Mannitol Utilisation is Required for Protection of <i>Staphylococcus aureus</i> from Human Skin Antimicrobial Fatty Acids

<div><p>Mannitol (Mtl) fermentation, with the subsequent production of acid, is a species signature of <i>Staphylococcus aureus</i>, and discriminates it from most other members of the genus. Inactivation of the gene <i>mtlD,</i> 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 <i>mtlD</i> 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 <i>mtlABFD</i> operon. In addition, the <i>mtlD</i> mutant strain exhibited a decreased MIC for H₂O₂, however virulence was unaffected in a model of septic arthritis.</p>