Intra- and interspecies communication in oral bacteria

口腔细菌的种内和种间通讯

• 批准号: 8299184
• 负责人: DONALD R DEMUTH
• 金额: $ 34.98万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8299184
• 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; Health; 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; quorum sensing; receptor; response; sensor; uptake

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.

描述(申请人提供)：牙周病是由细菌病原体引起的，这些细菌在一个复杂的多物种群落中茁壮成长，形成在牙龈袋中。这种生物膜的形成和生长需要在这个群落中的物种之间进行复杂的分子交流。我们已经证明牙周病原体伴生放线杆菌和牙龈假单胞菌产生群体感应信号自动诱导器2(AI-2)，它可能参与这些微生物之间的种内和种间交流。AI-2调控与毒力、铁获取和生物膜形成有关的基因，可能是允许这些生物感知和响应当地环境的重要机制。我们的一般假设是，伴生放线杆菌和牙龈假单胞菌对AI-2的反应不同，这些信号系统的结果是根据这些微生物在口腔生物膜中采用的特定生存策略而定制的。这项提案的长期目标是确定AI-2群体感应是否可以被用来控制口腔生物膜的发育。其具体目的是表征AI-2受体和启动细胞对AI-2的反应的早期事件，因为这些都是治疗干预的理想靶点。我们将确定是否需要AI-2的进口和细胞内处理来启动细胞反应。将对伴生放线杆菌和牙龈假单胞菌的两个信号系统QseBC和GppX进行研究，以确定它们是否将AI-2的检测与下游的基因调控事件联系起来。最后，我们将确定放线菌伴生菌中高亲和力和低亲和力AI-2受体的功能是否促进这种微生物对早期和成熟生物膜的定植。这些研究将在分子水平上定义口腔病原体如何检测AI-2并与其相互作用，以及这些过程如何导致基因表达的改变，从而促进它们在微生物群落中的生长。这些信息可能有助于合理设计新的治疗方法，通过干扰口腔微生物生物膜的通讯途径来控制其生长和发展。公共卫生相关性：牙周炎是一种常见的口腔疾病，在美国高达40%的成年人中存在，每年用于牙周炎治疗和预防的支出超过140亿美元。牙周炎是由牙周袋中的细菌群落引起的，但它也与心脏病等全身疾病有关。预防牙周病需要消除或控制微生物群落。我们的研究检查了一种独特的微生物交流途径，它促进了细菌群落的发展。我们寻求开发新的潜在药物，通过干扰这种通讯系统来防止微生物群落的形成，以控制或预防牙周炎。