Fitness and molecular mechanisms of resistance to rifaximin in in vitro selected Escherichia coli mutants

Microb Drug Resist. 2012 Aug;18(4):376-9. doi: 10.1089/mdr.2011.0010. Epub 2011 Jun 28.

Abstract

Aims: This study sought to analyze the molecular mechanisms contributing to the development of rifaximin (Rfx) resistance in vitro in Escherichia coli. Twenty-eight Rfx-resistant mutants as well as four clinical isolates of E. coli were analyzed. The results obtained show that mutations in the rpoB gene and overexpression of Phe-Arg-β-naphthylamide (PAβN)-inhibitible efflux pump were implicated in Rfx resistance.

Results: Amino acid substitutions at position 516 of the β-subunit of RNA polymerases were the most frequently obtained (53.6% of the mutants). The efflux pump inhibitor decreased the minimal inhibitory concentration (MIC) of 71.43% (20/28) of the mutant strains.

Conclusions: Mutations studied in the rpoB gene and overexpression of PAβN-inhibitible efflux pumps contribute to Rfx resistance (together or not), whereas alterations in porin levels do not seem to have a relevant role in the acquisition of Rfx resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Outer Membrane Proteins / genetics
  • DNA-Directed RNA Polymerases
  • Dipeptides / pharmacology
  • Drug Resistance, Bacterial / drug effects*
  • Drug Resistance, Bacterial / physiology
  • Escherichia coli / drug effects
  • Escherichia coli / genetics*
  • Escherichia coli / isolation & purification
  • Escherichia coli Proteins / genetics*
  • Gene Expression Regulation, Bacterial
  • Humans
  • Microbial Sensitivity Tests
  • Point Mutation
  • Rifamycins / pharmacology*
  • Rifaximin

Substances

  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Dipeptides
  • Escherichia coli Proteins
  • Rifamycins
  • phenylalanylarginine-naphthylamide
  • rpoB protein, E coli
  • DNA-Directed RNA Polymerases
  • Rifaximin