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.
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