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The long-term goal of the proposed research is to determine the role of spirochetes in the etiology of oral infectious diseases and to develop means to prevent or control spirochete infections. There is substantial evidence implicating spirochetes, particularly T denticola, as etiologic agents in periodontal diseases. In acute necrotizing ulcerative gingivitis (ANUG) and some forms of periodontal disease, spirochetes may comprise over 50 percent of the bacterial flora. Previously in this grant, we have helped to expand the number of known cultivated treponemes from 4 to 10 species, and identified an additional 47 currently uncultivable Treponema species. We have developed 16S rRNA based DNA probes that allow identification of cultivable and uncultivable treponemes in clinical samples. Aim 1 of this proposal will determine which spirochetes are associated with a variety of oral infectious diseases, and how treponemes other than T. denticola relate to Socransky's previously described periodontal bacterial complexes. Determining associated pathogens is a requisite first step in any study of infectious disease. Aim 2 will obtain a molecular understanding of msp, a major surface antigen of T. denticola. We will determine the diversity of msp genotypes in individuals and how msp genotypes shift over time in bacterial populations. Preventive measures, such as vaccines, require an understanding of the diversity of epitopes of the major antigens and how expression of antigen diversity varies over time. Aim 3 of this proposal will obtain information on the genome size and degree of host association as reflected by genome size reduction for each of the known cultivable oral treponemes. The final Aim will examine the genomic repertoire of T. maltophilum, a second oral treponeme implicated in oral infections. This genome survey will provide insight into the metabolic and pathogenic capabilities of the organism and will identify targets for vaccines or drug treatment. This research will improve our understanding of a major segment of the oral bacteria and will provide information necessary for the eventual control and prevention of oral infectious diseases such as periodontitis, pericoronitis, ANUG, noma, and Ludwig's angina.

Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.