Pleurocidin congeners demonstrate activity against Streptococcus and low toxicity on gingival fibroblasts

• Several pleurocidin congeners had the antimicrobial effect against Streptococcus mutans, Streptococcus sanguinis and Streptococcus sobrinus.
• Toxicity studies indicated that several congener peptides had little effect on human gingival fibroblasts (HGFs) with 5 min of in vitro treatment.
• Among pleurocidin congeners, pm11 appear to be the best candidates because they were the most potent molecules and lacked significant cytotoxicity.
• The results suggested that peptides with strong activity against S. mutans could be designed by altering native peptides.

ObjectivesFish epidermal antimicrobial peptides, such as pleurocidin, are cathelicidins with broad-spectrum antimicrobial activity against gram negative and gram-positive bacteria, as well as fungi. In the current study, we attempted to optimize peptide bioactivity by sequence modification and assess the antimicrobial activities.MethodsFifteen pleurocidin analogues were designed, and the efficacy of pleurocidin congeners against common cariogenic microorganisms was tested; furthermore, we performed a preliminary study of the antimicrobial mechanism. We assayed the minimal inhibitory concentration (MIC), minimal bactericide concentration (MBC) and bactericidal kinetics to determine the cell killing activity. Scanning electron microscopy (SEM) was used to observe the bacterial membrane after treatment with congeners’ peptides. Human gingival fibroblasts (HGFs) were also used in toxicity studies.ResultsThe MIC and MBC results indicated that peptide congeners had different antimicrobial activities against the tested oral strains. Toxicity studies indicated that several congener peptides had little effect on human gingival fibroblasts (HGFs) with 5 min of in vitro treatment.ConclusionOur findings suggested that several pleurocidin congeners had the antimicrobial effect against Streptococcus mutans, Streptococcus sanguinis and Streptococcus sobrinus.