Anti-cariogenic activity of mutanocyclin, a secondary metabolite of Streptococcus mutans, in mono- and multispecies biofilms

ABSTRACT Streptococcus mutans (S. mutans), a principal cariogenic pathogen responsible for dental caries, alters the oral biofilm ecology through the production of various metabolites. One such metabolite, mutanocyclin (MUC), a recently identified secondary metabolite, may have implications for both caries development and oral microbiome interactions. This study aimed to investigate the properties of MUC and its effects on S. mutans, as well as other oral commensal streptococci in mono- and multispecies biofilms. Our findings revealed that MUC significantly inhibited S. mutans planktonic growth, biofilm formation, lactic acid production, water-insoluble glucan synthesis, and extracellular polysaccharide production. In contrast, at lower concentrations, MUC stimulated the growth of Streptococcus gordonii (S. gordonii) and Streptococcus sanguinis (S. sanguinis). Additionally, MUC reduced the abundance of S. mutans and enhanced the antagonistic activity of S. gordonii and S. sanguinis against S. mutans in multispecies biofilms by upregulating the expression of the H2O2-related gene spxB and stimulating H2O2 production. These results suggest that MUC has potential for anti-cariogenic activity against S. mutans and for modulating oral microbial communities within the cariogenic microenvironment, providing new therapeutic strategies for preventing dental caries.IMPORTANCEDental caries is a major global health concern, affecting millions and contributing to reduced quality of life and economic burdens. Our study investigated the properties of mutanocyclin (MUC), a recently discovered secondary metabolite produced by S. mutans. Our work sheds light on the role of MUC in modulating microbial communities in the oral cavity. We demonstrated that MUC influences the formation and cariogenicity of S. mutans biofilms and its interactions with other beneficial oral bacteria. This research enhances our understanding of newly discovered secondary metabolites of S. mutans and offers a potential novel strategy for managing the microbial imbalances that lead to caries.