Molecular Basis of Oral Microbial Adhesion

描述：牙周病是由于宿主和口腔微生物群的相互作用而导致的支持牙齿的组织的复杂的慢性炎症状态。微生物在疾病的初始阶段发挥作用，是激活宿主炎症反应的触发因素。这涉及宿主和细菌之间一系列复杂的相互作用，然而到目前为止，细菌和介导这些相互作用的宿主成分仍然不清楚。启动感染的一个基本步骤涉及病原体或其产物与宿主细胞的粘连。细菌细胞表面蛋白是第一个与宿主环境接触的蛋白，也最有可能是这一过程的媒介。尽管人们对好氧外膜和细胞表面蛋白了解很多，但对厌氧细菌的了解却很少。牙龈卟啉单胞菌、福赛坦纳氏菌和中间普雷沃特氏菌等厌氧菌与牙周病的发生有关。我们建议调查口腔厌氧细菌的细胞表面蛋白在宿主微生物建立的第一步中的作用：口腔定植。具体地说，首先我们将对沪指进行定性。中间体17纤维连接蛋白结合蛋白，AdpA。其次，结合细胞标记和蛋白质组学方法，我们将鉴定其他能够与宿主成分结合的细胞表面蛋白：例如唾液蛋白、基膜蛋白和宿主细胞。这些蛋白质还将被进一步鉴定，以确定它们在介导Prev附着中的作用。用于承载组件的InterMedia。这个应用程序的长期目标是识别Prev。这将进一步了解细菌致病机制的介体，并最终导致确定潜在的抗牙周炎疫苗候选。

DESCRIPTION: Periodontal diseases are complex chronic inflammatory conditions of tissues supporting the teeth resulting from the interaction between host and oral microflora. Microorganisms play a role in the initial stages of the diseases serving as a trigger for activation of the host inflammatory response. This involves complex set of interactions between the host and the bacteria, however to date the bacterial and the host components mediating these interactions remain not well understood. An essential step in initiating the infection involves adherence to host cells by the pathogens or their products. Bacterial cell surface proteins are the first to come in contact with the host environment and are most likely mediators of this process. Although much is known about aerobic outer membrane and cell surface proteins this knowledge is sparse regarding anaerobic bacteria. Anaerobes such as Porphyromonas gingivalis, Tannerella forsythensis, and Prevotella intermedia are implicated in development of periodontal diseases. We propose to investigate the role of cell surface proteins of the oral anaerobic bacteria in the first step of establishment of the microorganisms in the host: colonization of the oral cavity. Specifically, first we will characterize the Prev. intermedia 17 fibronectin-binding protein, AdpA. Second, using combination of cell labeling and proteomic approaches we will identify other cell surface proteins capable of binding to host components: e.g. salivary proteins, basal membrane proteins, and host cells. These proteins also will be further characterized to determine their role in mediating the attachment of Prev. intermedia to host components. The long-term objective of this application is to identify Prev. intermedia adhesins, which will further knowledge of mediators of the pathogenesis of the bacterium and ultimately lead to identification of potential anti-periodontitis vaccine candidates.