Functional genomic analyses of a peptide antibiotic-sensing and response regulon in Streptococcus mutans

Tooth decay or caries is one of the most common human diseases, affecting over 80% of young people worldwide. By the age 70, more than 25% of populations may have lost some or all of their natural teeth due to tooth decay. Children and adults receiving chemotherapy for cancer, AIDS or other systemic diseases are notably at higher risk for caries. Although caries is not a life-threatening disease, diagnosing, treating and retreating caries and caries-related diseases is still a major financial burden to the public health systems worldwide. In many undeveloped regions and countries, tooth decay remains a "silent epidemic" left untreated. Tooth decay is caused by bacteria living in the oral cavity. One bacterium called Streptococcus mutans is considered as a leading cariogenic pathogen worldwide, because this bacterium is highly efficient to express several virulence-associated traits, of which the ability of this bacterium to survive and adapt to killing by host defense peptides or by antibiotics is a prerequisite for its persistence in the oral cavity. Such an ability may provide this bacterium with an overwhelming ecological advantage, resulting in an emergence of significant number of this bacterium that may initiate tooth decay. Our understanding of molecular mechanisms of how this bacterium adapts to antibiotics and initiates tooth decay is still lacking. This requires new knowledge and experimental approaches to explore these questions. In this project, we propose to develop innovative approaches to investigate these questions. The data obtained from this project will contribute to the body of knowledge that facilitates our understanding of how this bacterium adapts to peptide antibiotics and the mechanisms in which the bacterium initiates tooth decay. The knowledge obtained from this research will allows us to develop new strategies to prevent tooth decay.