The group of organisms known as the mutans streptococci possess the ability to metabolize a variety of sugars, resulting in acid and extracellular glucan production, both of which contribute to the development of human dental caries. The overall goals of this study are to understand the genetics of sugar metabolism and further characterize at the molecular level the various factors involved in the virulence of this organism. To achieve this goal this proposal will focus on two main areas of investigation; first, those factors involved in the production and regulation of extracellular proteins which synthesize and associate with glucans; and second, a further definition of the pathways of intracellular sugar metabolism.
The specific aims of this proposal are to: 1 Define in further detail the manner in which extracellular proteins are involved with glucan production and association. 2. Characterize the manner in which extracellular proteins are subjected to regulation. 3. Elucidate the pathways of sugar metabolism encoded in the clustered gene region responsible for glucose, galactose, and multiple sugar metabolism. 4. Identify and characterize the regulatory mechanisms involved in intracellular sugar metabolism. The results from this study should provide important information at the molecular level for the elucidation of the genetics of sugar metabolism in the mutans streptococci. Knowledge of the structure and function of various components involved in sugar metabolism, as well as the mechanisms involved in their control and regulation, should provide meaningful insight into how these organisms are able to function and initiate caries. Such information is essential for the formulation of the strategies to disrupt these mechanisms and the design of rational approaches to control caries.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE008191-06
Application #
3221991
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1987-09-01
Project End
1997-09-29
Budget Start
1992-09-30
Budget End
1993-09-29
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Oklahoma Health Sciences Center
Department
Type
Schools of Dentistry
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
Colby, S M; McLaughlin, R E; Ferretti, J J et al. (1999) Effect of inactivation of gtf genes on adherence of Streptococcus downei. Oral Microbiol Immunol 14:27-32
Ajdic, D; Ferretti, J J (1998) Transcriptional regulation of the Streptococcus mutans gal operon by the GalR repressor. J Bacteriol 180:5727-32
Colby, S M; Russell, R R (1997) Sugar metabolism by mutans streptococci. Soc Appl Bacteriol Symp Ser 26:80S-88S
Ajdic, D; Sutcliffe, I C; Russell, R R et al. (1996) Organization and nucleotide sequence of the Streptococcus mutans galactose operon. Gene 180:137-44
McLaughlin, R E; Ferretti, J J (1996) The multiple-sugar metabolism (msm) gene cluster of Streptococcus mutans is transcribed as a single operon. FEMS Microbiol Lett 140:261-4
Sutcliffe, I C; Russell, R R (1995) Lipoproteins of gram-positive bacteria. J Bacteriol 177:1123-8
Colby, S M; Harrington, D J; Russell, R R (1995) Identification and genetic characterisation of melibiose-negative isolates of Streptococcus mutans. Caries Res 29:407-12
Tao, L; Sutcliffe, I C; Russell, R R et al. (1995) Regulation of the multiple sugar metabolism operon in Streptococcus mutans. Dev Biol Stand 85:343-50
Colby, S M; Whiting, G C; Tao, L et al. (1995) Insertional inactivation of the Streptococcus mutans dexA (dextranase) gene results in altered adherence and dextran catabolism. Microbiology 141 ( Pt 11):2929-36
Colby, S M; Whiting, G C; Russell, R R (1995) Inactivation of the dextranase gene in Streptococcus mutans. Dev Biol Stand 85:377-81

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