OBJECTIVE To evaluate the in vitro inhibitory effect of berberine on Staphylococcus aureus, and to explore its underlying mechanisms of antibacterial activity and biofilm inhibition.

METHODS The inhibitory zone diameter of berberine against S. aureus was determined by the inhibition zone method. The minimum inhibitory concentration （MIC） and minimum bactericidal concentration （MBC） were determined by the broth microdilution method, and the minimum biofilm inhibitory concentration （MBIC） was determined by the crystal violet semi-quantitative staining assay. Bacterial distribution after 48 h of berberine treatment was observed by laser scanning confocal microscopy. Biofilm morphology and thickness changes were characterized by atomic force microscopy. Finally, the interactions between berberine and key biofilm-related proteins, including ClfA, NorA, SigB and IcaA, were analyzed by molecular docking.

RESULTS Berberine exhibited significant in vitro inhibitory activity against S. aureus, with an inhibition zone diameter of (16.24±0.48) mm, an MIC of 0.1 mg/ml, an MBC of 0.2 mg/ml and an MBIC of 0.1 mg/ml. Berberine inhibited the formation of S. aureus biofilms in a concentration-dependent manner and disrupted the structure of mature biofilms. Microscopic observation revealed a reduction in the number of bacteria within the biofilm and a significant decrease in biofilm thickness after berberine intervention. Molecular docking confirmed that berberine could stably bind to ClfA, NorA, SigB and IcaA proteins and form intermolecular interactions.

CONCLUSIONS Berberine demonstrates good in vitro activity against S. aureus. Its mechanism of action may be related to targeting and binding to key proteins such as ClfA, NorA, SigB and IcaA, thereby inhibiting biofilm synthesis.