Doctor of Philosophy (PhD)
Pathology & Microbiology
The death and lysis of a subpopulation of cells in Staphylococcus aureus biofilms is thought to benefit the surviving population by releasing extracellular DNA, a critical component of the biofilm extracellular matrix. Although the means by which S. aureus controls cell death and lysis is not completely understood, studies implicate the role of the cidABC, alsSD and lrgAB operons in this process. This dissertation has focused on the regulation of cidABC and alsSD expression, which is mediated, primarily, by the LysR-Type Transcriptional Regulator (LTTR) known as CidR. To better define the role of CidR in regulating cidABC and alsSD transcription we produced a series of mutations in the cidABC and alsSD promoter regions to identify a putative CidR-binding site, TAGTA-N-TACAAA. Although CidR was found to directly interact with this site, these studies also revealed that the induction of cidABC and alsSD transcription is modulated by two other transcriptional regulators, CcpA and SrrAB, linking cidABC and alsSD to carbon catabolite repression and respiration. Perhaps most interestingly, a phenotype associated with the cidB was also identified; disrupting cidB in the srrAB mutant background resulted in a decrease in the levels of ROS and sensitivity to ROS, rescuing stationary phase survival. The results of this study further expand upon the cidABC and alsSD regulatory network of as well as the role this regulon plays in cell death.
Windham, Ian H., "Regulation of cid-mediated cell death in Staphylococcus aureus" (2016). Theses & Dissertations. 98.