Regulation of water-soluble glucan synthesis by the Streptococcus mutans dexA gene effects biofilm aggregation and cariogenic pathogenicity

The cariogenic pathogen Streptococcus mutans effectively utilizes dietary sucrose for the synthesis of exopolysaccharides (EPS), which act as a scaffold for its biofilm and thus contribute to its cariogenic pathogenicity. Dextranase (Dex), which is a type of glucanase, participates in the degradation of water-soluble glucan (WSG); however, the structural features of the EPS regulated by the dexA gene have received limited attention. Our recent studies reported novel protocols to fractionate and analyzed the structural characteristics of glucans from S mutons biofilms. In this study, we identify the role of the S mutans dexA gene in dextran-dependent aggregation in biofilm formation. Our results show that deletion of dexA (SmudexA) results in increased transcription of EPS synthesis-related genes, including gtfB, gtfD, and ftf. Interestingly, we reveal that inactivating the dexA gene may lead to elevated WSG synthesis in S mutans, which results in dysregulated cariogenicity in vivo. Furthermore, structural analysis provides new insights regarding the lack of mannose monosaccharides, especially in the WSG synthesis of the SmudexA mutants. The biofilm phenotypes that are associated with the reduced glucose monosaccharide composition in both WSG and water-insoluble glucan shift the dental biofilm to reduce the cariogenic incidence of the SmudexA mutants. Taken together, these data reveal that EPS synthesis finetuning by the dexA gene results in a densely packed EPS matrix that may impede the glucose metabolism of WSG, thereby leading to the lack of an energy source for the bacteria. These results highlight dexA targeting as a potentially effective tool in dental caries management.