OBJECTIVE: To construct antimicrobial peptides with potent antimicrobial activity, low cytotoxicity and efficient killing rate of Streptococcus mutans for prevention and treatment of dental caries.METHODS: We exploited the existing design strategies to modify reutericin 6 or gassericin A produced by Lactobacillus species in the oral cavity based on their cationicity, amphipathicity and á-helical structure. We examined their antimicrobial activities using bacterial susceptibility assay, their cytotoxicity through cytotoxicity assay and their killing rate of Streptococcus mutans with time-kill assay. We further evaluated the candidate derivatives for their killing rate against Streptococcus mutans, their antimicrobial activity against different oral pathogens and the development of drug resistance.RESULTS: We constructed 6 AT-1 derivatives, among which AT-7 showed an MIC of 3.3 ìmol/L against Streptococcus mutans, Porphyromonas gingivalis and Actinomyces viscosus with a killing rate of 88.7% against Streptococcus mutans within 5 min. We did not obtain de novo strains of Streptococcus mutans resistant to AT- 7 after induction for 10 passages.CONCLUSIONS: Hydrophobicity and imperfect amphipathic structure are two key parameters that define the antimicrobial potency of the antimicrobial peptides. The imperfectly amphipathic peptide AT-7 shows the potential for clinical application in dental caries treatment.
Anti-Infective Agents Dental Caries