Intra- and interspecies communication in oral bacteria

描述（由申请人提供）：牙周病是由细菌病原体引起的，这些细菌病原体在牙龈口袋中形成一个复杂的多物种群落。这种生物膜的形成和生长需要在这个群落的物种之间进行复杂的分子交流。我们发现牙周病原菌放线菌属和牙龈菌属产生群体感应信号autoinducer2 (AI-2)，这可能参与了这些生物之间的种内和种间交流。AI-2调节涉及毒力、铁获取和生物膜形成的基因，可能是这些生物体感知和响应当地环境的重要机制。我们的一般假设是放线菌单胞菌和牙龈单胞菌对AI-2的反应不同，这些信号系统的结果是根据这些生物在口腔生物膜中采用的特定生存策略量身定制的。本提案的长期目标是确定AI-2群体感应是否可以用来控制口腔生物膜的发育。具体的目的是表征AI-2受体和早期事件启动AI-2的细胞反应放线菌和牙龈假单胞菌，因为它们是治疗干预的理想靶点。我们将确定是否需要输入和细胞内处理AI-2来启动细胞反应。我们将分别研究A.放线菌comitans和P. gingivalis的QseBC和GppX两组分信号系统，以确定它们是否将AI-2的检测与下游基因调控事件相结合。最后，我们将确定放线菌A.放线菌中高亲和力和低亲和力AI-2受体的功能是否有助于该生物在早期和成熟生物膜上的定植。这些研究将在分子水平上确定口腔病原体如何检测并与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。这一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它们的生长和发育。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，每年用于治疗和预防牙周炎的支出超过140亿美元。牙周炎是由生活在牙龈袋中的一群细菌引起的，但它也与心脏病等全身性疾病有关。预防牙周病需要消除或控制微生物群落。我们的研究考察了一种促进细菌群落发展的独特微生物通讯途径。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。

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.