Genomewide Identification of Genetic Determinants of Antimicrobial Drug Resistance in<i>Pseudomonas aeruginosa</i>

Dötsch, Andreas; Becker, Tanja; Pommerenke, Claudia; Magnowska, Zofia; Jänsch, Lothar; Häußler, Susanne

doi:10.1128/aac.00035-09

Cited by 120 publications

(124 citation statements)

References 52 publications

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“…A single-amino-acid change in parE was found compared to the genome of PAO1, but this mutation has not been associated with resistance. It has been reported that mutations in the PAO1 genes PA1259 and PA2110 can lead to increased resistance to ciprofloxacin (12). The equivalents of these genes in the genome of isolate 39016 either are incomplete or are pseudogenes, which may explain the resistance phenotype.…”

Section: Distribution Of Clones Among the Keratitis Isolatesmentioning

confidence: 99%

Genetic Characterization Indicates that a Specific Subpopulation of Pseudomonas aeruginosa Is Associated with Keratitis Infections

et al. 2011

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Pseudomonas aeruginosa is a common opportunistic bacterial pathogen that causes a variety of infections in humans. Populations of P. aeruginosa are dominated by common clones that can be isolated from diverse clinical and environmental sources. To determine whether specific clones are associated with corneal infection, we used a portable genotyping microarray system to analyze a set of 63 P. aeruginosa isolates from patients with corneal ulcers (keratitis). We then used population analysis to compare the keratitis isolates to a wider collection of P. aeruginosa from various nonocular sources. We identified various markers in a subpopulation of P. aeruginosa associated with keratitis that were in strong disequilibrium with the wider P. aeruginosa population, including oriC, exoU, katN, unmodified flagellin, and the carriage of common genomic islands. The genome sequencing of a keratitis isolate (39016; representing the dominant serotype O11), which was associated with a prolonged clinical healing time, revealed several genomic islands and prophages within the accessory genome. The PCR amplification screening of all 63 keratitis isolates, however, provided little evidence for the shared carriage of specific prophages or genomic islands between serotypes. P. aeruginosa twitching motility, due to type IV pili, is implicated in corneal virulence. We demonstrated that 46% of the O11 keratitis isolates, including 39016, carry a distinctive pilA, encoding the pilin of type IV pili. Thus, the keratitis isolates were associated with specific characteristics, indicating that a subpopulation of P. aeruginosa is adapted to cause corneal infection.Pseudomonas aeruginosa is a common infective cause of corneal ulceration (bacterial keratitis) (14,32,54). P. aeruginosa keratitis is frequently associated with contact lens wear (54), because hypoxia and trauma from the contact lens allows bacterial adhesion, and as the bacterium is a common contaminant of moist areas such as a contact lens case, the exposure of the ocular surface to the bacterium can easily occur. Subsequently, a combination of P. aeruginosa virulence factors and damage to host ocular defenses allows infection to develop. The host immune and inflammatory responses then contribute both to the elimination of the bacteria and to associated damage to tissues (14). P. aeruginosa is an opportunistic pathogen that is capable of causing a range of infections (16, 38), and it carries an impressive array of virulence factors. The virulence factors implicated in keratitis include twitching motility associated with type IV pili (63), flagella (13), a type III secretion system (22), and quorum-sensing regulated exoproducts (58).The genome of P. aeruginosa consists of core genes (approximately 90%) and accessory genes (approximately 10%) (40).The core genome, carried by all strains of P. aeruginosa, includes many of the recognized virulence genes (61). However, some strain-variable virulence-associated genes also occur, often clustered within genomic islands (3,33,47,50,60,61)....

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Section: Distribution Of Clones Among the Keratitis Isolatesmentioning

confidence: 99%

Genetic Characterization Indicates that a Specific Subpopulation of Pseudomonas aeruginosa Is Associated with Keratitis Infections

et al. 2011

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“…In favor of this hypothesis are the numerous reports indicating a modification of the oprF mutant against various classes of antibiotics. In P. aeruginosa PA14, loss of OprF induces susceptibility to a very broad spectrum of antimicrobials, such as carbapenem (ertapenem), cephalosporins (cefotaxime), aminoglycosides (levofloxacin), tetracyclines (tigecycline) (25), and also the fluoroquinolone ciprofloxacin (10). In their study, Woodruff and Hancock (68) showed that oprF mutant strain H636 was slightly more resistant to several ␤-lactam antibiotics, suggesting that the loss of OprF resulted in a modification of the OM structure, thus enhancing antibiotic uptake via nonporin pathways and counteracting the effects of the loss of OprF.…”

Section: Vol 79 2011mentioning

confidence: 99%

Full Virulence of Pseudomonas aeruginosa Requires OprF

et al. 2011

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OprF is a general outer membrane porin of Pseudomonas aeruginosa, a well-known human opportunistic pathogen associated with severe hospital-acquired sepsis and chronic lung infections of cystic fibrosis patients. A multiphenotypic approach, based on the comparative study of a wild-type strain of P. aeruginosa, its isogenic oprF mutant, and an oprF-complemented strain, showed that OprF is required for P. aeruginosa virulence. The absence of OprF results in impaired adhesion to animal cells, secretion of ExoT and ExoS toxins through the type III secretion system (T3SS), and production of the quorum-sensing-dependent virulence factors pyocyanin, elastase, lectin PA-1L, and exotoxin A. Accordingly, in the oprF mutant, production of the signal molecules N-(3-oxododecanoyl)-L-homoserine lactone and N-butanoyl-L-homoserine lactone was found to be reduced and delayed, respectively. Pseudomonas quinolone signal (PQS) production was decreased, while its precursor, 4-hydroxy-2-heptylquinoline (HHQ), accumulated in the cells. Taken together, these results show the involvement of OprF in P. aeruginosa virulence, at least partly through modulation of the quorum-sensing network. This is the first study showing a link between OprF, PQS synthesis, T3SS, and virulence factor production, providing novel insights into virulence expression.

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“…Recently, a number of resistomic studies have been carried out in P. aeruginosa (12)(13)(14)(15)(16)(17)(18). Genes of different functional classes have been identified to associate with intrinsic resistance against different types of antibiotics.…”

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confidence: 99%

A PhoPQ-Regulated ABC Transporter System Exports Tetracycline in Pseudomonas aeruginosa

Chen

Duan

2016

Antimicrob Agents Chemother

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bPseudomonas aeruginosa is an important human pathogen whose infections are difficult to treat due to its high intrinsic resistance to many antibiotics. Here, we show that the disruption of PA4456, encoding the ATP binding component of a putative ATP-binding cassette (ABC) transporter, increased the bacterium's susceptible to tetracycline and other antibiotics or toxic chemicals. Fluorescence spectroscopy and antibiotic accumulation tests showed that the interruption of the ABC transporter caused increased intracellular accumulation of tetracycline, demonstrating a role of the ABC transporter in tetracycline expulsion. Site-directed mutagenesis proved that the conserved residues of E170 in the Walker B motif and H203 in the H-loop, which are important for ATP hydrolysis, were essential for the function of PA4456. Through a genome-wide search, the PhoPQ twocomponent system was identified as a regulator of the computationally predicted PA4456-4452 operon that encodes the ABC transporter system. A >5-fold increase of the expression of this operon was observed in the phoQ mutant. The results obtained also show that the expression of the phzA1B1C1D1E1 operon and the production of pyocyanin were significantly higher in the ABC transporter mutant, signifying a connection between the ABC transporter and pyocyanin production. These results indicated that the PhoPQ-regulated ABC transporter is associated with intrinsic resistance to antibiotics and other adverse compounds in P. aeruginosa, probably by extruding them out of the cell.

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Genomewide Identification of Genetic Determinants of Antimicrobial Drug Resistance inPseudomonas aeruginosa

Cited by 120 publications

References 52 publications

Genetic Characterization Indicates that a Specific Subpopulation of Pseudomonas aeruginosa Is Associated with Keratitis Infections

Genetic Characterization Indicates that a Specific Subpopulation of Pseudomonas aeruginosa Is Associated with Keratitis Infections

Full Virulence of Pseudomonas aeruginosa Requires OprF

A PhoPQ-Regulated ABC Transporter System Exports Tetracycline in Pseudomonas aeruginosa

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