The proposed research is an extension of previous research pursuing the discovery of a novel antibiotic elaborated by the oral cariogenic bacterium Streptococcus mutans. This potent antibiotic, called mutacin, is a member of the growing class of bacterially synthesized peptide antibiotics called lantibiotics. Lantibiotics are ribosomally synthesized and post-translationally modified peptides containing unusual amino acids called lanthionines, and are produced by, and primarily act on, gram-positive bacteria. Because the mutacin peptide and other lantibiotics are DNA-encoded, changes in their expression and composition can be accomplished by site-directed mutagenesis. For example, genetically-engineered analogues of the nascent mutacin molecule can be modified for an enhanced spectrum of activity against specific pathogens.
The aims of the present research are to define and characterize the genetic and biochemical aspects of mutacin biosynthesis, to document its antimicrobial activities, and to study the factors involved with the regulation of its production. Taking advantage of a rapidly growing repertoire of molecular biological techniques including site-directed and cassette mutagenesis, each component of the mutacin molecule can be manipulated and its role determined. From this information, the production of mutacin may be enhanced by genetic and protein engineering. It is anticipated that, at the end of the next five years, the genetic and biochemical determinants for mutacin will be understood and significant progress made towards the large scale production for possible therapeutic application can be explored. Clearly, the race to find not only a targeted, specific antimicrobial against the etiological agents of dental caries, but also against the emerging group of drug resistant pathogens underpins the importance of this area of scientific pursuit.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Oral Biology and Medicine Subcommittee 1 (OBM)
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Mangan, Dennis F
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University of Alabama Birmingham
Schools of Dentistry
United States
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Ruby, J D; Li, Y; Luo, Y et al. (2003) Genetic diversity of Actinomyces naeslundii genospecies 2 in mother-child pairs. Arch Oral Biol 48:851-5
Li, Yihong; Pan, Yaping; Qi, Fengxia et al. (2003) Identification of Streptococcus sanguinis with a PCR-generated species-specific DNA probe. J Clin Microbiol 41:3481-6
Chen, P; Qi, F X; Novak, J et al. (2001) Effect of amino acid substitutions in conserved residues in the leader peptide on biosynthesis of the lantibiotic mutacin II. FEMS Microbiol Lett 195:139-44
Qi, F; Chen, P; Caufield, P W (2001) The group I strain of Streptococcus mutans, UA140, produces both the lantibiotic mutacin I and a nonlantibiotic bacteriocin, mutacin IV. Appl Environ Microbiol 67:15-21
Li, Y; Caufield, P W; Emanuelsson, I R et al. (2001) Differentiation of Streptococcus mutans and Streptococcus sobrinus via genotypic and phenotypic profiles from three different populations. Oral Microbiol Immunol 16:16-23
Krull, R E; Chen, P; Novak, J et al. (2000) Biochemical structural analysis of the lantibiotic mutacin II. J Biol Chem 275:15845-50
Qi, F; Chen, P; Caufield, P W (2000) Purification and biochemical characterization of mutacin I from the group I strain of Streptococcus mutans, CH43, and genetic analysis of mutacin I biosynthesis genes. Appl Environ Microbiol 66:3221-9
Chen, P; Qi, F; Novak, J et al. (1999) The specific genes for lantibiotic mutacin II biosynthesis in Streptococcus mutans T8 are clustered and can be transferred en bloc. Appl Environ Microbiol 65:1356-60
Qi, F; Chen, P; Caufield, P W (1999) Purification of mutacin III from group III Streptococcus mutans UA787 and genetic analyses of mutacin III biosynthesis genes. Appl Environ Microbiol 65:3880-7
Qi, F; Chen, P; Caufield, P W (1999) Functional analyses of the promoters in the lantibiotic mutacin II biosynthetic locus in Streptococcus mutans. Appl Environ Microbiol 65:652-8

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