title: Exposure of Salmonella enterica serovar Typhimurium to high level biocide challenge can select multidrug resistant mutants in a single step.
abstract: BACKGROUND
  Biocides are crucial to the prevention of infection by bacteria, particularly with the global emergence of multiply antibiotic resistant strains of many species. Concern has been raised regarding the potential for biocide exposure to select for antibiotic resistance due to common mechanisms of resistance, notably efflux.
  
  
  RESULTS
  Salmonella enterica serovar Typhimurium was challenged with 4 biocides of differing modes of action at both low and recommended-use concentration. Flow cytometry was used to investigate the physiological state of the cells after biocide challenge. After 5 hours exposure to biocide, live cells were sorted by FACS and recovered. Cells recovered after an exposure to low concentrations of biocide had antibiotic resistance profiles similar to wild-type cells. Live cells were recovered after exposure to two of the biocides at in-use concentration for 5 hours. These cells were multi-drug resistant and accumulation assays demonstrated an efflux phenotype of these mutants. Gene expression analysis showed that the AcrEF multidrug efflux pump was de-repressed in mutants isolated from high-levels of biocide.
  
  
  CONCLUSIONS
  These data show that a single exposure to the working concentration of certain biocides can select for mutant Salmonella with efflux mediated multidrug resistance and that flow cytometry is a sensitive tool for identifying biocide tolerant mutants. The propensity for biocides to select for MDR mutants varies and this should be a consideration when designing new biocidal formulations.
authors.affiliation: Antimicrobial Agents Research Group, School of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom. r.n.whitehead@bham.ac.uk
authors.forename: Rebekah N
authors.initials: RN
authors.lastname: Whitehead
authors.forename: Tim W
authors.initials: TW
authors.lastname: Overton
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Kemp
authors.forename: Mark A
authors.initials: MA
authors.lastname: Webber
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004202:Disinfectants / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*; D012480:Salmonella Infections / Q000188:drug therapy / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004202:Disinfectants