title: Detection and prevalence of active drug efflux mechanism in various multidrug-resistant Klebsiella pneumoniae strains from Turkey.
abstract: The prevalence of active drug efflux pump and porin alterations was investigated in Turkish nosocomial strains of Klebsiella pneumoniae exhibiting a multidrug-resistant phenotype. MICs of various antibiotics, including quinolones, chloramphenicol, tetracycline, and beta-lactams, for those strains were determined either with or without the efflux pump inhibitor phenylalanine arginine beta-naphthylamide (PAbetaN). Thirty-nine percent of the strains exhibited a PAbetaN-modulated resistance for quinolones, chloramphenicol, and tetracycline. In these strains, a significant increase of chloramphenicol accumulation was gained in the presence of the efflux pump inhibitor PAbetaN or with the energy uncoupler carbonyl cyanide m-chlorophenylhydrazone. Moreover, high-level expression of the membrane fusion protein AcrA, which was immunodetected in most of those isolates, suggests that the AcrAB/TolC efflux machinery contributed to their antibiotic resistance. Studies of K. pneumoniae porins indicated that the majority of the strains, including extended-spectrum beta-lactamase producers and efflux-positive ones, presented an alteration in their sorbitol-sensitive porin (OmpK35) expression. This is the first report showing the prominent role of active drug efflux in the antibiotic resistance of nosocomial K. pneumoniae strains from Turkey.
authors.affiliation: Department of Microbiology, School of Medicine, Marmara University, Istanbul, Turkey.
authors.forename: Ufuk Over
authors.initials: UO
authors.lastname: Hasdemir
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chevalier
authors.forename: Patrice
authors.initials: P
authors.lastname: Nordmann
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pagès
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D001426:Bacterial Proteins / Q000032:analysis; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002701:Chloramphenicol / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial; D029968:Escherichia coli Proteins / Q000032:analysis; D006867:Hydrolases / Q000032:analysis; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000032:analysis
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C119261:OmpK35 porin, Klebsiella pneumoniae; D018272:Porins; C482905:OmpX protein, E coli; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D002701:Chloramphenicol; D006867:Hydrolases