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（由申请人提供）：牙周疾病是由细菌病原体引起的，这些病原体在形成牙龈袋中形成的复杂多物种社区中壮成长。该生物膜的起始和生长需要该社区中该物种之间进行复杂的分子通信。我们已经表明，牙周病原体A.放线菌和吉利亚病产生了可能与这些生物体之间的种内和种间通信有关的群体传感信号自动诱导器2（AI-2）。 AI-2调节涉及毒力，采集和生物膜形成的基因，并且可能是一种重要的机制，使这些生物可以感知并对其当地环境做出反应。我们的一般假设是，放线杆菌和牙龈疟原虫对AI-2的反应有所不同，并且这些信号系统的结果是针对这些生物体在口腔生物膜中采用的特定生存策略量身定制的。该提案的长期目标是确定是否可以利用AI-2法定人数传感来控制口腔生物膜的发展。具体的目的是表征AI-2受体和早期事件，这些受体启动了对放线杆菌的AI-2的细胞反应和牙龈疟原虫，因为这些是治疗干预的理想靶标。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。将研究QSEBC和GPPX的两个成分信号传导系统，分别研究放线杆菌和牙龈疟原虫，以确定它们是否将AI-2的检测与下游基因调节事件相结合。最后，我们将确定该生物体的早期和成熟生物膜的高亲和力AI-2受体的高和低亲和力AI-2受体的功能。这些研究将在分子水平上定义口腔病原体如何检测和与AI-2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。这些信息可能会促进新治疗剂的合理设计，这些设计可能通过干扰其通信途径来控制口腔微生物生物膜的生长和发展。公共卫生相关性：牙周炎是一种常见的口腔疾病，在美国多达40％的成年人口中存在，治疗和预防牙周炎的年度支出超过140亿美元。牙周炎是由生活在牙龈袋中的细菌群落引起的，但它也与心脏病等全身性疾病有关。预防牙周疾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通信途径，可促进细菌群落的发展。我们试图开发新的潜在药物，以通过干扰这种通信系统来控制或预防牙周炎，以防止微生物群落形成。