Streptococcus mutans is the major etiologic agent responsible for Dental caries, the most prevalent disease in the 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. Thus, mutacin production by S. mutans may play a double role: it provides the producing strain with a competitive edge in gaining dominance in the Dental plaque, leading to Dental caries. On the other hand, 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 biogenesis and regulation with the following approaches:
Aim 1, to characterize the trans-acting factors for mutacin gene regulation.
Aim 2, to characterize the cis-acting factors that regulate mutacin gene expression.
Aim 3, to determine the structure/function of the mutacin molecule and improve the properties of mutacins by genetic engineering.
Aim 4, to enhance mutacin biosynthesis and improve fermentation conditions. The proposed research will have a significant impact on two fronts. The first is the alarming surge in resistance to the existing battery of antibiotics by emerging and existing pathogens, and the increasing threat of bioterrorist attack using genetically engineered 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 for mutacin production in S. mutans. This knowledge will help design effective control measures to curb 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 #
1R01DE014757-01A1
Application #
6623730
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
2003-03-03
Budget End
2003-11-30
Support Year
1
Fiscal Year
2003
Total Cost
$317,531
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
Merritt, J; Qi, F (2012) The mutacins of Streptococcus mutans: regulation and ecology. Mol Oral Microbiol 27:57-69
Hung, David C I; Downey, Jennifer S; Kreth, Jens et al. (2012) Oligomerization of the response regulator ComE from Streptococcus mutans is affected by phosphorylation. J Bacteriol 194:1127-35
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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