The inhibitory effect of berberine chloride hydrate on Streptococcus mutans biofilm formation at different pH values

Streptococcus mutans (S. mutans) is one of the major cariogenic bacteria of dental caries owing to its ability to adhere to tooth surfaces and biofilm formation. Berberine chloride hydrate (BH), a quaternary ammonium salt alkaloid, has diverse pharmacological efforts against Microorganisms. However, the effect of BH on S. mutans biofilm has not been reported. Considering that berberine is a quaternary ammonium salt alkaloid, which needs to adapt to a large variation in pH values and the acid resistance of S. mutans, we employed three groups including pH 5 (acidic), pH 8 (alkaline), and unprocessed group (neutral) to examine the antibiofilm activities of BH against S. mutans during different pH values. In this study, we found BH effectively suppresses S. mutans biofilm formation as well as its cariogenic virulence including acid production and EPS synthesis significantly, and the inhibitory effort was reduced under acidic condition whereas elevated under alkaline condition. In addition, we preliminarily explored the influence of pH values on the structural stability and biosafety of BHas well as the underlying mechanism of inhibition of S. mutans biofilm formation with BH. Our study showed BH could maintain a good structural stability and low toxicity to erythrocytes at different pH values. And BH could downregulate the expression of srtA, spaP, and gbpC, which play critical roles in the adhesion process, promoting Bacterial colonization and biofilm formation. Furthermore, comX and ldh expression levels were downregulated in BH-treated group, which might explain its inhibitory effect on acid production.IMPORTANCEDental caries is a common chronic detrimental disease, which could cause a series of oral problem including oral pain, difficulties in eating, and so on. Recently, many Natural Products have been considered as fundamental sources of therapeutic drugs to prevent caries. Berberine as a plant extract showed good antibiofilm abilities against microorganism. Our study focuses on its antibiofilm abilities against S. mutans, which was defined as major cariogenic bacterium and explored the role of pH values and possible underlying mechanisms in the inhibitory effect of BH on S. mutans biofilm formation. This study demonstrated a promising prospect for BH as an adjuvant drug in the prevention and management of dental caries.

Streptococcus mutans; berberine chloride hydrate; biofilm; pH; virulence.