Staphylococcus aureus wall teichoic acid structure dictates virulence potential and resistance to host defenses.

Staphylococcus aureus is a formidable pathogen and the leading cause of skin and soft tissue infections. We recently showed that the highly conserved sasF gene, encoding for an uncharacterized sortase-anchored surface protein, is up-regulated when S. aureus colonizes skin. Here, we demonstrate that SasF is an enzyme that has glycoside epimerase activity, which is required for S. aureus resistance to skin fatty acids. Mutants of sasF are highly impaired in skin colonization and acute infection models. The SasF enzyme is crucial for maintaining the structure of wall teichoic acids and proper S. aureus surface chemistry. To our knowledge, this is the first report of a bacterial surface epimerase in this pathogen, suggesting that SasF could be a therapeutic target.