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

[Abstract] 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.