Oxygen metabolism and resultant oxidative damage caused by metabolically generated reactive oxygen species (ROS) are key processes affecting the activities of plaque bacteria. The organisms have developed multiple mechanisms to protect themselves against oxidative damage, including superoxide dismutase, peroxidases, sulfhydryl reductases and DNA repair enzymes. The major source of O2 for supragingival plaque is air in the mouth, while that for subgingival plaque is crevicular fluid. Since plaque is a thin biofilm, O2 moves readily into the film to be metabolized, and plaque generally has been found to have residual O2 levels about 10% that of air-saturated water. However, the important O2 is the metabolized portion, which then is the source of ROS. In addition, many oral healthcare products contain hydrogen peroxide, which can be radicalized through Fenton reactions to cause oxidative damage. The objectives of this application are to develop a clearer picture of oxidative damage to plaque bacteria, primarily oral streptococci, and to identify through use of genetic mutants the major protective mechanisms. Part of the project has a very practical aim of devising better ways to control oral infectious diseases with an emphasis on caries and use of peroxides.
The specific aims are: 1. Determine the roles played by NADH-linked oxidases, peroxidases and glutathione reductase in protection of oral streptococci against hydrogen peroxide and other oxidatively damaging agents, 2. Define the roles that superoxide and superoxide dismutase play in oxidative damage and protection against damage, 3. Elucidate the interactions of transition-metal cations, chelators and fluoride in oxidative damage, including interactions with oxygen- metabolizing and protective enzymes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE013683-03
Application #
6523896
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Mangan, Dennis F
Project Start
2000-09-15
Project End
2005-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
3
Fiscal Year
2002
Total Cost
$305,044
Indirect Cost
Name
University of Rochester
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Baker, J L; Lindsay, E L; Faustoferri, R C et al. (2018) Characterization of the Trehalose Utilization Operon in Streptococcus mutans Reveals that the TreR Transcriptional Regulator Is Involved in Stress Response Pathways and Toxin Production. J Bacteriol 200:
Saputo, S; Faustoferri, R C; Quivey Jr, R G (2018) Vitamin D Compounds Are Bactericidal against Streptococcus mutans and Target the Bacitracin-Associated Efflux System. Antimicrob Agents Chemother 62:
Saputo, S; Faustoferri, R C; Quivey Jr, R G (2018) A Drug Repositioning Approach Reveals that Streptococcus mutans Is Susceptible to a Diverse Range of Established Antimicrobials and Nonantibiotics. Antimicrob Agents Chemother 62:
Castillo Pedraza, Midian C; Novais, Tatiana F; Faustoferri, Roberta C et al. (2017) Extracellular DNA and lipoteichoic acids interact with exopolysaccharides in the extracellular matrix of Streptococcus mutans biofilms. Biofouling 33:722-740
Kovacs, C J; Faustoferri, R C; Quivey Jr, R G (2017) RgpF Is Required for Maintenance of Stress Tolerance and Virulence in Streptococcus mutans. J Bacteriol 199:
Baker, J L; Faustoferri, R C; Quivey Jr, R G (2017) Acid-adaptive mechanisms of Streptococcus mutans-the more we know, the more we don't. Mol Oral Microbiol 32:107-117
Solinski, Amy E; Koval, Alexander B; Brzozowski, Richard S et al. (2017) Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus mutans Biofilms. J Am Chem Soc 139:7188-7191
Baker, Jonathon L; Faustoferri, Roberta C; Quivey Jr, Robert G (2016) A Modified Chromogenic Assay for Determination of the Ratio of Free Intracellular NAD+/NADH in Streptococcus mutans. Bio Protoc 6:
Cross, Benjamin; Faustoferri, Roberta C; Quivey Jr, Robert G (2016) What are We Learning and What Can We Learn from the Human Oral Microbiome Project? Curr Oral Health Rep 3:56-63
Cross, Benjamin; Garcia, Ariana; Faustoferri, Roberta et al. (2016) PlsX deletion impacts fatty acid synthesis and acid adaptation in Streptococcus mutans. Microbiology 162:662-71

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