title: A novel target-specific, salt-resistant antimicrobial peptide against the cariogenic pathogen Streptococcus mutans.
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 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.
authors.affiliation: Department of Applied Oral Sciences, Dalhousie University, Halifax, Canada.
authors.forename: Junni
authors.initials: J
authors.lastname: Mai
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Tian
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Gallant
authors.forename: Nadine
authors.initials: N
authors.lastname: Merkley
authors.forename: Zakia
authors.initials: Z
authors.lastname: Biswas
authors.forename: Raymond
authors.initials: R
authors.lastname: Syvitski
authors.forename: Susan E
authors.initials: SE
authors.lastname: Douglas
authors.forename: Junqi
authors.initials: J
authors.lastname: Ling
authors.forename: Yung-Hua
authors.initials: YH
authors.lastname: Li
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D004492:Edetic Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D012965:Sodium Chloride / Q000737:chemistry; D013295:Streptococcus mutans / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides; D012965:Sodium Chloride; D004492:Edetic Acid