The studies described in this application are to investigate the microbial hydrolysis of urea in the oral cavity and its role in oral health. The elevation in pH resulting from this activity could have beneficial results in surface dental plaque by reducing cariogenic activity of acid producing organisms, whereas in supra-and subgingival plaque ureolysis could have detrimental effects related to increases in calculus and periodontal disease. The experiments proposed here will address both aspects of ureolysis, the first by investigating the regulation of urease expression in Streptococcus salivarius and construction of recombinant urease-producing oral streptococci to test for implantation as biological control agents for caries reduction. In addition the Principal Investigator proposes to analyze the structure and regulation of a recently cloned urease gene locus from Actinomyces naeslundii. Finally, urease-negative mutants of A. naeslundii, constructed by insertional inactivation, will be tested for changes in virulence in an animal model.
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