title: Contribution of the AcrAB-TolC efflux pump to high-level fluoroquinolone resistance in Escherichia coli isolated from dogs and humans.
abstract: Fluoroquinolone resistance is mainly caused by mutations in quinolone resistance-determining regions of DNA gyrase and topoisomerase IV in Escherichia coli. The AcrAB-TolC efflux pump contributes to resistance against fluoroquinolone and other antimicrobials. In this study, we investigated a high-level mechanism of fluoroquinolone resistance in E. coli that was isolated from human clinical samples and canine fecal samples. E. coli strains with high levels of fluoroquinolone resistance have been found to be frequently resistant to cephalosporins. Strains with high-level fluoroquinolone resistance exhibited lower intracellular enrofloxacin (ENR) concentrations, higher expression of AcrA, and a greater reduction in the fluoroquinolone minimum inhibitory concentration for treatment with an efflux pump inhibitor. The frequency of strains with enhanced ENR resistance selection and the survival rate of E. coli in the presence of ENR in vitro were correlated well with AcrA protein expression levels in the parental strains. These results suggest that AcrAB-TolC efflux pump over-expression is related to high-level fluoroquinolone resistance and the selection of strains with enhanced fluoroquinolone resistance.
authors.affiliation: Laboratory of Food Microbiology and Food Safety, Department of Health and Environmental Sciences, School of Veterinary Medicine, Rakuno Gakuen University, 582 Midorimachi, Bunkyoudai, Ebetsu, Hokkaido, Japan.
authors.forename: Toyotaka
authors.initials: T
authors.lastname: Sato
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yokota
authors.forename: Torahiko
authors.initials: T
authors.lastname: Okubo
authors.forename: Kanako
authors.initials: K
authors.lastname: Ishihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueno
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Muramatsu
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Fujii
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tamura
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004283:Dog Diseases / Q000188:drug therapy / Q000382:microbiology*; D004285:Dogs; D024881:Drug Resistance, Bacterial / Q000235:genetics; D000077422:Enrofloxacin; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D016133:Polymerase Chain Reaction / Q000662:veterinary
chemical_list: C083497:AcrA protein, E coli; D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones; D008074:Lipoproteins; D026901:Membrane Transport Proteins; D000077422:Enrofloxacin