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BrpA in Virulence Modulation of Streptococcus mutans

BrpA 在变形链球菌毒力调节中的作用

基本信息

批准号：
9118974
负责人：
ZEZHANG TOM WEN
金额：
$ 39.57万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9118974
关键词：
ATP phosphohydrolase Affinity Amino Acids Animals Binding Sites Biochemical Biogenesis Biological Assay Cellular biology Centers for Disease Control and Prevention (U.S.)Childhood Communicable Diseases Complex Consensus Defect Dental Plaque Dental caries Development Disease Elements Family Formulation Fumarates Functional disorder Gene Fusion Gene Targeting Genes Goals Gram-Positive Bacteria Health Health Care Costs Homeostasis Human Infection Lesion Mediating Microbial Biofilms Modeling Molecular Mutagenesis Mutation Nature Nitrate Reductases Oxidative Stress Pathogenesis Pathogenicity Pharmacotherapy Phosphotransferases Play Predisposition Prevention Prevention strategy Production Protein Family Proteins Rattus Recombinants Regulation Reporter Reporter Genes Repression Role Seminal Serine Site Streptococcus Streptococcus mutans Tail Techniques Testing Therapeutic Threonine Trans-Activators United States Vaccination Virulence Waxes acid stress antimicrobial base cariogenic bacteria cell envelope combat coping cost design functional genomics genetic regulatory protein killings member mutant novel oral bacteria pathogen promoter response small molecule inhibitor stress tolerance tooth surface trait yeast two hybrid system

项目摘要

DESCRIPTION (provided by applicant): Despite substantial progress in prevention and treatment, dental caries, commonly known as tooth decay or cavities, remains one of the most common and costly infectious diseases worldwide. According to the CDC, associated health care costs more than 80 billion dollars annually, and the rates of childhood caries in the United States are rising. Novel, comprehensive strategies are needed to effectively combat caries pathogenesis. Cariogenic bacteria form tenacious biofilms on the surface of teeth known as dental plaque. Supported by R01 DE019452, we have over the past five years generated seminal evidence that biofilm regulatory protein BrpA, a member of the LytR-CpsA-Psr family of cell envelope associated proteins, plays a critical role in regulation of cell envelope biogenesis and biofilm formation by Streptococcus mutans. The overall goals of this continuation are to elucidate how BrpA regulates S. mutans stress tolerance response and biofilm formation, traits critical to pathogenicity of this key etiological agent of human dental caries, and to explore the potential of targeting BrpA in strategy against S. mutans and dental caries. In this study, we will use an integrative approach that includes modern molecular and biochemical techniques, such as yeast two-hybrid system, and traditional animal caries model (i) to elucidate the mechanisms that govern the expression of this important streptococcal protein, (ii) to identify protein(s) tha interact with BrpA and uncover how BrpA regulates S. mutans pathophysiology, and (iii) to determine the effects of disrupting BrpA on the ability of S. mutans to colonize the tooth surface and cause carious diseases. Elucidation of cis- and trans-acting factors involved in regulation of BrpA expression and uncovering of proteins interactive with BrpA and their roles in BrpA-mediated functions will constitute a major breakthrough in our understanding of not only just BrpA, but also the LCP family of proteins in regulation of cellular biology in S. mutans and other Gram-positive bacteria. Such findings are expected to facilitate the formulation/development of novel comprehensive strategies against tooth decay and potentially other infections caused by Gram-positive bacteria.