A Novel target-specific, salt-resistant antimicrobial peptide against the Cariogenic Pathogen Streptococcus mutans

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DOIResolve DOI: http://doi.org/10.1128/AAC.05175-11
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TypeArticle
Journal titleAntimicrobial Agents and Chemotherapy
ISSN0066-4804
1098-6596
Volume55
Issue11
Pages52055213; # of pages: 9
Subjectfusion; peptide imb 2; histidine; polypeptide antibiotic agent; serine; unclassified drug
AbstractIn 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 μM) 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.
Publication date
PublisherAmerican Society for Microbiology
LanguageEnglish
AffiliationNational Research Council Canada; NRC Institute for Marine Biosciences
Peer reviewedYes
NRC number54057
NPARC number21268311
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Record identifierfc7cd937-2333-4027-895c-58a5e6c3ad90
Record created2013-06-19
Record modified2016-06-01
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