| Title: | "A novel target-specific, salt-resistant antimicrobial peptide against the cariogenic pathogen Streptococcus mutans" |
| Author(s): | Mai J; Tian XL; Gallant JW; Merkley N; Biswas Z; Syvitski R; Douglas SE; Ling J; Li YH; |
| Address: | "Department of Applied Oral Sciences, Dalhousie University, Halifax, Canada" |
| Journal Title: | Antimicrob Agents Chemother |
| ISSN/ISBN: | 1098-6596 (Electronic) 0066-4804 (Print) 0066-4804 (Linking) |
| Abstract: | "In this study, we constructed and evaluated a target-specific, salt-resistant antimicrobial peptide (AMP) that selectively targeted Streptococcus mutans, a leading cariogenic pathogen. The rationale for creating such a peptide was based on the addition of a targeting domain of S. mutans ComC signaling peptide pheromone (CSP) to a killing domain consisting of a portion of the marine-derived, broad-spectrum AMP pleurocidin to generate a target-specific AMP. Here, we report the results of our assessment of such fusion peptides against S. mutans and two closely related species. The results showed that nearly 95% of S. mutans cells lost viability following exposure to fusion peptide IMB-2 (5.65 muM) for 15 min. In contrast, only 20% of S. sanguinis or S. gordonii cells were killed following the same exposure. Similar results were also observed in dual-species mixed cultures of S. mutans with S. sanguinis or S. gordonii. The peptide-guided killing was further confirmed in S. mutans biofilms and was shown to be dose dependent. An S. mutans mutant defective in the CSP receptor retained 60% survival following exposure to IMB-2, suggesting that the targeted peptide predominantly bound to the CSP receptor to mediate killing in the wild-type strain. Our work confirmed that IMB-2 retained its activity in the presence of physiological or higher salt concentrations. In particular, the fusion peptide showed a synergistic killing effect on S. mutans with a preventive dose of NaF. In addition, IMB-2 was relatively stable in the presence of saliva containing 1 mM EDTA and did not cause any hemolysis. We also found that replacement of serine-14 by histidine improved its activity at lower pH. Because of its effectiveness, salt resistance, and minimal toxicity to host cells, this novel target-specific peptide shows promise for future development as an anticaries agent" |
| Keywords: | Anti-Infective Agents/chemistry/*pharmacology Edetic Acid/chemistry Hydrogen-Ion Concentration Microbial Sensitivity Tests Peptides/chemistry/*pharmacology Sodium Chloride/chemistry Streptococcus mutans/*drug effects; |
| Notes: | "MedlineMai, Junni Tian, Xiao-Lin Gallant, Jeffrey W Merkley, Nadine Biswas, Zakia Syvitski, Raymond Douglas, Susan E Ling, Junqi Li, Yung-Hua eng Canadian Institutes of Health Research/Canada Research Support, Non-U.S. Gov't 2011/08/17 Antimicrob Agents Chemother. 2011 Nov; 55(11):5205-13. doi: 10.1128/AAC.05175-11. Epub 2011 Aug 15" |
