Streptococcus mutans is the major etiologic agent responsible for Dental caries, the most prevalent disease in developed and developing countries. Most clinical isolates of S. mutans produce antimicrobial peptides called mutacins. Mutacins are active against a wide spectrum of Gram-positive bacteria, including pathogens and oral commensals. Production of mutacin is under the control of the same regulatory networks involved with stress response, quorum sensing, competence development and biofilm formation. Thus the production of mutacin may play a double role: it may give the producer strain a competitive edge in gaining dominance in the Dental plaque, leading to Dental caries, at the same time, it may protect the human host from Gram-positive bacterial infections. The proposed research Aims to study the genetic, biochemical and biological aspects of mutacin production with the following approaches:
Specific Aim 1, to elucidate the mechanism of regulation for mutacin production.
Specific Aim 2, to develop mutacin into a future antimicrobial drug. The proposed research will have a significant impact on two fronts. The first front is the alarming surge in resistance to the existing battery of antibiotics among emerging and existing bacterial pathogens, and the increasing threat of bio-terrorist attack using genetically engineered anthrax pathogens resistant to all existing antibiotics. These threats underpin the importance and urgency of finding unconventional antibiotics, to which resistance has not been developed. The second front is understanding the mechanism of gene regulation in S. mutans during stress response and biofilm formation. This knowledge will help design effective measures to control the growth and virulence of S. mutans in the Dental plaque.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
3R01DE014757-01A1S1
Application #
6753428
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Mangan, Dennis F
Project Start
2003-03-03
Project End
2007-11-30
Budget Start
2003-06-01
Budget End
2003-11-30
Support Year
1
Fiscal Year
2003
Total Cost
$34,727
Indirect Cost
Name
University of California Los Angeles
Department
Dentistry
Type
Schools of Dentistry
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Hung, David C I; Downey, Jennifer S; Ayala, Eduardo A et al. (2011) Characterization of DNA binding sites of the ComE response regulator from Streptococcus mutans. J Bacteriol 193:3642-52
Wu, Chenggang; Ayala, Eduardo A; Downey, Jennifer S et al. (2010) Regulation of ciaXRH operon expression and identification of the CiaR regulon in Streptococcus mutans. J Bacteriol 192:4669-79
Wu, Chenggang; Cichewicz, Robert; Li, Yihong et al. (2010) Genomic island TnSmu2 of Streptococcus mutans harbors a nonribosomal peptide synthetase-polyketide synthase gene cluster responsible for the biosynthesis of pigments involved in oxygen and H2O2 tolerance. Appl Environ Microbiol 76:5815-26
Okinaga, T; Xie, Z; Niu, G et al. (2010) Examination of the hdrRM regulon yields insight into the competence system of Streptococcus mutans. Mol Oral Microbiol 25:165-77
Niu, Guoqing; Okinaga, Toshinori; Qi, Fengxia et al. (2010) The Streptococcus mutans IrvR repressor is a CI-like regulator that functions through autocleavage and Clp-dependent proteolysis. J Bacteriol 192:1586-95
Xie, Zhoujie; Okinaga, Toshinori; Niu, Guoqing et al. (2010) Identification of a novel bacteriocin regulatory system in Streptococcus mutans. Mol Microbiol 78:1431-47
Okinaga, Toshinori; Niu, Guoqing; Xie, Zhoujie et al. (2010) The hdrRM operon of Streptococcus mutans encodes a novel regulatory system for coordinated competence development and bacteriocin production. J Bacteriol 192:1844-52
Kreth, Jens; Merritt, Justin; Qi, Fengxia (2009) Bacterial and host interactions of oral streptococci. DNA Cell Biol 28:397-403

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