Metabolic Adaptation Drives Staphylococcus aureus Colonization and Infection of the Skin

Staphylococcus aureus is the most common cause of skin and soft tissue infection, yet the genetic changes in these organisms associated with adapation to human skin are not well characterized. Using S. aureus strains isolated from patients with atopic dermatitis (AD) 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 AD strains activated glycolysis, HIF-α, and 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 typical AD isolate failed to generate protection from a secondary infectious challenge. Within the context of human skin, there is selection for S. aureus metabolic adaptive changes that both promote glycolysis and maintain pathogenicity.