Dental caries and various forms of periodontal disease are etiologically related to the accumulation of certain types of bacteria on teeth, in the form of dental plaques. An understanding of plaque formation is, therefore, of considerable significance. This application focuses on a primary step in oral microbial colonization, i.e., the role of specific salivary proteins in promoting, or impairing adhesion of prominent oral bacteria to tooth and soft tissue surfaces.
Three aims are proposed.
Aim I is a microbiological and biochemical study aimed at (a) identifying specific salivary proteins which bind to hydroxyapaptite (HA) and selectively mediate adhesion of strains of Streptococcus mutans, S. sanguis, S. mitior, Actinomyces viscosus and A. naeslundii, (b) identifying salivary proteins which may bind to bacterial cells and prevent their adhesion to HA, and (c) identifying salivary proteins which modulate adhesion of bacteria to human buccal epithelial cells.
Aim II is an immunological, biochemical and microbiological study aimed at the systematic identification and quantitation of salivary proteins, and peptides from their degradation, which provide specific binding sites for bacterial adhesion to teeth or which otherwise modulate bacterial adhesion. Poly- and monoclonal antibodies specific for relevant proteins and peptides will be made and used to (a) develop immunoassays to identify and measure moieties present in saliva and dental pellicle, (b) establish relationships between the presence and concentrations of a given salivary protein(s) or peptide(s) and adhesion of an oral microorganism.
Aim III is a biochemical and microbiological study aimed at (a) elucidating the molecular basis of the adhesion modulating properties of proteins identified in Aim I, by sequencing, by study of defined molecular segments obtained by specific proteolysis, and by determining the effect of specific chemical modifications on adhesion modulating activity, (b) investigating the use of synthetic and natural peptide and oligosaccharide analogs to extend structure-activity studies, and (c) determining the effects of modifying HA surfaces using molecular segments from known HA-reactive proteins, and synthetic peptides on microbial adhesion. Results from these multidisciplinary studies are essential for understanding the initial step in the formation of dental plaque, and they should provide a basis for developing new methods for its prevention and control.
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