title: Mannitol utilisation is required for protection of Staphylococcus aureus from human skin antimicrobial fatty acids.
abstract: Mannitol (Mtl) fermentation, with the subsequent production of acid, is a species signature of Staphylococcus aureus, and discriminates it from most other members of the genus. Inactivation of the gene mtlD, encoding Mtl-1-P dehydrogenase was found to markedly reduce survival in the presence of the antimicrobial fatty acid, linoleic acid. We demonstrate that the sugar alcohol has a potentiating action for this membrane-acting antimicrobial. Analysis of cellular metabolites revealed that, during exponential growth, the mtlD mutant accumulated high levels of Mtl and Mtl-P. The latter metabolite was not detected in its isogenic parent strain or a deletion mutant of the entire mtlABFD operon. In addition, the mtlD mutant strain exhibited a decreased MIC for H2O2, however virulence was unaffected in a model of septic arthritis.
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Liverpool, Merseyside, United Kingdom.
authors.forename: John G
authors.initials: JG
authors.lastname: Kenny
authors.forename: Josephine
authors.initials: J
authors.lastname: Moran
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Kolar
authors.forename: Alexander
authors.initials: A
authors.lastname: Ulanov
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Shaw
authors.forename: Elisabet
authors.initials: E
authors.lastname: Josefsson
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Horsburgh
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019787:Linoleic Acid / Q000494:pharmacology; D008353:Mannitol / Q000378:metabolism*; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D009154:Mutation; D009876:Operon; D012867:Skin / Q000382:microbiology*; D013207:Staphylococcal Skin Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D013401:Sugar Alcohol Dehydrogenases / Q000172:deficiency / Q000235:genetics*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D008353:Mannitol; D019787:Linoleic Acid; D006861:Hydrogen Peroxide; D013401:Sugar Alcohol Dehydrogenases; C077257:mannitol-mannose 1-oxidoreductase