Role of the MexEF-OprN efflux system in low-level resistance of Pseudomonas aeruginosa to ciprofloxacin

Article Article scientifique Article Role of the MexEF-OprN efflux system in low-level resistance of Pseudomonas aeruginosa to ciprofloxacin eng 2011 author Llanes Catherine author Kohler Thilo 0000-0003-4889-9492 23327 author Patry Isabelle 85694 author Dehecq Barbara author Van Delden Christian 24088 author Plésiat Patrick 5676-5684 10.1128/AAC.00101-11 21911574 0066-4804 In this study, we investigated the resistance mechanisms to fluoroquinolones of 85 non-cystic fibrosis strains of Pseudomonas aeruginosa exhibiting a reduced susceptibility to ciprofloxacin (MICs from 0.25 to 2 μg/ml). In addition to MexAB-OprM (31 of 85 isolates) and MexXY/OprM (39 of 85), the MexEF-OprN efflux pump (10 of 85) was found to be commonly upregulated in this population that is considered susceptible or of intermediate susceptibility to ciprofloxacin, according to current breakpoints. Analysis of the 10 MexEF-OprN overproducers (nfxC mutants) revealed the presence of various mutations in the mexT (2 isolates), mexS (5 isolates), and/or mvaT (2 isolates) genes, the inactivation of which is known to increase the expression of the mexEF-oprN operon in reference strain PAO1-UW. However, these genes were intact in 3 of 10 of the clinical strains. Interestingly, ciprofloxacin at 2 μg/ml or 4 μg/ml preferentially selected nfxC mutants from wild-type clinical strains (n = 10 isolates) and from first-step mutants (n = 10) overexpressing Mex pumps, thus indicating that MexEF-OprN represents a major mechanism by which P. aeruginosa may acquire higher resistance levels to fluoroquinolones. These data support the notion that the nfxC mutants may be more prevalent in the clinical setting than anticipated and strongly suggest the involvement of still unknown genes in the regulation of this efflux system. Anti-Bacterial Agents/pharmacology Bacterial Outer Membrane Proteins/genetics/metabolism Ciprofloxacin/pharmacology Drug Resistance, Bacterial/genetics Fluoroquinolones/pharmacology Gene Expression Regulation, Bacterial Humans Membrane Transport Proteins/genetics/metabolism Microbial Sensitivity Tests Mutation Operon Polymerase Chain Reaction Pseudomonas Infections/microbiology Pseudomonas aeruginosa/drug effects/genetics/metabolism Sequence Analysis, DNA Dewey 616 54 Département de microbiologie et médecine moléculaire 21B 56 Département de médecine 221 false 235 Perception du Quorum et gènes de virulence 301 Antimicrobial agents and chemotherapy 55 12 227b9a12-5e5a-4fdd-853e-aa6ab782743c Article (Published version) Restricted 2011_Llanes_RoleMexEFOprn_AntimicroAgeChemoth.pdf 97201 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté de médecine / Section de médecine clinique / Département de médecine

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Role of the MexEF-OprN efflux system in low-level resistance of Pseudomonas aeruginosa to ciprofloxacin	Antimicrobial agents and chemotherapy			2011	772	0

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Patry, Isabelle