Role of an acrR mutation in multidrug resistance of in vitro-selected fluoroquinolone-resistant mutants of Salmonella enterica serovar Typhimurium

FEMS Microbiol Lett. 2004 Sep 1;238(1):267-72. doi: 10.1016/j.femsle.2004.07.046.

Abstract

Quinolone resistance in Salmonella spp. is usually attributed to both active efflux and mutations leading to modification of the target enzymes DNA gyrase and topoisomerase IV. Here, we investigated the presence of mutations in the efflux regulatory genes of fluoroquinolone- and multidrug-resistant mutants of Salmonella enterica serovar Typhimurium (S. Typhimurium) selected in vitro with enrofloxacin that both carried a mutation in the target gene gyrA and overproduced the AcrAB efflux pump. No mutations were detected in the global regulatory loci marRAB and soxRS for the four strains studied. A mutation in acrR, the local repressor of acrAB, was found for two ciprofloxacin-resistant selected-mutants, leading to duplication of amino acids Ile75 and Glu76. Complementation experiments with wild-type acrR showed that the mutation identified in acrR partially contributed to the increase in resistance levels to several unrelated antibiotics. The acrR mutation also contributed to acrAB overexpression as shown by RT-PCR. Thus, this study underlines the role of an acrR mutation, in addition to the mutation in gyrA, in the fluoroquinolone and multidrug resistance phenotype of S. Typhimurium mutants, through overexpression of acrAB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Biological Transport, Active
  • DNA Gyrase / genetics
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Enrofloxacin
  • Fluoroquinolones / pharmacology*
  • Genetic Complementation Test
  • Membrane Transport Proteins / genetics*
  • Mutation*
  • Quinolones / pharmacology
  • RNA, Bacterial / analysis
  • RNA, Messenger / analysis
  • Repressor Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salmonella typhimurium / drug effects*
  • Salmonella typhimurium / genetics
  • Trans-Activators / genetics
  • Transcription Factors / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Fluoroquinolones
  • MarA protein, Salmonella enterica
  • Membrane Transport Proteins
  • Quinolones
  • RNA, Bacterial
  • RNA, Messenger
  • Repressor Proteins
  • SoxS protein, Salmonella enterica
  • Trans-Activators
  • Transcription Factors
  • multiple antibiotic resistance protein B
  • SoxR protein, Bacteria
  • Enrofloxacin
  • DNA Gyrase