title: Fitness and molecular mechanisms of resistance to rifaximin in in vitro selected Escherichia coli mutants.
abstract: OBJECTIVE
  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.
authors.affiliation: Centre de Recerca en Salut Internacional de Barcelona, IDIBAPS-Hospital Clinic-Universitat de Barcelona, Rosselló, Barcelona, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Pons
authors.forename: Laura
authors.initials: L
authors.lastname: Mensa
authors.forename: Joaquim
authors.initials: J
authors.lastname: Gascón
authors.forename: Joaquim
authors.initials: J
authors.lastname: Ruiz
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D012321:DNA-Directed RNA Polymerases; D004151:Dipeptides / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000502:physiology; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D029968:Escherichia coli Proteins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D017354:Point Mutation; D012294:Rifamycins / Q000494:pharmacology*; D000078262:Rifaximin
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D004151:Dipeptides; D029968:Escherichia coli Proteins; D012294:Rifamycins; C474925:phenylalanylarginine-naphthylamide; C540081:rpoB protein, E coli; D012321:DNA-Directed RNA Polymerases; D000078262:Rifaximin