Contribution of the AcrAB-TolC Efflux Pump to High-Level Fluoroquinolone Resistance in <i>Escherichia coli</i> Isolated from Dogs and Humans

  • SATO Toyotaka
    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 069–8501, Japan
  • YOKOTA Shin-ichi
    Department of Microbiology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo 060–8556, Hokkaido, Japan
  • OKUBO Torahiko
    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 069–8501, Japan
  • ISHIHARA Kanako
    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 069–8501, Japan
  • UENO Hiroshi
    Laboratory of Zoonoses, Department of Health and Environmental Sciences, School of Veterinary Medicine, Rakuno Gakuen University, 582 Midorimachi, Bunkyoudai, Ebetsu, Hokkaido 069–8501, Japan
  • MURAMATSU Yasukazu
    Laboratory of Zoonoses, Department of Health and Environmental Sciences, School of Veterinary Medicine, Rakuno Gakuen University, 582 Midorimachi, Bunkyoudai, Ebetsu, Hokkaido 069–8501, Japan
  • FUJII Nobuhiro
    Department of Microbiology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo 060–8556, Hokkaido, Japan
  • TAMURA Yutaka
    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 069–8501, Japan

抄録

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.

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