Bose Pilot Project Summary

Previously, we identified the fatty acid kinase of methicillin-resistant Staphylococcus aureus (MRSA) as a contributor to the production of key virulence factors. Absence of the kinase leads to enhanced necrosis and altered immune signals in a murine model of skin infection. One observed cytokine difference was IL-17, a key immune response modulator that is produced by many cells types and has been shown to be important to S. aureus infection resolution. However, it is not known what immune cells are present and important for the observed changes in immune signals or whether this is due directly to altered IL-17 abundance. As a first step, we seek to identify the immune cells present at the site of infection and which cells make IL-17. This will be done using antibodies directed at different immune cell markers and flow cytometry from infected skin homogenates. In addition, we will use computational modeling and docking to develop analogs for proteinligand binding assays as well potential small molecule inhibitors. The results of these studies will shed light on the enhanced virulence of a fatty acid kinase mutant, provide a comprehensive view of immunological factors present during S. aureus skin infection, and be the first step toward developing novel molecules to target S. aureus fatty acid kinase.