Berberine chloride hydrate impairs Streptococcus mutans biofilm formation via inhibiting sortase A activity

Dental caries is a biofilm-associated chronic progressive disease, results from the dissolution of mineralized tooth tissue by acidic generated from bacterial sugar fermentation. S. mutans, a prominent pathogen of dental caries, is acknowledged for its role in cariogenic biofilm formation, utilizing Sortase A (SrtA) to catalyse surface proteins, thus promoting biofilm formation. In our previous studies, the inhibitory effect of the berberine chloride hydrate (BH) on S. mutans biofilms was confirmed. Here, we further investigate the influence of BH on S. mutans biofilm-induced bovine enamel caries model and explore the effect of BH on S. mutans SrtA activity. We found that BH inhibited S. mutans biofilm formation in bovine enamel model, leading to a reduction in demineralization. Furthermore, we identified and characterized SrtA, which might catalyze SpaP of S. mutans to form fibrillar amyloid aggregates. Our findings showed that BH inhibited SrtA activity by binding to essential amino acid residues LEU-111, MET-123, and ARG-213. BH inhibited amyloid fibers formation by downregulating the expression of srtA gene, thus disrupting S. mutans biofilm formation. Taken together, our study provides new insight into the mechanism of antibiofilm activity of BH and reveals great potential for anticaries clinical applications.