A New Small Molecule Specifically Inhibits the Cariogenic Bacterium Streptococcus mutans in Multispecies Biofilms

Abstract

ABSTRACTStreptococcus mutansis a major cariogenic bacterium. It has adapted to the biofilm lifestyle, which is essential for pathogenesis of dental caries. We aimed to identify small molecules that can inhibit cariogenicS. mutansand to discover lead structures that could give rise to therapeutics for dental caries. In this study, we screened a focused small-molecule library of 506 compounds. Eight small molecules which inhibitedS. mutansat a concentration of 4 μM or less but did not affect cell growth or biofilm formation of commensal bacteria, represented byStreptococcus sanguinisandStreptococcus gordonii, in monospecies biofilms were identified. The active compounds share similar structural properties, which are characterized by a 2-aminoimidazole (2-AI) or 2-aminobenzimidazole (2-ABI) subunit. In multispecies biofilm models, the most active compound also inhibited cell survival and biofilm formation ofS. mutansbut did not affect commensal streptococci. This inhibitor downregulated the expression of six biofilm-associated genes,ftf,pac,relA,comDE,gbpB, andgtfB, in planktonicS. mutanscells, while it downregulated the expression of onlyftf,pac, andrelAin the biofilm cells ofS. mutans. The most potent compound also inhibited production of two key adhesins ofS. mutans, antigen I/II and glucosyltransferase (GTF). However, the compound did not alter the expression of the corresponding genes in bothS. sanguinisandS. gordonii, indicating that it possesses a selective inhibitory activity againstS. mutans.