Oral treponemes have been implicated in acute necrotizing ulcerative gingivitis, in chronic adult periodontitis, and in rapidly progressive periodontitis. However, the mode of virulence remains unclear. A first step in treponemal virulence is believed to be adhesion to host cells. Recent progress has been made in identifying and characterizing a 64 kDa monomeric subunit of a high molecular weight oligomeric surface protein (O-protein) of Treponema denticola, that apparently interacts with host cells. Recent findings suggest that the O-protein is a complex protein aggregate with a molecular weight in excess of 1000 kDa. The overall goal of this application is to study this protein as a mechanism for T. denticola adherence to host cells. The objectives are first, to study the structural organization of the O-protein; second, to complete the amino acid sequence of the 64 kDa subunit; third, to identify the adhesive component(s) of the O-protein via analysis of functional domain(s); and fourth, to extend studies of the interaction of human gingival fibroblasts with human gingival epithelial cells. These objectives are a logical progression of preliminary work, and are intended to provide more evidence that the O-protein is intricately associated with T. denticola-host cell interactions. Methods to be used in the study include bacterial and mammalian cell cultures, protein chemistry, amino acid sequence analysis, immunohistochemistry, light and electron microscopy, affinity chromatography, gene cloning, and nucleotide sequence analysis. Functional studies using both human gingival fibroblasts and human gingival epithelial cell cultures will be combined with biochemical and microbiological techniques to aid in defining the role of the T. denticola O-protein associated with pathogenesis.
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