A Protein Important for Antimicrobial Peptide Resistance, YdeI/OmdA, Is in the Periplasm and Interacts with OmpD/NmpC

Pilonieta, M. Carolina; Erickson, Kimberly D.; Ernst, Robert K.; Detweiler, Corrella S.

doi:10.1128/jb.00688-09

Cited by 50 publications

(48 citation statements)

References 73 publications

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“…This porin lack was associated with a decrease in the virulence index of K. pneumoniae strains, as reflected by the significant modification of the kinetics of the killing of the nematodes even in strains that overexpressed an efflux pump. Involvement of porins in bacterial virulence has been mentioned by some teams (12,29,31,35). However, this is the first time that a correlation between porin expression and level of virulence has been demonstrated for K. pneumoniae.…”

Section: Discussionmentioning

confidence: 91%

Membrane Efflux and Influx Modulate both Multidrug Resistance and Virulence of Klebsiella pneumoniae in a Caenorhabditis elegans Model

Bialek

Lavigne

Chevalier

et al. 2010

Antimicrob Agents Chemother

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Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones (nalidixic acid [NAL]) related to a putative efflux system overexpression has recently been reported for Klebsiella pneumoniae. The potential impact of this multidrug resistance (MDR) on the virulence of K. pneumoniae was evaluated in the Caenorhabditis elegans model. For 2 of the 3 MDR clinical isolates studied, a significant increase in acrB transcription was found in comparison with their antibiotic-susceptible revertants. ATCC 138821 and MDR, revertant, and derivative strains with altered porin expression were studied. Strains proved or suspected to overexpress an efflux system were significantly more virulent than the ATCC and revertant strains (time to kill 50% of nematodes [LT 50 ] in days: 3.4 to 3.8 ؎ 0.2 versus 4.1 to 4.4 ؎ 0.3, P < 0.001). Inversely, strains with altered porin expression were significantly less virulent, independently of the expression level of efflux system (LT 50 ‫؍‬ 5.4 to 5.6 ؎ 0.2, P < 0.001). Altered porin expression did not change MICs of CMP and NAL but did those of FOX (4 to 16؋ MIC) and ertapenem (16 to 64؋ MIC). The strains with a normally or an overexpressed efflux system that received the ␤-lactamase CTX-M-15 became more widely resistant without modification of their virulence potential, suggesting that balance between resistance and virulence is dependent on the type of resistance mechanisms. In conclusion, this study shows that the expression of both efflux systems and porins is a key factor not only for antibiotic resistance but also virulence potential in K. pneumoniae.Klebsiella pneumoniae, which was recognized over 100 years ago as a cause of community-acquired pneumonia and 20 years ago as a cause of community-acquired pyogenic liver abscesses, is also a common cause of nosocomial infections that range from mild urinary tract infections to severe respiratory tract infections and bacteremia (15,30). Moreover, K. pneumoniae has been found to produce various plasmid-mediated enzymes which confer resistance to most ␤-lactams, particularly the extended-spectrum cephalosporins and more recently carbapenems (2,22,24). Treatment of serious infections caused by extended-spectrum ␤-lactamase (ESBL)-producing K. pneumoniae bacteria is difficult because these organisms are frequently resistant to various other families of antibiotics, including fluoroquinolones (28). Fluoroquinolone resistance in K. pneumoniae arises through specific mutations within the target proteins DNA gyrase and topoisomerase IV and also through a lower uptake of quinolones because of efflux system overexpression (3, 18). Ruzin et al. showed that the resistance to quinolones related to overexpression of the AcrAB efflux pump of K. pneumoniae was associated to resistance to other antibiotics, including chloramphenicol, erythromycin, tetracycline, and also tigecycline, a recently commercialized molecule (32). As for us, we showed that cross-resistance to cefoxitin, chloramphenicol, and quinolones that we observed in bacteremia K. pn...

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Section: Discussionmentioning

confidence: 91%

Membrane Efflux and Influx Modulate both Multidrug Resistance and Virulence of Klebsiella pneumoniae in a Caenorhabditis elegans Model

Bialek

Lavigne

Chevalier

et al. 2010

Antimicrob Agents Chemother

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“…Proteins with such domains can serve a variety of functions and have been implicated in bacterial pathogenesis (36). In fact, the Fe(III)-binding PmrA/PmrB regulates a similar periplasmic OB-fold protein (OmdA) that confers resistance to polymyxin B, a cationic antimicrobial peptide (42). Whether PA14_04180 confers a similar resistance in Pseudomonas species is currently unknown.…”

Section: Discussionmentioning

confidence: 99%

BqsR/BqsS Constitute a Two-Component System That Senses Extracellular Fe(II) in Pseudomonas aeruginosa

Kreamer¹,

Wilks²,

Marlow³

et al. 2011

Journal of Bacteriology

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Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium best known as the predominant opportunistic pathogen infecting the lungs of cystic fibrosis patients. In this context, it is thought to form biofilms, within which locally reducing and acidic conditions can develop that favor the stability of ferrous iron [Fe(II)]. Because iron is a signal that stimulates biofilm formation, we performed a microarray study to determine whether P. aeruginosa strain PA14 exhibits a specific transcriptional response to extracellular Fe(II). Among the genes that were most upregulated in response to Fe(II) were those encoding the twocomponent system BqsR/BqsS, previously identified for its role in P. aeruginosa strain PAO1 biofilm decay (13)

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“…This suggests that YgiW is the main effector of the FirRS system in NTHI. BOF proteins like YgiW are not well characterized; however, they have been implicated in stress responses (51,70). CusF, another BOF protein, has been shown to bind to copper (29,53), so perhaps YgiW plays a role in the resistance to high levels of Fe 2ϩ or Zn 2ϩ .…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Ferrous Iron-Responsive Two-Component System in Nontypeable Haemophilus influenzae

et al. 2012

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Nontypeable Haemophilus influenzae (NTHI), an opportunistic pathogen that is commonly found in the human upper respiratory tract, has only four identified two-component signal transduction systems. One of these, an ortholog to the QseBC (quorum-sensing Escherichia coli) system, was characterized. This system, designated firRS, was found to be transcribed in an operon with a gene encoding a small, predicted periplasmic protein with an unknown function, ygiW. The ygiW-firRS operon exhibited a unique feature with an attenuator present between ygiW and firR that caused the ygiW transcript level to be 6-fold higher than the ygiW-firRS transcript level. FirRS induced expression of ygiW and firR, demonstrating that FirR is an autoactivator. Unlike the QseBC system of E. coli, FirRS does not respond to epinephrine or norepinephrine. FirRS signal transduction was stimulated when NTHI cultures were exposed to ferrous iron or zinc but was unresponsive to ferric iron. Notably, the ferrous iron-responsive activation only occurred when a putative iron-binding site in FirS and the key phosphorylation aspartate in FirR were intact. FirRS was also activated when cultures were exposed to cold shock. Mutants in ygiW, firR, and firS were attenuated during pulmonary infection, but not otitis media. These data demonstrate that the H. influenzae strain 2019 FirRS is a two-component regulatory system that senses ferrous iron and autoregulates its own operon.

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A Protein Important for Antimicrobial Peptide Resistance, YdeI/OmdA, Is in the Periplasm and Interacts with OmpD/NmpC

Cited by 50 publications

References 73 publications

Membrane Efflux and Influx Modulate both Multidrug Resistance and Virulence of Klebsiella pneumoniae in a Caenorhabditis elegans Model

Membrane Efflux and Influx Modulate both Multidrug Resistance and Virulence of Klebsiella pneumoniae in a Caenorhabditis elegans Model

BqsR/BqsS Constitute a Two-Component System That Senses Extracellular Fe(II) in Pseudomonas aeruginosa

Characterization of a Ferrous Iron-Responsive Two-Component System in Nontypeable Haemophilus influenzae

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