The genesis of dental caries is a complicated process, involving bacterial adhesion to pellicle, accumulation of bacteria, foodstuffs and salivary proteins to form plaque, and finally the production of organic acids by the bacteria. The localized production of acid may result in the localized demineralization of the tooth. Interference in bacterial adhesion, accumulation or acid production may prevent caries formation. The mutans streptococci are the pripiary causative agents of dental caries. These bacteria are acidogenic and aciduric. The mutans streptococci can also utilize sucrose as a source of fermentable carbohydrate and as a substrate for D-glucan synthesis. The D-glucans may be involved in the sucrose-dependent accumulation of streptococci on pellicle. It is a thesis of this proposed research that the streptococcal glucan-binding lectin (GBL) is a virulence coniponent. The lectin may tether streptococci to glucan on pellicle or the lectin may serve to anchor streptococci to streptococci in plaque. We are now in a position to study the structure, function, regulation and role in caries of the GBL of the mutans streptococci.
The specific aims for this research are outlined below. 1) To purify and characterize the GBL from S. sobrinus and other selected oral streptococci. 2) To study the inhibition of the GBL by fluoride and chelating agents, including lactic acid. 3) To study how manganous ion regulates GBL activity in S. sobrinus and other oral streptococci . 4) To determine if sucrose induce-s GBL activity in S. mutans and other oral streptococci. 5) Synthesize glucan and chemically-modified glucan inhibitors of GBL. 6) Clone the GBL gene fron, Streptococcus sobrinus 6715 into the GBL-free Streptococcus mutans GS-5. 7) Study caries induction rats employing S. mutans GS-5 GBL- and S. mutans gbl+'. Determine whether glucan T-10 or its derivatives will inhibit caries induced by sucrose in rats infected with either S. sobrinus 6715 or S. mutans gbl-'. These studies will reveal important new information about the role of the streptococcal GBL in dental caries.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE007199-07
Application #
3220735
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1985-09-01
Project End
1994-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
7
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Louisville
Department
Type
Schools of Medicine
DUNS #
City
Louisville
State
KY
Country
United States
Zip Code
40292
Wang, Q; Singh, S; Taylor, K G et al. (1996) Anti-adhesins of Streptococcus sobrinus. Adv Exp Med Biol 408:249-62
Ma, Y; Lassiter, M O; Banas, J A et al. (1996) Multiple glucan-binding proteins of Streptococcus sobrinus. J Bacteriol 178:1572-7
Doyle, R J; Rosenberg, M (1995) Measurement of microbial adhesion to hydrophobic substrata. Methods Enzymol 253:542-50
Schilling, K M; Doyle, R J (1995) Bacterial adhesion to hydroxylapatite. Methods Enzymol 253:536-42
Wang, J; Singh, S; Taylor, K G et al. (1995) Streptococcal glucan-binding lectins do not recognize methylated alpha-1,6 glucans. Glycoconj J 12:109-12
Ness-Greenstein, R B; Rosenberg, M; Doyle, R J et al. (1995) DNA from Serratia marcescens confers a hydrophobic character in Escherichia coli. FEMS Microbiol Lett 125:71-5
Wu, Q; Wang, Q; Taylor, K G et al. (1995) Subinhibitory concentrations of antibiotics affect cell surface properties of Streptococcus sobrinus. J Bacteriol 177:1399-401
Ciopraga, J; Motas, C; Doyle, R J (1995) Inhibition of saliva-induced oral streptococcal aggregation by blood group glycoproteins. FEMS Immunol Med Microbiol 10:145-9
Galperin, M Y; Lassiter, M; Ma, Y et al. (1995) Chemiluminescent detection of dextran bound to streptococcal glucan-binding lectin. Anal Biochem 225:185-7
Cox, S D; Lassiter, M O; Taylor, K G et al. (1994) Fluoride inhibits the glucan-binding lectin of Streptococcus sobrinus. FEMS Microbiol Lett 123:331-4

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