title: Parallel evolutionary pathways to antibiotic resistance selected by biocide exposure.
abstract: OBJECTIVE
  Biocides are widely used to prevent infection. We aimed to determine whether exposure of Salmonella to various biocides could act as a driver of antibiotic resistance.
  
  
  METHODS
  Salmonella enterica serovar Typhimurium was exposed to four biocides with differing modes of action. Antibiotic-resistant mutants were selected during exposure to all biocides and characterized phenotypically and genotypically to identify mechanisms of resistance.
  
  
  RESULTS
  All biocides tested selected MDR mutants with decreased antibiotic susceptibility; these occurred randomly throughout the experiments. Mutations that resulted in de-repression of the multidrug efflux pump AcrAB-TolC were seen in MDR mutants. A novel mutation in rpoA was also selected and contributed to the MDR phenotype. Other mutants were highly resistant to both quinolone antibiotics and the biocide triclosan.
  
  
  CONCLUSIONS
  This study shows that exposure of bacteria to biocides can select for antibiotic-resistant mutants and this is mediated by clinically relevant mechanisms of resistance prevalent in human pathogens.
authors.affiliation: Antimicrobials Research Group, School of Immunity and Infection and Institute for Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK m.a.webber@bham.ac.uk.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Webber
authors.affiliation: Antimicrobials Research Group, School of Immunity and Infection and Institute for Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Rebekah N
authors.initials: RN
authors.lastname: Whitehead
authors.affiliation: Antimicrobials Research Group, School of Immunity and Infection and Institute for Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Manuella
authors.initials: M
authors.lastname: Mount
authors.affiliation: School of Bioscience and Institute for Microbiology & Infection, College of Life and Environmental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Loman
authors.affiliation: Division of Microbiology and Infection, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pallen
authors.affiliation: Antimicrobials Research Group, School of Immunity and Infection and Institute for Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Laura J V
authors.initials: LJ
authors.lastname: Piddock
mesh_terms: D004202:Disinfectants / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D019143:Evolution, Molecular; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010641:Phenotype; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D004202:Disinfectants
keywords: MDR; disinfectant; efflux