| Title: | Targeted killing of Streptococcus mutans by a pheromone-guided 'smart' antimicrobial peptide |
| Author(s): | Eckert R; He J; Yarbrough DK; Qi F; Anderson MH; Shi W; |
| Address: | "Department of Microbiology, Immunology, and Molecular Genetics,1 School of Dentistry, University of California, Los Angeles, California 90095, USA" |
| Journal Title: | Antimicrob Agents Chemother |
| ISSN/ISBN: | 0066-4804 (Print) 1098-6596 (Electronic) 0066-4804 (Linking) |
| 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 (or selectively) 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 multispecies microbial community (dental plaque). In particular, we explored the possibility of utilizing a pheromone produced by S. mutans, namely, the 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 multispecies biofilms without affecting closely related noncariogenic 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" |
| Keywords: | "Anti-Bacterial Agents/chemical synthesis/*pharmacology Biofilms/drug effects/growth & development Dental Caries/microbiology Fluorescent Dyes Humans Kinetics Microbial Sensitivity Tests Microscopy, Fluorescence Peptides/chemical synthesis/*pharmacology Ph;" |
| Notes: | "MedlineEckert, Randal He, Jian Yarbrough, Daniel K Qi, Fengxia Anderson, Maxwell H Shi, Wenyuan eng R01 DE014757/DE/NIDCR NIH HHS/ 2-T32-A1-07323/PHS HHS/ R41 MD001831/MD/NIMHD NIH HHS/ R41-MD01831/MD/NIMHD NIH HHS/ R01-DE014757/DE/NIDCR NIH HHS/ Research Support, N.I.H., Extramural 2006/10/25 Antimicrob Agents Chemother. 2006 Nov; 50(11):3651-7. doi: 10.1128/AAC.00622-06" |
