Mutants of the mutans streptococci and the wild-type strains from which they were derived will be used to characterize the synthesis of soluble and insoluble glucans. The polymers to be analyzed by molecular exclusion chromatography for size and by gas chromatographic separation of methyl derivatives for linkage composition will be those produced by electrophoretically separated glucosyltrans-ferase (GTF) enzymes isolated by affinity chromatography, as well as those found in adherent plaque deposits in situ. We want to learn what correlations exist between in vitro enzymological assays and in vivo virulence determinants, and whether there is a consistent relationship between the polymers associated with virulent plaques and those of adherent but non-cariogenic variants. To pursue further the questions of how the biosynthetic (GTF) enzymes, the degradative dextranases, and the non-enzymatic glucan-binding factors act in concert, what their roles in sorption are, and whether they possess shared functions, we will produce mono-clonal antibodies against these co-purifying, extracellular proteins which bind to Alpha(1-6) linked matrices and will seek their shared immunological determinants. Apatite sorption-defective mutants will be included. Those variants which are characterized functionally in vitro, form adherent deposits in vivo, and do not cause tooth decay in rodent caries models consuming caries-conducive diets will be tested in competition experiments. Such variants of S. sobrinus and S. mutans, along with an adherrent X. salivarius and wild rat isolates of S. ferus, will be assessed for their abilities to preemptively exclude or competitively displace virulent cariogens from the oral cavities of rats. In a final series of experiments, using biochemically-, virulence-, and competition-characterized mutants, we will study the implantation of non-virulent plaque formers on the teeth of adult humans of high caries experience, and children who by virtue of their environments, are at high risk for infection by and implantation of mutans streptococci. In all these experiments our goal is to understand the structure and dynamics of virulent plaque formation and to use mutants which are non-virulent but orally retained to protect hosts against infection, establishment, and proliferation of cariogenic mutans streptococci.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE003758-11
Application #
3218929
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1977-07-01
Project End
1986-12-31
Budget Start
1985-07-01
Budget End
1986-12-31
Support Year
11
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code