Molecules Targeting EriC F 1 Increase Streptococcus mutans Fluoride Sensitivity.

This article focuses on the role of fluoride exporters, specifically EriC^F1, in the cariogenic bacterium Streptococcus mutans and explores diphenylurea derivatives as potential enhancers of fluoride's antibacterial efficacy. The study demonstrates that the eriC^F1 gene encodes the primary functional fluoride exporter in S. mutans, with its deletion leading to increased intracellular fluoride accumulation and heightened fluoride sensitivity. Three diphenylurea derivatives were identified through molecular docking and in vitro assays to bind EriC^F1, impair fluoride efflux, and synergistically enhance the antibacterial effect of sodium fluoride (NaF) without increasing membrane permeability. In vivo experiments using a rat caries model showed that compounds 9 and 15 combined with NaF significantly reduced S. mutans cariogenicity with good biocompatibility, suggesting these compounds as promising adjuncts to fluoride in dental caries prevention.