Oral bacteria exist as compositionally and structurally complex populations in biofilms colonizing the tissues of the mouth. In most cases, oral biofilms are compatible with health. It is perturbations caused by environmental stresses that induce the changes in the composition and metabolic activities of biofilm bacteria that lead to the initiation and progression of oral diseases. The overall goals of the proposal are to provide detailed molecular and physiologic information about the capacity of oral bacteria to form and persist in biofilms, with particular focus on environmental stresses that can modulate the virulence of oral bacteria and enhance the pathogenic potential of oral biofilms. To achieve these goals, the following aims are outlined:
Aim 1. Analyze the molecular basis for post-transcriptional control of dnaK operon expression and stress tolerance in S. mutans.
Aim 2. Determine the role of (p)ppGpp in physiologic homeostasis, growth and survival decisions, and virulence expression in exponentially-growing S. mutans.
Aim 3. Dissect the molecular basis for stress tolerance and modulation of relP expression by a MarR transcriptional regulator and two ATP binding cassette exporters. By implementing the research plan, we will disclose fundamental details about the intimate linkage of stress tolerance with the ability of this organism to form biofilms on surfaces of the oral cavity. The research will provide the scientific community with an array of information that can be used to develop novel and more effective strategies to prevent and treat oral diseases and other debilitating human infectious diseases.

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 their environment 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 #
5R01DE013239-14
Application #
8270373
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
1999-09-01
Project End
2015-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
14
Fiscal Year
2012
Total Cost
$344,458
Indirect Cost
$109,333
Name
University of Florida
Department
Dentistry
Type
Schools of Dentistry
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Shields, Robert C; Burne, Robert A (2016) Growth of Streptococcus mutans in Biofilms Alters Peptide Signaling at the Sub-population Level. Front Microbiol 7:1075
Kaspar, Justin; Kim, Jeong N; Ahn, Sang-Joon et al. (2016) An Essential Role for (p)ppGpp in the Integration of Stress Tolerance, Peptide Signaling, and Competence Development in Streptococcus mutans. Front Microbiol 7:1162
Kim, Jeong Nam; Ahn, Sang-Joon; Burne, Robert A (2015) Genetics and Physiology of Acetate Metabolism by the Pta-Ack Pathway of Streptococcus mutans. Appl Environ Microbiol 81:5015-25
Kaspar, Justin; Ahn, Sang-Joon; Palmer, Sara R et al. (2015) A unique open reading frame within the comX gene of Streptococcus mutans regulates genetic competence and oxidative stress tolerance. Mol Microbiol 96:463-82
Palmer, Sara R; Burne, Robert A (2015) Post-transcriptional regulation by distal Shine-Dalgarno sequences in the grpE-dnaK intergenic region of Streptococcus mutans. Mol Microbiol 98:302-17
Seaton, K; Ahn, S-J; Burne, R A (2015) Regulation of competence and gene expression in Streptococcus mutans by the RcrR transcriptional regulator. Mol Oral Microbiol 30:147-59
Son, Minjun; Shields, Robert C; Ahn, Sang-Joon et al. (2015) Bidirectional signaling in the competence regulatory pathway of Streptococcus mutans. FEMS Microbiol Lett 362:
Son, Minjun; Ghoreishi, Delaram; Ahn, Sang-Joon et al. (2015) Sharply Tuned pH Response of Genetic Competence Regulation in Streptococcus mutans: a Microfluidic Study of the Environmental Sensitivity of comX. Appl Environ Microbiol 81:5622-31
Mogen, Austin B; Chen, Fu; Ahn, Sang-Joon et al. (2015) Pluronics-Formulated Farnesol Promotes Efficient Killing and Demonstrates Novel Interactions with Streptococcus mutans Biofilms. PLoS One 10:e0133886
Shields, Robert C; Burne, Robert A (2015) Conserved and divergent functions of RcrRPQ in Streptococcus gordonii and S. mutans. FEMS Microbiol Lett 362:

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