Molecular Basis of Oral Microbial Adhesion

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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.