Jeffrey Wang Rose Hills
Investigating Cbpb's Role in Bacterial Stringent Response
Cyclic di-AMP (c-di-amp) is a nucleotide second messenger molecule with an integral role in the pathogenesis of many bacteria; however the physiological roles of this molecule in bacteria have only recently begun to be understood. Bacteria are known to undergo physiological and regulatory changes in response to nutrient starvation. Starvation induces the stringent response, which is controlled by the key alarmone molecule (p)ppGpp and is involved in mediating downstream biological processes including antibiotic tolerance, ribosome hibernation, and activating virulence genes. While depletion of c-di-amp and consequent elevation of intracellular (p)ppGpp levels is highly conserved in bacteria, the link between these two signaling molecules is still unclear. I intend to investigate the cross-talk between these molecules by characterizing the protein-protein interactions of CbpB, a c-di-amp-binding protein that regulates the stringent response in Listeria monocytogenes via a bacterial two hybrid screen, followed with proteomic analysis. Investigating this pathway of bacterial stringent response has important implications for understanding the survival mechanisms of bacteria and the pathogenicity of bacteria including virulence gene expression and development of antibiotic tolerance.