Effects of a derivative of reutericin 6 and gassericin A on the biofilm of Streptococcus mutans in vitro and caries prevention in vivo.

It is known that Streptococcus mutans (S. mutans) is the leading cariogenic pathogen. Recently, an increasing number of antimicrobial peptides (AMPs) have been brought into consideration as anti-caries agents. Here, we designed and synthesized an AMP derived from reutericin 6 and/or gassericin A, named LN-7, and explored its effect on biofilm of S. mutans UA159 in vitro and development of dental caries in vivo. Antibacterial assays showed that LN-7 was more active against S. mutans (3.2 μM) than many peptide-based agents, capable of killing other types of Streptococci in oral cavity. In addition, LN-7 presented fast killing kinetics, with more than 97% S. mutans killed within 5 min. The mechanism of the antimicrobial activity mainly lies on the disruption of bacterial membrane. Effects of LN-7 on the biofilm formation and the viability of preformed biofilm were quantified by crystal violet staining, which showed that LN-7 could effectively inhibit the biofilm accumulation of S. mutans. Moreover, the biofilm of S. mutans treated with LN-7 displayed notable changes in bacterial viability and morphology, observed by confocal laser scanning microscopy and scanning electron microscopy. In addition, topical oral treatment with LN-7 could suppress the development of dental caries in vivo, reducing the occurrence of severe dental lesion in a rodent model. These results reveal a new peptide-based agent as a topical treatment for dental caries, opening the door to clinical studies to explore its potential for caries prevention.