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袋中形成的复杂的多物种群落中茁壮成长。这种生物膜的形成和生长需要群落中物种之间复杂的分子通讯。我们已经证明，牙周病原体A。放线菌共生菌和牙龈卟啉单胞菌产生群体感应信号自诱导物2（AI-2），其可能参与这些生物体之间的种内和种间通信。AI-2调节参与毒力、铁获得和生物膜形成的基因，并且可能是允许这些生物体感知和响应其局部环境的重要机制。我们一般假设A.伴随放线菌和牙龈卟啉单胞菌对AI-2的应答不同，并且这些信号传导系统的结果适合于这些生物体在口腔生物膜中采用的特定存活策略。该提案的长期目标是确定AI-2群体感应是否可以用于控制口腔生物膜的发展。具体的目的是表征AI-2受体和启动细胞对AI-2的反应的早期事件。放线菌共生菌和牙龈卟啉单胞菌，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的输入和细胞内加工来启动细胞应答。对A.将分别研究伴随放线菌和牙龈卟啉单胞菌，以确定它们是否将AI-2的检测与下游基因调控事件偶联。最后，我们将确定高和低亲和力AI-2受体在A.伴放线菌促进该生物体在早期和成熟生物膜上的定殖。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。这些信息可能有助于合理设计新的治疗方法，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%的成年人口中存在，每年用于治疗和预防牙周炎的支出超过140亿美元。牙周炎由生活在牙龈袋中的细菌群落引起，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。我们的研究检查了一个独特的微生物通讯途径，促进细菌群落的发展。我们寻求开发新的潜在药物，通过干扰这种通信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.