The Role of Staphylococcus aureus SasD in Lung

总结

SUMMARY Despite intense research focus, Staphylococcus aureus has remained an important cause of both community acquired pneumonia and viral-related super-infections. The field has recently determined host mediated mechanisms induced by S. aureus that drive lung infection and injury. In the context of preceding influenza infection, our group and many others have delineated aberrant immune pathway regulation as key drivers of S. aureus susceptibility and pathogenesis. In addition to host mediated interactions, S. aureus expresses a number of secreted and cell wall virulence factors that have not been fully characterized in pulmonary infection. We performed a transposon mutant screen of S. aureus cell wall anchored proteins in pulmonary infection and super- infection in mice. This screen revealed a novel S. aureus virulence factor, SasD, which is required for lung inflammation, injury, and mortality. SasD was also required for lung epithelial cell attachment and inflammatory cytokine induction by macrophages. In this application, we hypothesize that S. aureus SasD is a critical virulence factor in pulmonary infection, which mediates bacterial adherence to the lung stroma and interactions with primary lung phagocytes. We will test this hypothesis with two independent, but related Aims; 1) investigate the role of SasD in bacterial adhesion to lung epithelial cells and in vivo growth in the lung, 2) examine the role of SasD in mediating S. aureus interaction with pulmonary phagocytes and the impact on lung inflammation. We will determine the context dependent roles of S. aureus SasD in single and influenza super-infection. Further, we will utilize cutting edge tools to determine these interactions in human and mouse systems. Data generated in this project will inform upon focusing on S. aureus SasD at a potential therapeutic or vaccine target in pulmonary infections.