OBJECTIVE To explore the effect and potential mechanisms of berberine on formation of biofilms of clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates.

METHODS Totally 95 clinical MRSA isolates were collected from Shanghai Eighth People′s Hospital from Jan. 2023 to Dec. 2023. The 14 biofilm formation-related genes in the strains were detected by polymerase chain reaction (PCR) and multiplex PCR, the minimum inhibitory concentration (MIC) of berberine was determined by microbroth dilution method, the effect of berberine on resistance of biofilm formation was evaluated by crustal violet staining, fluorescence microscope, Congo red agar plate and extracelluar DNA (eDNA). The transcription levels of 9 biofilm formation-related genes were detected by real-time fluorescent quantitative reverse transcription PCR.

RESULTS All of the 95 strains of MRSA carried eno, clfA, clfB and icaA genes, the most widespread gene profile was bbp-eno-ebpS-fnbA-fib-clfA-clfB-icaA-sasG, and 29 strains had the phenotypes with strong capability of biofilm formation. The MIC score of berberine ranged between 64 and 1 024 μg/ml. Berberine with the concentration of 1/2 MIC could inhibit the biofilm formation of MRSA (P < 0.001), and the inhibiting rate of biofilm formation of the MIC ≥512 μg/ml group was higher than that of the MIC≤128 μg/ml group and the MIC 256 μg/ml group (all P < 0.05). The result under the fluorescence microscope showed that the fluorescence intensity of biofilms decreased with the rise of berberine concentration. Berberine could reduce the formation of amyloid fibrils and the release of eDNA, downregulating the transcription levels of icaA, sasG, ebpS, fib, eno, clfA, clfB, bbp and fnbA genes (P < 0.05).

CONCLUSION Berberine may inhibit the biofilm formation of MRSA by downregulating expression levels of related genes, interfering the formation of amyloid fibrils and blocking the release of eDNA, which may provide experimental bases for development of drugs resisting to MRSA biofilms.