Recognition of mechanisms involved in bile resistance important to halting antimicrobial resistance in nontyphoidal Salmonella

Ming Han Tsai, Sih Ru Wu, Hao Yuan Lee, Chyi Liang Chen, Tzou Yien Lin, Yhu Chering Huang, Cheng Hsun Chiu

研究成果: 雜誌貢獻文章同行評審

10 引文 斯高帕斯(Scopus)


Increasing antimicrobial resistance in nontyphoidal Salmonella (NTS) is a global public health problem that complicates antimicrobial therapy. As an enteric pathogen, Salmonella must endure the presence of bile in the intestinal tract during the course of infection. In this study, we sought to identify Salmonella genes necessary for bile resistance and to investigate their association with antimicrobial resistance. Four genes related to bile resistance were identified, namely rfaP, rfbK, dam and tolC. The first three genes are involved in lipopolysaccharide synthesis, and tolC is associated with an efflux pump. Antimicrobial susceptibility testing showed increased susceptibility to polymyxin B and ciprofloxacin in rfaP and tolC mutants of Salmonella, respectively. Genetic analysis of 45 clinical isolates of NTS revealed that all isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration ≥0.125 mg/L) were associated with point mutations in the quinolone resistance-determining regions of the gyrA and parC genes. The efflux pump also played a role, as evidenced by the reduction in fluoroquinolone resistance when the TolC efflux pump was inhibited by Phe-Arg-β- naphthylamide, a competitive efflux pump inhibitor. Based on these results, we conclude that an intact membrane structure and the efflux pump system provide mechanisms enabling NTS to resist bile. Caution should be taken when using ciprofloxacin and polymyxin B to treat Salmonella enteric infection, as resistance to these agents involves the same mechanisms. Addition of an efflux pump inhibitor to fluoroquinolones may be an effective strategy to deal with the increasing resistance in NTS.
頁(從 - 到)151-157
期刊International Journal of Antimicrobial Agents
出版狀態已發佈 - 8月 2012

ASJC Scopus subject areas

  • 微生物學(醫學)
  • 傳染性疾病
  • 藥學(醫學)


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