The Streptococcus mutans rcrRPQ gene products govern stress tolerance, biofilm formation and (p)ppGpp accumulation. Importantly, the RcrR transcriptional regulator and RcrPQ ABC efflux pumps dominantly control genetic competence and cellular responses to intercellular peptide signal molecules. We have discovered two peptides encoded at the 3' end of the rcrQ gene that function as negative effectors of competence, as well as a small protein (named ComX2) encoded entirely within the comX gene that can disrupt comX transcription, destabilize the ComX protein and render cells sensitive to oxidative stress. The purpose of this study is to understand the molecular mechanisms by which these newly discovered effector molecules regulate responses to environmental stress and integrate the physiologic status of the cells into the decision networks that control competence development and modulate the pathogenic potential of the organism. To achieve these goals, the following aims are outlined:
Aim 1. Determine the mechanisms by which rcrQ-encoded peptides and ComX2 impact rcrRPQ, comX and comX2 transcription, and the stability of the ComX protein.
Aim 2. Employ metabolomics to explore the localization of rcrQ-encoded peptides and ComX2, and to analyze the composition of supernatant fluids of specific genetically modified strains.
Aim 3. Examine how (p)ppGpp metabolism and the RelA enzyme integrate stress and competence development by controlling the phenotypic behaviors of certain rcrRPQ mutants.
The bacteria that cause oral diseases must be able to tolerate environmental stresses in the form of low pH, harmful oxygen radicals and deprivation for nutrients. The research conducted here examines the way in which bacteria regulate gene expression in response to environmental cues to optimize their ability to cause disease. Using state-of- the-art technologies, new targets for therapies to prevent or treat oral diseases and other infections in humans are being identified.
Showing the most recent 10 out of 71 publications
