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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE013239-19
Application #
9298620
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
1999-09-01
Project End
2020-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
19
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Florida
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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Liu, Yuan; Palmer, Sara R; Chang, Hsiaochi et al. (2018) Differential oxidative stress tolerance of Streptococcus mutans isolates affects competition in an ecological mixed-species biofilm model. Environ Microbiol Rep 10:12-22
Burne, R A (2018) Getting to Know ""The Known Unknowns"": Heterogeneity in the Oral Microbiome. Adv Dent Res 29:66-70
Kaspar, Justin; Shields, Robert C; Burne, Robert A (2018) Competence inhibition by the XrpA peptide encoded within the comX gene of Streptococcus mutans. Mol Microbiol 109:345-364
Underhill, Simon A M; Shields, Robert C; Kaspar, Justin R et al. (2018) Intracellular Signaling by the comRS System in Streptococcus mutans Genetic Competence. mSphere 3:
Zeng, Lin; Chen, Lulu; Burne, Robert A (2018) Preferred Hexoses Influence Long-Term Memory in and Induction of Lactose Catabolism by Streptococcus mutans. Appl Environ Microbiol 84:
Son, M; Kaspar, J; Ahn, S J et al. (2018) Threshold regulation and stochasticity from the MecA/ClpCP proteolytic system in Streptococcus mutans competence. Mol Microbiol 110:914-930
De Furio, Matthew; Ahn, Sang Joon; Burne, Robert A et al. (2017) Oxidative Stressors Modify the Response of Streptococcus mutans to Its Competence Signal Peptides. Appl Environ Microbiol 83:
Shields, Robert C; O'Brien, Greg; Maricic, Natalie et al. (2017) Genome-wide screens reveal new gene products that influence genetic competence in Streptococcus mutans. J Bacteriol :
Kaspar, Justin; Underhill, Simon A M; Shields, Robert C et al. (2017) Intercellular communication via the comX-Inducing Peptide (XIP) of Streptococcus mutans. J Bacteriol :

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