. Sci. 18:7–12.
Cornelis P. 2010. Iron uptake and metabolism in pseudomonads. Appl. Microbiol. Biotechnol. 86:1637–1645.
Cornelis P, Matthijs S, and Van Oeffelen L. 2009. Iron uptake regulation in Pseudomonas aeruginosa. Biometals 22:15–22.
Katoh K and Standley DM. 2013. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 30:772–780.
Katoh K and Frith MC. 2012. Adding unaligned sequences into an existing alignment using MAFFT and LAST. Bioinformatics 28:3144–3146.
Katoh K, Kuma K, Toh H, and Miyata T. 2005. MAFFT version 5: improvement in accuracy of multiple sequence alignment. Nucleic Acids Res. 33:511–518.
Katoh K, Misawa K, Kuma K, and Miyata T. 2002. MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res. 30:3059–3066.
Botha P, Archer L, Anderson RL, Lordan J, Dark JH, Corris PA, Gould K, and Fisher AJ. 2008. Pseudomonas aeruginosa colonization of the allograft after lung transplantation and the risk of bronchiolitis obliterans syndrome. Transplantation 85:771–774.
Vos R, Vanaudenaerde BM, Geudens N, Dupont LJ, Van Raemdonck DE, and Verleden GM. 2008. Pseudomonal airway colonisation: risk factor for bronchiolitis obliterans syndrome after lung transplantation? Eur. Respir. J. 31:1037–1045.
Gottlieb J, Mattner F, Weissbrodt H, Dierich M, Fuehner T, Strueber M, Simon A, and Welte T. 2009. Impact of graft colonization with gram-negative bacteria after lung transplantation on the development of bronchiolitis obliterans syndrome in recipients with cystic fibrosis. Respir. Med. 103:743–749.
Willner DL, Hugenholtz P, Yerkovich ST, Tan ME, Daly JN, Lachner N, Hopkins PM, and Chambers DC. 2013. Reestablishment of recipient-associated microbiota in the lung allograft is linked to reduced risk of bronchiolitis obliterans syndrome. Am. J. Respir. Crit. Care Med. 187:640–647.
Enderby B, Smith D, Carroll W, and Lenney W. 2009. Hydrogen cyanide as a biomarker for Pseudomonas aeruginosa in the breath of children with cystic fibrosis. Pediatr. Pulmonol. 44:142–147.
Laville J, Blumer C, Von Schroetter C, Gaia V, Defago G, Keel C, and Haas D. 1998. Characterization of the hcnABC gene cluster encoding hydrogen cyanide synthase and anaerobic regulation by ANR in the strictly aerobic biocontrol agent Pseudomonas fluorescens CHA0. J. Bacteriol. 180:3187–3196.
Partida-Martinez LP and Hertweck C. 2005. Pathogenic fungus harbours endosymbiotic bacteria for toxin production. Nature 437:884–888.
Tekeda R. 1958. Pseudomonas pigments. I. Pyoluteorin, a new chlorine-containing pigment produced by Pseudomonas aeruginosa. Hakko Kogaku Zasshi 36:281–290.
Ligon JM, Hill DS, Hammer PE, Torkewitz NR, Hofmann D, Kempf H, and Pee H. 2000. Natural products with antifungal activity from Pseudomonas biocontrol bacteria. Pest Manag. Sci. 56:688–695.
Hothersall J, Wu J, Rahman AS, Shields JA, Haddock J, Johnson N, Cooper SM, Stephens ER, Cox RJ, Crosby J, Willis CL, Simpson TJ, and Thomas CM. 2007. Mutational analysis reveals that all tailoring region genes are required for production of polyketide antibiotic mupirocin by Pseudomonas fluorescens: pseudomonic acid B biosynthesis precedes pseudomonic acid A. J. Biol. Chem. 282:15451–15461.
Sutherland R, Boon RJ, Griffin KE, Masters PJ, Slocombe B, and White AR. 1985. Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use. Antimicrob. Agents Chemother. 27:495–498.
Villiger JW, Robertson WD, Kanji K, Ah Chan M, Fetherston J, Hague IK, Haycock D, and Hunter P. 1986. A comparison of the new topical antibiotic mupirocin (‘Bactroban') with oral antibiotics in the treatment of skin infections in general practice. Curr. Med. Res. Opin. 10:339–345.
Odom RB. 1989. Mupirocin (2 percent) ointment in the treatment of primary and secondary skin infections. Cutis 43:599–601.
Mertz PM, Marshall DA, Eaglstein WH, Piovanetti Y, and Montalvo J. 1989. Topical mupirocin treatment of impetigo is equal to oral erythromycin therapy. Arch. Dermatol. 125:1069–1073.
Yanagisawa T, Lee JT, Wu HC, and Kawakami M. 1994. Relationship of protein structure of isoleucyl-tRNA synthetase with pseudomonic acid resistance of Escherichia coli. A proposed mode of action of pseudomonic acid as an inhibitor of isoleucyl-tRNA synthetase. J. Biol. Chem. 269:24304–24309.
Hughes J and Mellows G. 1978. On the mode of action of pseudomonic acid: inhibition of protein synthesis in Staphylococcus aureus. J. Antibiot. (Tokyo) 31:330–335.
Hughes J and Mellows G. 1980. Interaction of pseudomonic acid A with Escherichia coli B isoleucyl-tRNA synthetase. Biochem. J. 191:209–219.
Hughes J, Mellows G, and Soughton S. 1980. How does Pseudomonas fluorescens, the producing organism of the antibiotic pseudomonic acid A, avoid suicide? FEBS Lett. 122:322–324.
Hohnadel D and Meyer JM. 1988. Specificity of pyoverdine-mediated iron uptake among fluorescent Pseudomonas strains. J. Bacteriol. 170:4865–4873.
Mossialos D, Meyer JM, Budzikiewicz H, Wolff U, Koedam N, Baysse C, Anjaiah V, and Cornelis P. 2000. Quinolobactin, a new siderophore of Pseudomonas fluorescens ATCC 17400, the production of which is repressed by the cognate pyoverdine. Appl. Environ. Microbiol. 66:487–492.
Mercado-Blanco J, van der Drift KM, Olsson PE, Thomas-Oates JE, van Loon LC, and Bakker PA. 2001. Analysis of the pmsCEAB gene cluster involved in biosynthesis of salicylic acid and the siderophore pseudomonine in the biocontrol strain Pseudomonas fluorescens WCS374. J. Bacteriol. 183:1909–1920.
Gennari M and Dragotto F. 1992. A study of the incidence of different fluorescent Pseudomonas species and biovars in the microflora of fresh and spoiled meat and fish, raw milk, cheese, soil and water. J. Appl. Bacteriol. 72:281–288.
Andreani NA, Martino ME, Fasolato L, Carraro L, Montemurro F, Mioni R, Bordin P, and Cardazzo B. 2014. Tracking the blue: a MLST approach to characterise the Pseudomonas fluorescens group. Food Microbiol. 39:116–126.
Lau GW, Hassett DJ, Ran H, and Kong F. 2004. The role of pyocyanin in Pseudomonas aeruginosa infection. Trends Mol. Med. 10:599–606.
Laville J, Voisard C, Keel C, Maurhofer M, Defago G, and Haas D. 1992. Global control in Pseudomonas fluorescens mediating antibiotic synthesis and suppression of black root rot of tobacco. Proc. Natl. Acad. Sci. U. S. A. 89:1562–1566.
Maurhofer M, Reimmann C, Schmidli-Sacherer P, Heeb S, Haas D, and Defago G. 1998. Salicylic acid biosynthetic genes expressed in Pseudomonas fluorescens strain P3 improve the induction of systemic resistance in tobacco against tobacco necrosis virus. Phytopathology 88:678–684.
Sacherer P, Defago G, and Haas D. 1994. Extracellular protease and phospholipase C are controlled by the global regulatory gene gacA in the biocontrol strain Pseudomonas fluorescens CHA0. FEMS Microbiol. Lett. 116:155–160.
Schnider-Keel U, Seematter A, Maurhofer M, Blumer C, Duffy B, Gigot-Bonnefoy C, Reimmann C, Notz R, Defago G, Haas D, and Keel C. 2000. Autoinduction of 2,4-diacetylphloroglucinol biosynthesis in the biocontrol agent Pseudomonas fluorescens CHA0 and repression by the bacterial metabolites salicylate and pyoluteorin. J. Bacteriol. 182:1215–1225.
Pessi G and Haas D. 2001. Dual control of hydrogen cyanide biosynthesis by the global activator GacA in Pseudomonas aeruginosa PAO1. FEMS Microbiol. Lett. 200:73–78.
Reimmann C, Beyeler M, Latifi A, Winteler H, Foglino M, Lazdunski A, and Haas D. 1997. The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase. Mol. Microbiol. 24:309–319.
Heeb S, Blumer C, and Haas D. 2002. Regulatory RNA as mediator in GacA/RsmA-dependent global control of exoproduct formation in Pseudomonas fluorescens CHA0. J. Bacteriol. 184:1046–1056.
Argaman L, Hershberg R, Vogel J, Bejerano G, Wagner EG, Margalit H, and Altuvia S. 2001. Novel small RNA-encoding genes in the intergenic regions of Escherichia coli. Curr. Biol. 11:941–950.
Wassarman KM. 2002. Small RNAs in bacteria: diverse regulators of gene expression in response to environmental changes. Cell 109:141–144.
Storz G. 2002. An expanding universe of noncoding RNAs. Science 296:1260–1263.
Wagner EG, Altuvia S, and Romby P. 2002. Antisense RNAs in bacteria and their genetic elements. Adv. Genet. 46:361–398.
Bassler BL. 2002. Small talk. Cell-to-cell communication in bacteria. Cell 109:421–424.
Fuqua WC, Winans SC, and Greenberg EP. 1994. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J. Bacteriol. 176:269–275.
Daneshvar A and Truelstrup H. 2013. Kinetics of biofilm formation and desiccation survival of Listeria monocytogenes in single and dual species biofilms with Pseudomonas fluorescens, Serratia proteamaculans or Shewanella baltica on food-grade stainless steel surfaces. Biofouling 29:1253–1268.
Ude S, Arnold DL, Moon CD, Timms-Wilson T, and Spiers AJ. 2006. Biofilm formation and cellulose expression among diverse environmental Pseudomonas isolates. Environ. Microbiol. 8:1997–2011.
Bloemberg GV and Lugtenberg BJ. 2001. Molecular basis of plant growth promotion and biocontrol by rhizobacteria. Curr. Opin. Plant Biol. 4:343–350.
Whitehead NA, Barnard AM, Slater H, Simpson NJ, and Salmond GP. 2001. Quorum-sensing in Gram-negative bacteria. FEMS Microbiol. Rev. 25:365–404.
El-Sayed AK, Hothersall J, and Thomas CM. 2001. Quorum-sensing-dependent regulation of biosynthesis of the polyketide antibiotic mupirocin in Pseudomonas fluorescens NCIMB 10586. Microbiology 147:2127–2139.
Laue BE, Jiang Y, Chhabra SR, Jacob S, Stewart GS, Hardman A, Downie JA, O'Gara F, and Williams P. 2000. The biocontrol strain Pseudomonas fluorescens F113 produces the Rhizobium small bacteriocin, N-(3-hydroxy-7-cis-tetradecenoyl)homoserine lactone, via HdtS, a putative novel N-acylhomoserine lactone synthase. Microbiology 146:2469–2480.
Navarro MV, Newell PD, Krasteva PV, Chatterjee D, Madden DR, O'Toole GA, and Sondermann H. 2011. Structural basis for c-di-GMP-mediated inside-out signaling controlling periplasmic proteolysis. PLoS Biol. 9:e1000588.
Newell PD, Yoshioka S, Hvorecny KL, Monds RD, and O'Toole GA. 2011. Systematic analysis of diguanylate cyclases that promote biofilm formation by Pseudomonas fluorescens Pf0-1. J. Bacteriol. 193:4685–4698.
Newell PD, Boyd CD, Sondermann H, and O'Toole GA. 2011. A c-di-GMP effector system controls cell adhesion by inside-out signaling and surface protein cleavage. PLoS Biol. 9:e1000587.
Rosqvist R, Magnusson KE, and Wolf-Watz H. 1994. Target cell contact triggers expression and polarized transfer of Yersinia YopE cytotoxin into mammalian cells. EMBO J. 13:964–972.
Sory MP and Cornelis GR. 1994. Translocation of a hybrid YopE-adenylate cyclase from Yersinia enterocolitica into HeLa cells. Mol. Microbiol. 14:583–594.
He SY, Nomura K, and Whittam TS. 2004. Type III protein secretion mechanism in mammalian and plant pathogens. Biochim. Biophys. Acta 1694:181–206.
Lindgren PB, Peet RC, and Panopoulos NJ. 1986. Gene cluster of Pseudomonas syringae pv. “phaseolicola” controls pathogenicity of bean plants and hypersensitivity of nonhost plants. J. Bacteriol. 168:512–522.
Gopalan S, Wei W, and He SY. 1996. hrp gene-dependent induction of hin1: a plant gene activated rapidly by both harpins and the avrPto gene-mediated signal. Plant J. 10:591–600.
Tang X, Frederick RD, Zhou J, Halterman DA, Jia Y, and Martin GB. 1996. Initiation of plant disease resistance by physical interaction of AvrPto and Pto kinase. Science 274:2060–2063.
Scofield SR, Tobias CM, Rathjen JP, Chang JH, Lavelle DT, Michelmore RW, and Staskawicz BJ. 1996. Molecular basis of gene-for-gene specificity in bacterial speck disease of tomato. Science 274:2063–2065.
Leister RT, Ausubel FM, and Katagiri F. 1996. Molecular recognition of pathogen attack occurs inside of plant cells in plant disease resistance specified by the Arabidopsis genes RPS2 and RPM1. Proc. Natl. Acad. Sci. U. S. A. 93:15497–15502.
Ma Q, Zhai Y, Schneider JC, Ramseier TM, and Saier MH Jr. 2003. Protein secretion systems of Pseudomonas aeruginosa and P. fluorescens. Biochim. Biophys. Acta 1611:223–233.
Rainey PB. 1999. Adaptation of Pseudomonas fluorescens to the plant rhizosphere. Environ. Microbiol. 1:243–257.
Jackson RW, Preston GM, and Rainey PB. 2005. Genetic characterization of Pseudomonas fluorescens SBW25 rsp gene expression in the phytosphere and in vitro. J. Bacteriol. 187:8477–8488.
Vinatzer BA, Jelenska J, and Greenberg JT. 2005. Bioinformatics correctly identifies many type III secretion substrates in the plant pathogen Pseudomonas syringae and the biocontrol isolate P. fluorescens SBW25. Mol. Plant Microbe Interact. 18:877–888.
Engel J and Balachandran P. 2009. Role of Pseudomonas aeruginosa type III effectors in disease. Curr. Opin. Microbiol. 12:61–66.
Shanahan P, O'Sullivan DJ, Simpson P, Glennon JD, and O'Gara F. 1992. Isolation of 2,4-diacetylphloroglucinol from a fluorescent pseudomonad and investigation of physiological parameters influencing its production. Appl. Environ. Microbiol. 58:353–358.
Cronin D, Moenne-Loccoz Y, Fenton A, Dunne C, Dowling DN, and O'Gara F. 1997. Role of 2,4-diacetylphloroglucinol in the interactions of the biocontrol pseudomonad strain F113 with the potato cyst nematode Globodera rostochiensis. Appl. Environ. Microbiol. 63:1357–1361.
Barahona E, Navazo A, Martinez-Granero F, Zea-Bonilla T, Perez-Jimenez RM, Martin M, and Rivilla R. 2011. Pseudomonas fluorescens F113 mutant with enhanced competitive colonization ability and improved biocontrol activity against fungal root pathogens. Appl. Environ. Microbiol. 77:5412–5419.
Fenton AM, Stephens PM, Crowley J, O'Callaghan M, and O'Gara F. 1992. Exploitation of gene(s) involved in 2,4-diacetylphloroglucinol biosynthesis to confer a new biocontrol capability to a Pseudomonas strain. Appl. Environ. Microbiol. 58:3873–3878.
Pernthaler J. 2005. Predation on prokaryotes in the water column and its ecological implications. Nat. Rev. Microbiol. 3:537–546.
Neidig N, Paul RJ, Scheu S, and Jousset A. 2011. Secondary metabolites of Pseudomonas fluorescens CHA0 drive complex non-trophic interactions with bacterivorous nematodes. Microb. Ecol. 61:853–859.
Chauhan A, Layton AC, Williams DE, Smartt AE, Ripp S, Karpinets TV, Brown SD, and Sayler GS. 2011. Draft genome sequence of the polycyclic aromatic hydrocarbon-degrading, genetically engineered bioluminescent bioreporter Pseudomonas fluorescens HK44. J. Bacteriol. 193:5009–5010.
Madi A, Lakhdari O, Blottiere HM, Guyard-Nicodeme M, Le Roux K, Groboillot A, Svinareff P, Dore J, Orange N, Feuilloley MG, and Connil N. 2010. The clinical Pseudomonas fluorescens MFN1032 strain exerts a cytotoxic effect on epithelial intestinal cells and induces interleukin-8 via the AP-1 signaling pathway. BMC Microbiol. 10:215.
Choi HJ, Seo CH, Park SH, Yang H, Do KH, Kim J, Kim HK, Chung DH, Ahn JH, and Moon Y. 2011. Involvement of epidermal growth factor receptor-linked signaling responses in Pseudomonas fluorescens-infected alveolar epithelial cells. Infect. Immun. 79:1998–2005.
Hirvonen MR, Huttunen K, and Roponen M. 2005. Bacterial strains from moldy buildings are highly potent inducers of inflammatory and cytotoxic effects. Indoor Air 15(Suppl 9):S65–S70.
Richard A, Rossignol G, Comet JP, Bernot G, Guespin-Michel J, and Merieau A. 2012. Boolean models of biosurfactants production in Pseudomonas fluorescens. PLoS One 7:e24651.
Rossignol G, Merieau A, Guerillon J, Veron W, Lesouhaitier O, Feuilloley MG, and Orange N. 2008. Involvement of a phospholipase C in the hemolytic activity of a clinical strain of Pseudomonas fluorescens. BMC Microbiol. 8:189.
Sperandio D, Rossignol G, Guerillon J, Connil N, Orange N, Feuilloley MG, and Merieau A. 2010. Cell-associated hemolysis activity in the clinical strain of Pseudomonas fluorescens MFN1032. BMC Microbiol. 10:124.
Dacheux D, Goure J, Chabert J, Usson Y, and Attree I. 2001. Pore-forming activity of type III system-secreted proteins leads to oncosis of Pseudomonas aeruginosa-infected macrophages. Mol. Microbiol. 40:76–85.
Raaijmakers JM, De Bruijn I, Nybroe O, and Ongena M. 2010. Natural functions of lipopeptides from Bacillus and Pseudomonas: more than surfactants and antibiotics. FEMS Microbiol. Rev. 34:1037–1062.
Hallet B. 2001. Playing Dr Jekyll and Mr Hyde: combined mechanisms of phase variation in bacteria. Curr. Opin. Microbiol. 4:570–581.
Hogardt M and Heesemann J. 2013. Microevolution of Pseudomonas aeruginosa to a chronic pathogen of the cystic fibrosis lung. Curr. Top. Microbiol. Immunol. 358:91–118.
Anderson M and Davey R. 1994. Pseudobacteraemia with Pseudomonas fluorescens. Med. J. Aust. 160:233–234.
Collignon P, Dreimanis D, and Beckingham W. 1999. Pseudobacteraemia due to Pseudomonas fluorescens. J. Hosp. Infect. 43:321–322.
Gottlieb T, Funnell G, and Gosbell I. 1991. Pseudomonas fluorescens pseudobacteraemia. Med. J. Aust. 155:854–855.
Namnyak S, Hussain S, Davalle J, Roker K, and Strickland M. 1999. Contaminated lithium heparin bottles as a source of pseudobacteraemia due to Pseudomonas fluorescens. J. Hosp. Infect. 41:23–28.
Siebor E, Llanes C, Lafon I, Ogier-Desserrey A, Duez JM, Pechinot A, Caillot D, Grandjean M, Sixt N, and Neuwirth C. 2007. Presumed pseudobacteremia outbreak resulting from contamination of proportional disinfectant dispenser. Eur. J. Clin. Microbiol. Infect. Dis. 26:195–198.
Simor AE, Ricci J, Lau A, Bannatyne RM, and Ford-Jones L. 1985. Pseudobacteremia due to Pseudomonas fluorescens. Pediatr. Infect. Dis. 4:508–512.
Smith J, Ashhurst-Smith C, and Norton R. 2002. Pseudomonas fluorescens pseudobacteraemia: a cautionary lesson. J. Paediatr. Child Health 38:63–65.
Whyte A, Lafong C, Malone J, and Golda BP. 1999. Contaminated lithium heparin bottles as a source of pseudobacteraemia. J. Hosp. Infect. 42:342–343.
Adeyemi AI, Sulaiman AA, Solomon BB, Chinedu OA, and Victor IA. 2010. Bacterial bloodstream infections in HIV-infected adults attending a Lagos teaching hospital. J. Health Popul. Nutr. 28:318–326.
Bompard Y, Lambert T, Gantzer A, Chastel A, Voinnesson A, and Aufrant C. 1988. Use of imipenem-cilastatin in neonatal septicemias caused by gram-negative bacilli multiresistant to beta-lactam antibiotics. Pathol. Biol. (Paris) 36:521–524.
Popov DA and Vostrikova T. 2011. The first experience of application of PCR techniques in real-time mode to diagnose bacteremia during postoperational period in cardiosurgery patients. Klin. Lab. Diagn. 2011:49–52.
Rais-Bahrami K, Platt P, and Naqvi M. 1990. Neonatal pseudomonas sepsis: even early diagnosis is too late. Clin. Pediatr. (Phila.) 29:444.
Rodriguez Ramirez J, Pena Quintana P, Cabrera Galvan JJ, and Gomez Diaz J. 1989. Severe intrahepatic cholestasis in sepsis caused by Pseudomonas fluorescens. Rev. Clin. Esp. 185:106–107.
Shah SS, Kagen J, Lautenbach E, Bilker WB, Matro J, Dominguez TE, Tabbutt S, Gaynor JW, and Bell LM. 2007. Bloodstream infections after median sternotomy at a children's hospital. J. Thorac. Cardiovasc. Surg. 133:435–440.
Sutter VL. 1968. Identification of Pseudomonas species isolated from hospital environment and human sources. Appl. Microbiol. 16:1532–1538.
Brook I. 1987. Microbiology of human and animal bite wounds in children. Pediatr. Infect. Dis. J. 6:29–32.
Dalamaga M, Karmaniolas K, Chavelas C, Liatis S, Matekovits H, and Migdalis I. 2005. Pseudomonas fluorescens cutaneous abscess and recurrent bacteremia following a dog bite. Int. J. Dermatol. 44:347–349.
Carpenter EM and Dicks D. 1982. Isolation of Pseudomonas fluorescens after suprapubic catheterisation. J. Clin. Pathol. 35:581.
Pappas G, Karavasilis V, Christou L, and Tsianos EV. 2006. Pseudomonas fluorescens infections in clinical practice. Scand. J. Infect. Dis. 38:68–70.
Rutenburg AM, Koota GM, and Schweinburg FB. 1958. The efficacy of kanamycin in the treatment of surgical infections. Ann. N. Y. Acad. Sci. 76:348–362.
Redding PJ and McWalter PW. 1980. Pseudomonas fluorescens cross-infection due to contaminated humidifier water. Br. Med. J. 281:275.
Thangkhiew I. 1986. Successful treatment with ceftazidime of a Pseudomonas fluorescens chest infection in a myasthenic patient. J. Antimicrob. Chemother. 18:428–429.
Zervos M and Nelson M. 1998. Cefepime versus ceftriaxone for empiric treatment of hospitalized patients with community-acquired pneumonia. The Cefepime Study Group. Antimicrob. Agents Chemother. 42:729–733.
Bahrani-Mougeot FK, Paster BJ, Coleman S, Barbuto S, Brennan MT, Noll J, Kennedy T, Fox PC, and Lockhart PB. 2007. Molecular analysis of oral and respiratory bacterial species associated with ventilator-associated pneumonia. J. Clin. Microbiol. 45:1588–1593.
Klinger JD and Thomassen MJ. 1985. Occurrence and antimicrobial susceptibility of gram-negative nonfermentative bacilli in cystic fibrosis patients. Diagn. Microbiol. Infect. Dis. 3:149–158.
Sutton CL, Kim J, Yamane A, Dalwadi H, Wei B, Landers C, Targan SR, and Braun J. 2000. Identification of a novel bacterial sequence associated with Crohn's disease. Gastroenterology 119:23–31.
Dalwadi H, Wei B, Kronenberg M, Sutton CL, and Braun J. 2001. The Crohn's disease-associated bacterial protein I2 is a novel enteric T cell superantigen. Immunity 15:149–158.
Fukata M, Michelsen KS, Eri R, Thomas LS, Hu B, Lukasek K, Nast CC, Lechago J, Xu R, Naiki Y, Soliman A, Arditi M, and Abreu MT. 2005. Toll-like receptor-4 is required for intestinal response to epithelial injury and limiting bacterial translocation in a murine model of acute colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 288:G1055–G1065.
Wei B, Huang T, Dalwadi H, Sutton CL, Bruckner D, and Braun J. 2002. Pseudomonas fluorescens encodes the Crohn's disease-associated I2 sequence and T-cell superantigen. Infect. Immun. 70:6567–6575.
Ashorn S, Raukola H, Valineva T, Ashorn M, Wei B, Braun J, Rantala I, Kaukinen K, Luukkaala T, Collin P, Maki M, and Iltanen S. 2008. Elevated serum anti-Saccharomyces cerevisiae, anti-I2 and anti-OmpW antibody levels in patients with suspicion of celiac disease. J. Clin. Immunol. 28:486–494.
Ashorn S, Valineva T, Kaukinen K, Ashorn M, Braun J, Raukola H, Rantala I, Collin P, Maki M, Luukkaala T, and Iltanen S. 2009. Serological responses to microbial antigens in celiac disease patients during a gluten-free diet. J. Clin. Immunol. 29:190–195.
Mundwiler ML, Mei L, Landers CJ, Reveille JD, Targan S, and Weisman MH. 2009. Inflammatory bowel disease serologies in ankylosing spondylitis patients: a pilot study. Arthritis Res. Ther. 11:R177.
Yu JE, De Ravin SS, Uzel G, Landers C, Targan S, Malech HL, Holland SM, Cao W, Harpaz N, Mayer L, and Cunningham-Rundles C. 2011. High levels of Crohn's disease-associated anti-microbial antibodies are present and independent of colitis in chronic granulomatous disease. Clin. Immunol. 138:14–22.
Silby MW, Winstanley C, Godfrey SA, Levy SB, and Jackson RW. 2011. Pseudomonas genomes: diverse and adaptable. FEMS Microbiol. Rev. 35:652–680.
Katoh K and Toh H. 2008. Recent developments in the MAFFT multiple sequence alignment program. Brief. Bioinform. 9:286–298.
Kuraku S, Zmasek CM, Nishimura O, and Katoh K. 2013. aLeaves facilitates on-demand exploration of metazoan gene family trees on MAFFT sequence alignment server with enhanced interactivity. Nucleic Acids Res. 41:W22–W28.
Han MV and Zmasek CM. 2009. phyloXML: XML for evolutionary biology and comparative genomics. BMC Bioinformatics 10:356.
Jumpstart Consortium Human Microbiome Project Data Generation Working Group. 2012. Evaluation of 16S rDNA-based community profiling for human microbiome research. PLoS One 7:e39315.
Dubey L, Krasinski K, and Hernanz-Schulman M. 1988. Osteomyelitis secondary to trauma or infected contiguous soft tissue. Pediatr. Infect. Dis. J. 7:26–34.
Hessen MT, Ingerman MJ, Kaufman DH, Weiner P, Santoro J, Korzeniowski OM, Boscia J, Topiel M, Bush LM, and Kaye D. 1987. Clinical efficacy of ciprofloxacin therapy for gram-negative bacillary osteomyelitis. Am. J. Med. 82:262–265.
Laguna del Estal P, Castaneda Pastor A, Lopez-Cano Gomez M, and Garcia Montero P. 2010. Bacterial meningitis secondary to spinal analgesia and anaesthesia. Neurologia 25:552–556.
Essex RW, Charles PG, and Allen PJ. 2004. Three cases of post-traumatic endophthalmitis caused by unusual bacteria. Clin. Exp. Ophthalmol. 32:445–447.
Kitzmann AS, Goins KM, Syed NA, and Wagoner MD. 2008. Bilateral herpes simplex keratitis with unilateral secondary bacterial keratitis and corneal perforation in a patient with pityriasis rubra pilaris. Cornea 27:1212–1214.
Ye JJ, Guo LB, Wang SR, Wang WW, and Min HY. 2012. Vitreal surgery and etiological diagnosis of bacterial endophthalmitis. Zhonghua Yan Ke Za Zhi 48:995–1000.
Olszewski J and Milonski J. 2008. The analysis of the bacterial and fungal flora in maxillary sinuses in patients operated due to FESS method. Otolaryngol. Pol. 62:458–461.
Foulon W, Naessens A, Lauwers S, Volckaert M, Devroey P, and Amy JJ. 1981. Pelvic inflammatory disease due to Pseudomonas fluorescens in patient wearing an intrauterine device. Lancet ii:358–359.
Compeau G, Al-Achi BJ, Platsouka E, and Levy SB. 1988. Survival of rifampin-resistant mutants of Pseudomonas fluorescens and Pseudomonas putida in soil systems. Appl. Environ. Microbiol. 54:2432–2438.
Wilson M and Lindow SE. 1994. Ecological similarity and coexistence of epiphytic Ice-nucleating (Ice) Pseudomonas syringae strains and a non-Ice-nucleating (Ice) biological control agent. Appl. Environ. Microbiol. 60:3128–3137.
Pierson EA and Weller DM. 1994. Use of mixtures of fluorescent pseudomonads to suppress take-all and improve the growth of wheat. Phytopathology 84:940–947.
Raaijmakers JM and Weller DM. 1998. Natural plant protection by 2,4-diacetylphloroglucinol-producing Pseudomonas spp. in take-all decline soils. Mol. Plant Microbe Interact. 11:144–152.
Banowetz GM, Azevedo MD, Armstrong DJ, Halgren AB, and Mills DI. 2008. Germination-arrest factor (GAF): biological properties of a novel, naturally-occurring herbicide produced by selected isolates of rhizosphere bacteria. Biol. Control 46:380–390.
Kimbrel JA, Givan SA, Halgren AB, Creason AL, Mills DI, Banowetz GM, Armstrong DJ, and Chang JH. 2010. An improved, high-quality draft genome sequence of the germination-arrest factor-producing Pseudomonas fluorescens WH6. BMC Genomics 11:522.
Barton MD, Petronio M, Giarrizzo JG, Bowling BV, and Barton HA. 2013. The genome of Pseudomonas fluorescens strain R124 demonstrates phenotypic adaptation to the mineral environment. J. Bacteriol. 195:4793–4803.
Paulsen IT, Press CM, Ravel J, Kobayashi DY, Myers GS, Mavrodi DV, DeBoy RT, Seshadri R, Ren Q, Madupu R, Dodson RJ, Durkin AS, Brinkac LM, Daugherty SC, Sullivan SA, Rosovitz MJ, Gwinn ML, Zhou L, Schneider DJ, Cartinhour SW, Nelson WC, Weidman J, Watkins K, Tran K, Khouri H, Pierson EA, Pierson LS 3rd, Thomashow LS, and Loper JE. 2005. Complete genome sequence of the plant commensal Pseudomonas fluorescens Pf-5. Nat. Biotechnol. 23:873–878.
Stutz EW, Défago G, and Kern H. 1986. Naturally occurring fluorescent pseudomonads involved in suppression of black root rot of tobacco. Phytopathology 76:181–185.
Ramette A, Frapolli M, Fischer-Le Saux M, Gruffaz C, Meyer JM, Defago G, Sutra L, and Moenne-Loccoz Y. 2011. Pseudomonas protegens sp. nov., widespread plant-protecting bacteria producing the biocontrol compounds 2,4-diacetylphloroglucinol and pyoluteorin. Syst. Appl. Microbiol. 34:180–188.
Ortet P, Barakat M, Lalaouna D, Fochesato S, Barbe V, Vacherie B, Santaella C, Heulin T, and Achouak W. 2011. Complete genome sequence of a beneficial plant root-associated bacterium, Pseudomonas brassicacearum. J. Bacteriol. 193:3146.
Harris R and Knowles CJ. 1983. Isolation and growth of a Pseudomonas species that utilizes cyanide as a source of nitrogen. J. Gen. Microbiol. 129:1005–1011.
Vilo CA, Benedik MJ, Kunz DA, and Dong Q. 2012. Draft genome sequence of the cyanide-utilizing bacterium Pseudomonas fluorescens strain NCIMB 11764. J. Bacteriol. 194:6618–6619.
Kropp BR, Thomas E, Pounder JI, and Anderson AJ. 1996. Increased emergence of spring wheat after inoculation with Pseudomonas chlororaphis isolate 2E3 under field and laboratory conditions. Biol. Fertil. Soils 23:200–206.
Kluepfel DA, McInnis TM, and Zehr EI. 1993. Involvement of root-colonizing bacteria in peach orchard soils suppressive of the nematode Criconemella xenoplax. Phytopathology 83:1240–1245.

Author Bios

Brittan S. Scales
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
Brittan S. Scales received her Master's in Public Health in Infectious Diseases and Vaccinology from the University of Berkeley, Berkeley, CA. She is currently a Ph.D. candidate in Microbiology and Immunology at the University of Michigan, Ann Arbor, MI. Her thesis work and research interests include understanding the lung microbiome in relation to chronic lung disease and comparative genomics of Pseudomonas bacteria found in the mammalian respiratory tract.
Robert P. Dickson
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
Robert P. Dickson, M.D., received his medical education from Duke University and completed a residency and chief residency in Internal Medicine at the University of Washington. He is currently a Fellow in Pulmonary and Critical Care Medicine at the University of Michigan and studies the pathogenesis of bacterial pneumonia and the impact of the lung microbiome on respiratory health.
John J. LiPuma
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA
John J. LiPuma received his M.D. from St. Louis University Medical School and has held faculty positions at Drexel University and the University of Michigan. He holds the James L. Wilson, M.D., Endowed Research Chair and is a Professor of Pediatrics and Communicable Diseases at the University of Michigan Medical School, as well as Professor of Epidemiology, School of Public Health. His research interests for the past 2 decades have included Pseudomonas and Burkholderia infections in cystic fibrosis, the population genetic structure and evolution of the Burkholderia cepacia complex in cystic fibrosis, virulence factors and pathogenic mechanisms of the B. cepacia complex and related species, and microbiome community dynamics during cystic fibrosis.
Gary B. Huffnagle [email protected]
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
Gary B. Huffnagle received his Ph.D. in Immunology from the University of Texas Southwestern Medical School and has spent his faculty career at the University of Michigan. He is a Professor of Pulmonary and Critical Care Medicine and Professor of Microbiology and Immunology at the University of Michigan Medical School. He is also a member of the American Academy of Microbiology. His research interests for the past 2 decades have included the interaction between opportunistic fungal pathogens, the fungal and bacterial microbiomes, and the immune system during respiratory disease. Over the past 5 years, he has developed interests in the ecology of the human lung microbiome during health and respiratory disease, including the role of the Pseudomonas genus in lung health and disease.

Information & Contributors


Published In

cover image Clinical Microbiology Reviews
Clinical Microbiology Reviews
Volume 27Number 4October 2014
Pages: 927 - 948
PubMed: 25278578


Published online: 1 October 2014


Request permissions for this article.



Brittan S. Scales
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
Robert P. Dickson
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
John J. LiPuma
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA
Gary B. Huffnagle [email protected]
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA

Metrics & Citations


Note: There is a 3- to 4-day delay in article usage, so article usage will not appear immediately after publication.

Citation counts come from the Crossref Cited by service.


If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

View Options

Figures and Media






Share the article link

Share with email

Email a colleague

Share on social media

American Society for Microbiology ("ASM") is committed to maintaining your confidence and trust with respect to the information we collect from you on websites owned and operated by ASM ("ASM Web Sites") and other sources. This Privacy Policy sets forth the information we collect about you, how we use this information and the choices you have about how we use such information.
FIND OUT MORE about the privacy policy