Streptococcus sanguinis is a common pathogen in endocarditis and a pioneer colonizer of human teeth. In heart tissues, S. sanguinis can cause infective endocarditis, but in the mouth, S. sanguinis is considered a benign or even a beneficial bacterium because the presence of S. sanguinis delays caries caused by S. mutans. A putative global regulator, Mgs, was identified in the recently completed S. sanguinis genome. Genomic analysis has revealed that the Mgs coding gene is a horizontally transferred gene. Real-time quantitative PCR experiments suggest that Mgs regulates several putative virulence genes. The hypothesis is that Mgs is a transcription regulator involved in virulence gene expression in S. sanguinis. The objective of this application is to understand the mechanism of Mgs-mediated gene regulation in endocarditis and its effects on S. sanguinis in the oral community. We propose 1) to identify Mgs-regulated genes;2) to identify Mgs DNA-binding sites and its binding domains;3) to identify relationships among Mgs regulated proteins in silico;and 4) to identify Mgs regulated protein expressions and functions. These analyses will improve our understanding at the molecular level of this regulator and identify new targets for development of strategies, such as chemo- or immunotherapy, against streptococcal endocarditis. PUBLIC HEALTH SIGNIFICANCE: Streptococcus sanguinis is a common pathogen in endocarditis and a pioneer colonizer of human teeth. Endocarditis is a serious, often fatal, infection of the heart. We have compared the S. sanguinis genome with other streptococcal genomes and identified a global regulator, Mgs. We propose to examine Mgs regulation, its DNA binding site, and its function in endocarditis for developing chemotherapeutic or immunotherapeutic strategies against streptococcal endocarditis.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-MOSS-E (02))
Program Officer
Lunsford, Dwayne
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Virginia Commonwealth University
Schools of Dentistry
United States
Zip Code
Xu, Ping; Gunsolley, John (2014) Application of metagenomics in understanding oral health and disease. Virulence 5:424-32
Evans, Karra; Stone, Victoria; Chen, Lei et al. (2014) Systematic study of genes influencing cellular chain length in Streptococcus sanguinis. Microbiology 160:307-15
Trihn, My; Ge, Xiuchun; Dobson, Alleson et al. (2013) Two-component system response regulators involved in virulence of Streptococcus pneumoniae TIGR4 in infective endocarditis. PLoS One 8:e54320
Ge, Xiuchun; Rodriguez, Rafael; Trinh, My et al. (2013) Oral microbiome of deep and shallow dental pockets in chronic periodontitis. PLoS One 8:e65520
Rodriguez, A M; Callahan, J E; Fawcett, P et al. (2011) Physiological and molecular characterization of genetic competence in Streptococcus sanguinis. Mol Oral Microbiol 26:99-116
Chen, Lei; Ge, Xiuchun; Dou, Yuetan et al. (2011) Identification of hydrogen peroxide production-related genes in Streptococcus sanguinis and their functional relationship with pyruvate oxidase. Microbiology 157:13-20
Ge, Xiuchun; Kitten, Todd; Munro, Cindy L et al. (2010) Pooled protein immunization for identification of cell surface antigens in Streptococcus sanguinis. PLoS One 5:e11666
Das, Sankar; Kanamoto, Taisei; Ge, Xiuchun et al. (2009) Contribution of lipoproteins and lipoprotein processing to endocarditis virulence in Streptococcus sanguinis. J Bacteriol 191:4166-79
Ge, Xiuchun; Kitten, Todd; Chen, Zhenming et al. (2008) Identification of Streptococcus sanguinis genes required for biofilm formation and examination of their role in endocarditis virulence. Infect Immun 76:2551-9