The proposed research aims to investigate the genetic and biochemical mechanisms of gene regulation in Streptococcus mutans through the irvA-dependent pathway. The goals of this project will be achieved in three aims by: 1) Analyzing the mechanism of irvA induction 2) Identifying the IrvA regulon 3) Characterizing the genetic regulators that comprise the irvA-dependent pathway. 1) To analyze the mechanism of irvA induction, we will perform detailed biochemical studies of key residues of SMu1275 to determine how its endogenous autocleavage capacity can modulate its ability to control irvA expression. 2) To identify the IrvA regulon, we will employ chromatin immunoprecipitation and microarray (ChIP-chip). Using specially designed Affymetrix Genechips(R), we will be able to detect most or all of the IrvA binding sites in vivo. Transcription analysis of these genes will determine the role of IrvA as a transcription regulator of genes associated with stress and virulence related phenotypes. 3) To characterize the genetic regulators of the irvA-dependent pathway, we will first identify the genes that are capable of inducing irvA. Genetic analyses will then examine the role of irvA as a mediator of stress and virulence related phenotypes in these strains. Finally, genes coregulated with the irvA-dependent pathway will be identified. The goal of this project is to use the irvA-dependent pathway as a model to examine the connection between stress adaptation and the regulation of important virulence factors of Streptococcus mutans. Since the long-term persistence of S. mutans requires the coordination of stress response mechanisms and virulence factor gene expression, these data may yield new insights into S. mutans cariogenicity.

Public Health Relevance

Dental caries is the most common human bacterial disease and is largely correlated with the overgrowth of Streptococcus mutans. Since this organism's ability to cause disease requires careful coordination of its stress response and virulence, these studies may yield novel treatment strategies to control the pathogenesis of S. mutans.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Oklahoma Health Sciences Center
Schools of Dentistry
Oklahoma City
United States
Zip Code
Cheng, Xingqun; Redanz, Sylvio; Cullin, Nyssa et al. (2018) Plasticity of the Pyruvate Node Modulates Hydrogen Peroxide Production and Acid Tolerance in Multiple Oral Streptococci. Appl Environ Microbiol 84:
Zou, Zhengzhong; Qin, Hua; Brenner, Amanda E et al. (2018) LytTR Regulatory Systems: A potential new class of prokaryotic sensory system. PLoS Genet 14:e1007709
Redanz, Sylvio; Cheng, Xingqun; Giacaman, Rodrigo A et al. (2018) Live and let die: Hydrogen peroxide production by the commensal flora and its role in maintaining a symbiotic microbiome. Mol Oral Microbiol 33:337-352
Sadeghinejad, Lida; Cvitkovitch, Dennis G; Siqueira, Walter L et al. (2017) Mechanistic, genomic and proteomic study on the effects of BisGMA-derived biodegradation product on cariogenic bacteria. Dent Mater 33:175-190
Kreth, J; Giacaman, R A; Raghavan, R et al. (2017) The road less traveled - defining molecular commensalism with Streptococcus sanguinis. Mol Oral Microbiol 32:181-196
Liu, Nan; Chaudhry, Muhammad T; Xie, Zhoujie et al. (2017) Identification of New Degrons in Streptococcus mutans Reveals a Novel Strategy for Engineering Targeted, Controllable Proteolysis. Front Microbiol 8:2572
Itzek, A; Chen, Z; Merritt, J et al. (2017) Effect of salivary agglutination on oral streptococcal clearance by human polymorphonuclear neutrophil granulocytes. Mol Oral Microbiol 32:197-210
Chen, Z; Mashburn-Warren, L; Merritt, J et al. (2017) Interference of a speB 5' untranslated region partial deletion with mRNA degradation in Streptococcus pyogenes. Mol Oral Microbiol 32:390-403
Zhang, Shan; Zou, Zhengzhong; Kreth, Jens et al. (2017) Recombineering in Streptococcus mutans Using Direct Repeat-Mediated Cloning-Independent Markerless Mutagenesis (DR-CIMM). Front Cell Infect Microbiol 7:202
Knapp, Steven; Brodal, Clint; Peterson, John et al. (2017) Natural Competence Is Common among Clinical Isolates of Veillonella parvula and Is Useful for Genetic Manipulation of This Key Member of the Oral Microbiome. Front Cell Infect Microbiol 7:139

Showing the most recent 10 out of 30 publications