Sodium houttuyfonate inhibits the cariogenic virulence of Streptococcus mutans through the downregulation of VicRK two components pathway.

Background: Caries is one of the most common diseases worldwide, and Streptococcus mutans is considered to be the primary cariogenic pathogen of dental caries. Sodium houttuyfonate (SH) has showed potential antibacterial effects, however, its actions and mechanisms on S. mutans and cariogenicity remain unclear and need further study.

Materials and methods: we investigated the effects of SH on the cariogenic ability of S. mutans, including growth, biofilm formation, exopolysaccharides (EPS) and acid productions. RNA-Seq and mutants' validation were also performed to explore the mechanisms of SH on S. mutans. The dental caries rat model was finally employed to evaluate the anti-caries capabilities of SH.

Results: The MIC of SH against S. mutans was 64 μg/mL. SH inhibited biofilm formation and cariogenic virulence of S. mutans, including EPS and acid productions, in a dose-dependent manner. RNA-seq analysis indicated that SH significantly downregulated the VicRK pathway, a key pathway regulating biofilm formation and EPS generation. The ΔvicK, ASvicR, ΔgtfB and ΔgtfBC mutants were more sensitive to SH, while VicK and VicR overexpression strains OEvicK and OEvicR were more resistant to SH than WT strains, indicating that SH downregulated the VicRK pathway to inhibit the cariogenicity of S. mutans. SH also significantly inhibited the development of dental caries in rats without systematic toxicities. The expressions of S. mutans VicK, VicR, GtfC and GtfD genes from rat plaques were downregulated by SH.

Conclusion: This study suggested SH inhibited the cariogenic virulence of S. mutans through the downregulation of VicRK two components pathway, thereby offering novel insights for clinical caries prevention.