title: Fitness of Salmonella mutants resistant to antimicrobial peptides.
abstract: OBJECTIVE
  To examine the effects of mutations in the waaY, phoP and pmrB genes, which confer resistance to antimicrobial peptides (AMPs), on fitness of Salmonella Typhimurium.
  
  
  METHODS
  Survival during low pH, oxidative stress, stationary-phase incubation, exposure to serum and bile and growth in mice and laboratory media were determined by time-kills, disc inhibition assays, competition experiments and optical density measurements.
  
  
  RESULTS
  Individual mutations in the waaY gene (involved in LPS core biosynthesis) and in the phoP and pmrB genes (part of two different two-component regulatory systems, phoPQ and pmrAB) conferred no or minor effects on bacterial survival during stressful in vitro conditions or in mice. In contrast, a waaY-phoP-pmrB triple mutant was compromised under most assay conditions.
  
  
  CONCLUSIONS
  Results from this study show that AMP resistance can be cost-free, as assessed by several assays that attempt to mimic the conditions a bacterium might encounter within a host. Our findings imply that future therapeutic use of AMPs could select for fit mutants with cross-resistance to human defence peptides and that potential resistance development in response to therapeutic use of AMPs needs to be carefully monitored.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75123 Uppsala, Sweden.
authors.forename: Hava
authors.initials: H
authors.lastname: Lofton
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden Department of Biology, SBASSE Complex, Lahore University of Management Sciences, Lahore Cantt., 54792, Pakistan.
authors.forename: Naeem
authors.initials: N
authors.lastname: Anwar
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Rhen
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75123 Uppsala, Sweden dan.andersson@imbim.uu.se.
authors.forename: Dan I
authors.initials: DI
authors.lastname: Andersson
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001646:Bile; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D056084:Genetic Fitness; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects / Q000235:genetics; D009154:Mutation; D018384:Oxidative Stress; D012475:Salmonella / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides
keywords: Salmonella Typhimurium, resistance; bile; growth rate; mice; oxidative stress; pH response; serum