Harnessing the Regulatory Effects of Streptococcus mutans Two-Component Signal Transduction Systems for Therapeutic Interventions Against Dental Caries.

Streptococcus mutans is considered the main pathogen causing dental caries and has a strong ability to establish biofilms and respond to environmental stimuli, which are essential for its survival and cariogenicity. Fourteen two-component signal transduction systems (TCSs) in S. mutans have been reported to regulate a broad range of physiological processes such as bacterial biofilm formation, acid resistance, competence development, and toxic oxygen metabolite resistance. These systems collectively contribute to the cariogenicity of S. mutans by coordinating adaptive responses to environmental challenges. Among them, the VicRK system has been one of the most extensively studied, with epidemiological evidence linking vicK mutations to increased caries risk in children. Other TCSs, such as ComDE, LiaRS, CiaRH, and the orphan response regulator GcrR, also contribute to cariogenicity regulation. The present review summarizes the regulatory roles of TCSs in virulence traits of S. mutans, with an emphasis on those involved in biofilm formation, which highlights their potential as therapeutic targets to prevent dental caries through biofilm inhibition.