Pathogens in biofilms are more resistant to harsh environmental stresses such as antibiotics and the host immune system. Prevention of biofilm formation is critical to advancing therapeutic treatments against infectious diseases. Oral biofilm is important for periodontal diseases in which pioneers provide substrates allowing colonization of subsequent pathogens. Oral bacterial interactions, especially coaggregation between pioneering colonizers (such as mitis group streptococci, MGS) and pathogenic species (such as Porphyromonas gingivalis or Fusobacterium nucleatum), are important for periodontal diseases. We have identified a Streptococcus sanguinis two-component system (TCS) gene that is responsible for increased adherence with P. gingivalis and F. nucleatum. We propose an integrative study of this TCS regulon and related gene functions by systems biology. To characterize the TCS regulon, the gene expression profiles will be examined using microarray technology. The DNA binding sites will be identified by ChIP-seq. To examine gene functions in biofilm, the TCS regulated gene mutants will be collected from a comprehensive gene mutant library. Bacterial interaction of these mutants with oral pathogens will be systematically examined to identify biofilm genes by confocal microscopy. The biological functions of these genes will be studied as a whole to understand the relationship of the TCS and the biofilm genes.

Public Health Relevance

Oral biofilms are important for periodontal diseases. Pathogens in biofilms are more resistant to harsh environmental stresses and clinical treatments. We propose an integrative study of streptococcal biofilm genes to advance therapy against infectious diseases.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Oral, Dental and Craniofacial Sciences Study Section (ODCS)
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Lunsford, Dwayne
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Virginia Commonwealth University
Schools of Dentistry
United States
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Ge, Xiuchun; Yu, Yang; Zhang, Min et al. (2016) Involvement of NADH Oxidase in Competition and Endocarditis Virulence in Streptococcus sanguinis. Infect Immun 84:1470-7
Ge, Xiuchun; Shi, Xiaoli; Shi, Limei et al. (2016) Involvement of NADH Oxidase in Biofilm Formation in Streptococcus sanguinis. PLoS One 11:e0151142
Chen, Lei; Ge, Xiuchun; Xu, Ping (2015) Identifying essential Streptococcus sanguinis genes using genome-wide deletion mutation. Methods Mol Biol 1279:15-23
Stone, Victoria N; Parikh, Hardik I; El-rami, Fadi et al. (2015) Identification of Small-Molecule Inhibitors against Meso-2, 6-Diaminopimelate Dehydrogenase from Porphyromonas gingivalis. PLoS One 10:e0141126
Crump, Katie E; Bainbridge, Brian; Brusko, Sarah et al. (2014) The relationship of the lipoprotein SsaB, manganese and superoxide dismutase in Streptococcus sanguinis virulence for endocarditis. Mol Microbiol 92:1243-59
Evans, Karra; Stone, Victoria; Chen, Lei et al. (2014) Systematic study of genes influencing cellular chain length in Streptococcus sanguinis. Microbiology 160:307-15
Xu, Ping; Gunsolley, John (2014) Application of metagenomics in understanding oral health and disease. Virulence 5:424-32
Rhodes, DeLacy V; Crump, Katie E; Makhlynets, Olga et al. (2014) Genetic characterization and role in virulence of the ribonucleotide reductases of Streptococcus sanguinis. J Biol Chem 289:6273-87