The proposed research aims to investigate the molecular mechanisms used by the irvR/A regulatory system of Streptococcus mutans to control numerous accessory gene pathways in response to environmental stress. Our previous studies demonstrated that the central regulator of this system irvA is a riboregulatory mRNA. Its principal regulatory function is mediated through seed pairing with irvA mRNA, rather than through the function of its encoded protein. Such regulatory control is a new paradigm for the function of mRNAs. In this project, we are interested to determine the mechanisms used by S. mutans to modulate irvA expression, the role of irvA as a pleiotropic riboregulatory mRNA, and the ability of irvA to exploit the regulatory ribonuclease RNase J2 for the posttranscriptional control of gene expression. The goals of the project will be completed in three Aims. 1) To determine the mechanism controlling irvA expression, we will characterize the protein-protein interactions that modulate the stability and function of the proximal regulator of irvA gene expression, IrvR. This mechanism will be tested for its role in modulating biofilm integrity during environmental stress. 2) To understand the role of irvA as a pleiotropic riboregulatory mRNA, we will identify the overlapping geneset between the irvA regulon and a newly identified RNA chaperone required for irvA riboregulation. These genes will be tested for irvA- and chaperone-dependent regulation of target mRNA stability and seed pairing. 3) To investigate the ability of irvA to exploit RNase J2 for the control of gene expression, we will test irvA and RNA chaperone for their ability to modulate RNase J2 degradation of irvA target mRNAs via seed pairing. We will also determine the recognition elements in RNA that specify cleavage by RNase J2. The proposed studies will provide some of the first mechanistic insights into the posttranscriptional regulatory mechanisms used by oral bacteria and will demonstrate how key pathways are regulated in response to environmental stress. This will hopefully add an important layer to our understanding of S. mutans ability to influence oral ecology.

Public Health Relevance

Dental caries is one of the most common diseases worldwide and Streptococcus mutans is among the most frequently detected organisms in caries lesions. This study aims to understand S. mutans role in the pathogenesis of caries by focusing upon its ability to regulate virulence in response to environmental stress.

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
Oregon Health and Science University
Schools of Dentistry/Oral Hygn
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