Staphylococcus Aureus Fatty Acid Kinase FakA Modulates Pathogenesis During Skin Infection Via Proteases

fatty acid kinase FakA is necessary for the incorporation of exogenous fatty acids into the lipid membrane. We previously demonstrated that the inactivation of leads to decreased α-hemolysin (Hla) production but increased expression of the proteases SspAB and aureolysin , and that the Δ mutant causes larger lesions than the wild type (WT) during murine skin infection. As expected, necrosis is Hla dependent in the presence or absence of FakA, as both and Δ mutants are unable to cause necrosis of the skin. At day 4 postinfection, while the Δ mutant maintains larger and more necrotic abscesses, bacterial numbers are similar to those of the WT, indicating the enhanced tissue damage of mice infected with the Δ mutant is not due to an increase in bacterial burden. At this early stage of infection, skin infected with the Δ mutant has decreased levels of proinflammatory cytokines, such as interleukin-17A (IL-17A) and IL-1α, compared to those of WT-infected skin. At a later stage of infection (day 7), abscess resolution and bacterial clearance are hindered in Δ mutant-infected mice. The paradoxical findings of decreased Hla but increased necrosis led us to investigate the role of the proteases regulated by FakA. Utilizing Δ and Δ mutants in both the WT and mutant backgrounds, we found that the absence of these proteases in a mutant reduced dermonecrosis to levels similar to those of the WT strain. These studies suggest that the overproduction of proteases is one factor contributing to the enhanced pathogenesis of the Δ mutant during skin infection.