Role of the MexEF-OprN Efflux System in Low-Level Resistance of Pseudomonas aeruginosa to Ciprofloxacin

Autor: Patrick Plésiat, Thilo Köhler, Catherine Llanes, Christian van Delden, Isabelle Patry, Barbara Dehecq
Přispěvatelé: Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Service de bactériologie [Besançon], Centre National de Référence de la Résistance aux Antibiotiques ( CNR ), Transplantation Infection Disease Unity, Hôpitaux Universitaires de Genève ( HUG ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre National de Référence de la Résistance aux Antibiotiques (CNR), Hôpitaux Universitaires de Genève (HUG)
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Fluoroquinolones/pharmacology
Operon
Mutant
Population
Microbial Sensitivity Tests
Drug resistance
Biology
[ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
medicine.disease_cause
Polymerase Chain Reaction
Bacterial Outer Membrane Proteins/genetics/metabolism
Ciprofloxacin/pharmacology
Anti-Bacterial Agents/pharmacology
Microbiology
Bacterial genetics
03 medical and health sciences
Mechanisms of Resistance
Ciprofloxacin
Drug Resistance
Bacterial
medicine
Humans
Pseudomonas Infections
Pharmacology (medical)
Membrane Transport Proteins/genetics/metabolism
education
Pseudomonas Infections/microbiology
030304 developmental biology
ddc:616
Pharmacology
0303 health sciences
education.field_of_study
030306 microbiology
Pseudomonas aeruginosa
Membrane Transport Proteins
Drug Resistance
Bacterial/genetics
Gene Expression Regulation
Bacterial
Sequence Analysis
DNA
Pseudomonas aeruginosa/drug effects/genetics/metabolism
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Anti-Bacterial Agents
Infectious Diseases
Mutation
Efflux
Bacterial Outer Membrane Proteins
Fluoroquinolones
medicine.drug
Zdroj: Antimicrobial Agents and Chemotherapy
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2011, 55 (12), pp.5676-5684. 〈10.1128/AAC.00101-11〉
Antimicrobial Agents and Chemotherapy, Vol. 55, No 12 (2011) pp. 5676-84
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2011, 55 (12), pp.5676-5684. ⟨10.1128/AAC.00101-11⟩
ISSN: 0066-4804
1098-6596
DOI: 10.1128/AAC.00101-11〉
Popis: 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.
Databáze: OpenAIRE
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