Characterizing the Roles of Staphylococcus Aureus Secreted Factors in Virulence and Modulation of Innate Immune Cell Activity

Staphylococcus aureus is a prominent human pathogen that is responsible for a massive burden on healthcare. This thesis takes two approaches to characterize how S. aureus secreted factors subvert the innate immune response. First, characterization of the integral membrane protease 1984 showed that it regulates secretion of a putative lytic transglycosylase, IsaA, which is implicated in virulence. My results suggest IsaA and 1984 are capable of modulating immune responses that result in enhanced heart colonization in vivo. In addition, recent studies have uncovered TLR-independent pathways that induce inflammatory responses after S. aureus insult. Therefore, I hypothesized the bacterium secretes factors capable of modulating non-TLR inflammatory mechanisms. I identified 50 mutants that enhance MyD88-/- macrophage secretion of IL-1β and IL-13. Together, this work provides further evidence for S. aureus mediated innate immune subversion and may aid in furthering our understanding of survival of S. aureus within hostile host environments