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Antimicrob. Agents Chemother. doi:10.1128/AAC.00622-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Targeted killing of Streptococcus mutans by a pheromone guided "smart" antimicrobial peptide

Department of Microbiology, Immunology, and Molecular Genetics and School of Dentistry, University of California, Los Angeles, CA 90095, U.S.A; C3 Jian, Incorporated, Sequim, WA98382

^* To whom correspondence should be addressed. Email: wenyuan{at}ucla.edu.

	Abstract

Within the repertoire of antibiotics available to a prescribing clinician, the majority affect a broad range of microorganisms, including the normal flora. The ecological disruption resulting from antibiotic treatment frequently results in secondary infections or other negative clinical consequences. To address this problem, our laboratory has recently developed a new class of pathogen-selective molecules, called specifically targeted antimicrobial peptides (STAMPs), based on the fusion of a species-specific targeting peptide domain with a wide spectrum antimicrobial peptide domain. In the current study, we focused on achieving targeted killing of Streptococcus mutans, a cavity-causing bacterium that resides in a multi-species microbial community (dental plaque). In particular, we explored the possibility of utilizing a pheromone produced by S. mutans, competence stimulating peptide (CSP), as a STAMP targeting domain to mediate S. mutans-specific delivery of an antimicrobial peptide domain. We discovered that STAMPs constructed with peptides derived from CSP were potent against S. mutans grown in liquid or biofilm states, but did not affect other oral streptococci tested. Further studies showed that an 8 amino acid region within the CSP sequence is sufficient for targeted delivery of the antimicrobial peptide domain to S. mutans. The STAMPs presented here are capable of eliminating S. mutans from multi-species biofilms, without affecting closely-related non-cariogenic oral streptococci, indicating the potential of these molecules to be developed into "probiotic" antibiotics which could selectively eliminate pathogens while preserving the protective benefits of a healthy normal flora.

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