Strains of Staphylococcus aureus that colonize and infect skin harbor mutations in metabolic genes

Summary Staphylococcus aureus is the most common cause of skin and soft tissue infection, yet the bacterial genetic changes associated with adaptation to human skin are not well characterized. S. aureus strains isolated from patients with chronic skin colonization and intermittent infection were used to determine the staphylococcal genotypes/phenotypes associated with adaptation to human skin. We demonstrate that polymorphisms in metabolic genes, particularly those involved in the tricarboxylic acid (TCA) cycle, the fumarate/succinate axis, and the generation of terminal electron transporters are unexpectedly common. These skin-adapted strains activated glycolysis, HIF-1α, IL-1β, and IL-18 release from keratinocytes and promoted dermatopathology equivalent to an MRSA USA300 control in a murine model of infection. However, in contrast to USA300, a skin-adapted isolate failed to generate protection from a secondary infectious challenge. Within the context of human skin, there appears to be selection for S. aureus metabolic adaptive changes that promote glycolysis and maintain pathogenicity.