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

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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.

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Acknowledgements

The work was supported by the Science and Technology Department of Guangdong Province of China (2018B030311047) and the Science and Technology Program of Guangzhou, China (201804010419).

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Correspondence to Wanghong Zhao.

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10266_2020_529_MOESM1_ESM.docx

Fig. S1 Killing kinetics of LN-7 against S. mutans UA159, S. sobrinus ATCC33478 and S. gordonii ATCC10558.  (DOCX 119 kb)

Fig. S2 Bactericidal kinetics of LN-7 tested by optical density assay. (DOCX 231 kb)

Fig. S3 HPLC chromatograms of LN-7 (DOCX 251 kb)

Fig. S4 MS characterization of LN-7 (DOCX 115 kb)

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Liang, J., Liang, D., Liang, Y. et al. Effects of a derivative of reutericin 6 and gassericin A on the biofilm of Streptococcus mutans in vitro and caries prevention in vivo. Odontology 109, 53–66 (2021). https://doi.org/10.1007/s10266-020-00529-5

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