Intra- and interspecies communication in oral bacteria

口腔细菌的种内和种间通讯

基本信息

批准号：
7897920
负责人：
DONALD R DEMUTH
金额：
$ 35.34万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-02-01 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7897920
关键词：
Actinobacillus actinomycetemcomitans Address Adult Affinity Aldehyde-Lyases Bacteria Cell Communication Cell Density Cell physiology Cells Communication Communities Complex DNA Binding Data Dental Plaque Dependency Detection Development Dose Environment Enzymes Escherichia coli Event Expenditure Feedback Funding Gene Expression Gene Mutation Genes Gingival Pocket Goals Growth Growth and Development function Heart Diseases Helix-Turn-Helix Motifs Hemin Hybrids Individual Iron Kinetics Lead Life Link Mediating Microbial Biofilms Modeling Molecular Monitor Mouth Diseases Nutrient Operon Oral Oral cavity Organism Outcome Pathway interactions Periodontal Diseases Periodontitis Pharmaceutical Preparations Phosphotransferases Population Porphyromonas gingivalis Prevention Process Promoter Regions Proteins Regulator Genes Reporting Salmonella Sampling Series Signal Transduction Site Solutions System Testing Therapeutic Intervention Transport Process United States VAI-2 Vibrio Virulence Virulence Factors design microbial microbial community mutant novel therapeutics oral bacteria oral biofilm oral pathogen pathogen prevent promoter public health relevance quorum sensing receptor response sensor uptake

项目摘要

DESCRIPTION (provided by applicant): Periodontal disease is caused by bacterial pathogens that thrive in a complex multi-species community that forms in the gingival pocket. The initiation and growth of this biofilm requires sophisticated molecular communication among the species in this community. We have shown that the periodontal pathogens A. actinomycetemcomitans and P.gingivalis produce the quorum sensing signal autoinducer2 (AI-2) which may be involved in intra- and interspecies communication among these organisms. AI-2 regulates genes involved in virulence, iron acquisition and biofilm formation and is likely an important mechanism that allows these organisms to sense and respond to their local environment. Our general hypothesis that A. actinomycetemcomitans and P. gingivalis respond differentially to AI-2 and the outcomes of these signaling systems are tailored to the specific survival strategies that are employed by these organisms in the oral biofilm. The long term goal of this proposal is to determine if AI-2 quorum sensing can be exploited to control oral biofilm development. The specific aims are to characterize the AI-2 receptors and early events that initiate the cellular response to AI-2 of A. actinomycetemcomitans and P. gingivalis since these are ideal targets for therapeutic intervention. We will determine if importation and intracellular processing of AI-2 is required to initiate the cellular response. The QseBC and GppX two component signaling systems of A. actinomycetemcomitans and P. gingivalis respectively, will be studied to determine if they couple the detection of AI-2 to downstream gene regulatory events. Finally, we will determine if the function of high and low affinity AI-2 receptors in A. actinomycetemcomitans facilitate colonization of both early and mature biofilms by this organism. These studies will define at the molecular level how oral pathogens detect and interact with AI-2 and how these processes lead to alteration in gene expression that facilitates their growth in microbial communities. This information may facilitate the rational design of new therapeutics that may control the growth and development of oral microbial biofilms by interfering with their communication pathways. PUBLIC HEALTH RELEVANCE: Periodontitis is a common oral disease that is present in up to 40% of the adult population in the United States and annual expenditures for treatment and prevention of periodontitis are over $14 billion. Periodontitis caused by a community of bacteria that live in the gingival pocket, but it is also associated with systemic illnesses such as heart disease. Preventing periodontal disease requires eliminating or controlling the microbial community. Our studies examine a unique microbial communication pathway that facilitates the development of the bacterial community. We seek to develop new potential drugs that prevent the formation of microbial communities by interfering with this communication system in order to control or prevent periodontitis.