The overall goal of this research is to study the various virulence components of mutans streptococci at the molecular level. Among the more important factors in the caries process are those components involved with sucrose metabolism; i.e., those enzymes and proteins which bind and utilize sugars for energy production and result in the formation of extracellular polymers found in dental plaque. A further understanding of the involvement of these factors in caries can best be achieved by analyzing the individual components at the molecular level.
The specific aims of this proposal are to: 1. Determine the nucleotide and deduced amino acid sequence of glucosyltransferase (both soluble and insoluble forms), glucan binding proteins, and fructosyltransferase genes obtained from S. mutans and S. sobrinus; 2. Study structure- function relationships of these proteins and identify the roles of local domains and how they are involved in enzyme activity, ligand binding, and overall function; 3. Assess the relatedness, chromosome organization and evolution of these genes and gene products with those from other serotypes of mutans streptococci; 4. Utilize site directed mutagenesis and protein engineering techniques to further understand structure-function relationships of individual proteins and design new proteins which might represent improved candidates for a caries vaccine. The results from this study should provide important information for the understanding of the genetic regulation of these factors as well as a characterization of each component at the molecular level and how they interact with one another. The availability of this information should also allow further strategies to be devised to understand the interaction of various components involved in sucrose metabolism and eventually the control of caries.
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