Bose, Jeffrey LDeMars, Zachary2021-07-202021-07-202021-05-312021http://dissertations.umi.com/ku:17652https://hdl.handle.net/1808/31767Staphylococcus aureus can utilize exogenous fatty acids for phospholipid synthesis. The fatty acid kinase FakA is essential for this utilization by phosphorylating exogenous fatty acids for incorporation into lipids. How exogenous fatty acid utilization from the environment via FakA affects the composition and function of the phospholipid membrane, central metabolism, and virulence factor regulation is not well understood. We found that inactivation of the exogenous fatty acid utilization system through genetic deletion of fakA resulted in a membrane that is more rigid than membranes of wild-type S. aureus. Central metabolism, particularly the production and consumption of acetate, was significantly altered resulting in a more oxidized cellular environment when fakA was deleted. Both the accumulation of free fatty acids within the cell of a fakA mutant and the presence of exogenous fatty acids in the growth medium decrease virulence factor production through the transmembrane domains of the two-component system SaeRS. In summary, we identified previously unknown roles for the exogenous fatty acid utilization system in maintaining membrane and metabolic homeostasis in addition to expanding our mechanistic understanding of how fatty acids negatively influence virulence factor expression.210 pagesenCopyright held by the author.Microbiologyfatty acidsmetabolismPhospholipidtwo-component systemDissertationhttps://orcid.org/0000-0003-4501-8223openAccess