Mannitol utilisation is required for protection of Staphylococcus aureus from human skin antimicrobial fatty acids

• Published in: PloS one 2013-07, Vol.8 (7), p.e67698
• Main Authors: Kenny, John G, Moran, Josephine, Kolar, Stacey L, Ulanov, Alexander, Li, Zhong, Shaw, Lindsey N, Josefsson, Elisabet, Horsburgh, Malcolm J
• Format: Article
• Language: English
• Subjects: ABSCESSES; Alcohols; Animals; ANTIBACTERIAL ACTIVITY; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; Arthritis; BACILLUS-SUBTILIS; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biology; Carotenoids; Cell and Molecular Biology; Cell- och molekylärbiologi; Charged particles; Clonal deletion; Deactivation; Dehydrogenases; Deletion mutant; EXPRESSION; Fatty acids; Fermentation; Gene Expression Regulation, Bacterial; Genes; Humans; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; IN-VIVO; Inactivation; Linoleic acid; Linoleic Acid - pharmacology; LIPIDS; Mannitol; Mannitol - metabolism; Medicine; Metabolism; Metabolites; Mice; Microbial Sensitivity Tests; Microbial Viability - drug effects; Minimum inhibitory concentration; Molecular biology; Mutation; Operon; OXIDATIVE; Oxidative stress; Plasmids; Skin; Skin - microbiology; Staphylococcal Skin Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - growth & development; Staphylococcus aureus - metabolism; STARVATION; STRESS; STRESS RESISTANCE; Sugar; Sugar Alcohol Dehydrogenases - deficiency; Sugar Alcohol Dehydrogenases - genetics; VIRULENCE
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0067698

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.