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The AcrAB-TolC pump is involved in multidrug resistance in clinical Shigella flexneri isolates

Haiyan Yang1, Guangcai Duan, Jingyuan Zhu

  • 1Department of Epidemiology, College of Public Health of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

Microbial Drug Resistance (Larchmont, N.Y.)
|November 28, 2008
PubMed

Insights

Overexpression of the acrA gene contributes to multiple-antibiotic resistance (Mar) in Shigella flexneri. Efflux pump inhibitors showed potential in restoring ciprofloxacin susceptibility in resistant strains.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Shigella flexneri is a significant cause of bacterial dysentery.
  • Multiple-antibiotic resistance (Mar) in bacterial pathogens poses a global health threat.
  • The AcrAB-TolC efflux pump system is crucial for multidrug resistance in many Gram-negative bacteria.

Purpose of the Study:

  • To investigate the role of the AcrAB-TolC efflux pump in the multiple-antibiotic resistance (Mar) of Shigella flexneri clinical isolates.
  • To identify genetic mutations associated with Mar phenotypes in Shigella flexneri.
  • To evaluate the efficacy of efflux pump inhibition in overcoming antibiotic resistance.

Main Methods:

  • Characterization of Mar and susceptible Shigella flexneri isolates.
  • Quantitative PCR and Northern blot analysis to determine acrAB-tolC gene expression levels.
  • DNA sequencing of acrAB-tolC genes in selected isolates.
  • Ciprofloxacin accumulation assays and efflux inhibition studies using Phe-Arg-beta-naphthylamide.

Main Results:

  • Ciprofloxacin accumulation was significantly lower in Mar isolates compared to susceptible isolates.
  • The expression of acrA mRNA was significantly higher in Mar isolates.
  • Specific mutations in acrA and tolC genes were identified in resistant and susceptible strains, respectively.
  • Efflux pump inhibitors demonstrated efficacy in restoring ciprofloxacin susceptibility in some Mar isolates.

Conclusions:

  • Overexpression of the acrA gene is a key mechanism driving Mar in clinical Shigella flexneri isolates.
  • Acquired resistance to ciprofloxacin can be reversed using efflux pump inhibitors like Phe-Arg-beta-naphthylamide.
  • The AcrAB-TolC efflux pump system represents a potential therapeutic target for combating antibiotic resistance in Shigella flexneri.

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