title: mig-14 is a Salmonella gene that plays a role in bacterial resistance to antimicrobial peptides.
abstract: It was previously demonstrated that the mig-14 gene of Salmonella enterica serovar Typhimurium is necessary for bacterial proliferation in the liver and spleen of mice following intragastric inoculation and that mig-14 expression, which is induced within macrophages, is under the control of the global regulator PhoP. Here we demonstrate that the mig-14 promoter is induced by growth in minimal medium containing low magnesium or acidic pH, consistent with regulation by PhoP. In addition, mig-14 is strongly induced by polymyxin B, protamine, and the mammalian antimicrobial peptide protegrin-1. While phoP is necessary for the induction of mig-14 in response to protamine and protegrin, mig-14 is still induced by polymyxin B in a phoP background. We also demonstrate that mig-14 is necessary for resistance of S. enterica serovar Typhimurium to both polymyxin B and protegrin-1. Gram-negative resistance to a variety of antimicrobial peptides has been correlated with modifications of lipopolysaccharide structure. However, we show that mig-14 is not required for one of these modifications, the addition of 4-aminoarabinose to lipid A. Additionally, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of wild-type and mig-14 lipopolysaccharide also shows no detectable differences between the two strains. Therefore, mig-14 contributes to Salmonella resistance to antimicrobial peptides by a mechanism that is not yet fully understood.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA. ibrodsky@leland.stanford.edu
authors.forename: Igor E
authors.initials: IE
authors.lastname: Brodsky
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ernst
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
authors.forename: Stanley
authors.initials: S
authors.lastname: Falkow
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D003470:Culture Media; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D008274:Magnesium / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D012475:Salmonella / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D003470:Culture Media; D011479:Protamines; D011506:Proteins; C094880:protegrin-1; C061064:PhoP protein, Bacteria; D008274:Magnesium; D011112:Polymyxin B