The proposed work will focus on the physiology and genetics of Streptococcus sanguis, specifically on the arginine deiminase system, with a view to developing implantable strains to moderate the pH drop in dental plaque after sugar challenge and to accelerate the subsequent pH rise. The bases for the proposal are the past successes of others in implanting variant strains of S. sanguis in humans and animals and our isolation of variants of the bacterium nonrepressible for the arginine deiminase system. These variants are able to produce ammonia from arginine while they are producing acids from dietary sugars. The ammonia partly neutralizes the acids and moderates the pH drop in cultures of the variants. The first phases of the work will involve studies of the basic physiology of the arginine deiminase system, including determinations of the range of substrates and inducers, the final products of arginine degradation, the nature of feedback inhibition and of catabolite repression, and the limiting steps in ammonia production. Then, a genetic characterization of the system will include fine-structure mapping of the genes of the system by transformation analysis, cloning of the genes on plasmids and studies of the genetic regulatory elements for the system. The prime objective of the physiological and genetic work will be to construct nonrepressible strains with enhanced capacities to produce ammonia from arginine or from peptides such as sialin. The constructed strains will then be tested for their abilities to compete with other S. sanguis stains and with Streptococcus mutans in in-vitro plaque in continuous culture. Finally, attempts will be made to implant the constructed strains in rats prior to implantation into human plaque. The genetic work will be carried out in conjunction with the Microbial Genetics Facility of the Cariology Center and the implantation studies in conjunction with the Animal Facility of the Center.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Specialized Center (P50)
Project #
5P50DE007003-04
Application #
3940109
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Miguel, J C; Bowen, W H; Pearson, S K (1997) Effects of frequency of exposure to iron-sucrose on the incidence of dental caries in desalivated rats. Caries Res 31:238-43
Vacca-Smith, A M; Venkitaraman, A R; Schilling, K M et al. (1996) Characterization of glucosyltransferase of human saliva adsorbed onto hydroxyapatite surfaces. Caries Res 30:354-60
Venkitaraman, A R; Vacca-Smith, A M; Kopec, L K et al. (1995) Characterization of glucosyltransferaseB, GtfC, and GtfD in solution and on the surface of hydroxyapatite. J Dent Res 74:1695-701
Van Wuyckhuyse, B C; Perinpanayagam, H E; Bevacqua, D et al. (1995) Association of free arginine and lysine concentrations in human parotid saliva with caries experience. J Dent Res 74:686-90
Perinpanayagam, H E; Van Wuyckhuyse, B C; Ji, Z S et al. (1995) Characterization of low-molecular-weight peptides in human parotid saliva. J Dent Res 74:345-50
Zhang, G H; Melvin, J E (1994) Nicotine increases [Ca2+]i in rat sublingual mucous acini by stimulating neurotransmitter release from presynaptic terminals. Proc Soc Exp Biol Med 207:292-301
Bowen, W H; Pearson, S K (1994) Residual effects of fluoride on a severe cariogenic challenge in rats. Caries Res 28:246-50
Adair, S M; Leverett, D H; Shaffer, C L (1994) Interexaminer agreement for readings of dip slide tests for salivary mutans streptococci and lactobacilli. Caries Res 28:123-6
Zhang, G H; Melvin, J E (1994) Intracellular Mg2+ movement during muscarinic stimulation. Mg2+ uptake by the intracellular Ca2+ store in rat sublingual mucous acini. J Biol Chem 269:10352-6
O'Connell, A C; Bowen, W H (1994) Composition and flow rate of saliva and caries development in young rats following administration of lithium. Caries Res 28:342-7

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