In vitro Antimicrobial Activity and the Mechanism of Berberine Against Methicillin-Resistant Staphylococcus aureus Isolated from Bloodstream Infection Patients

Purpose: To investigate the antimicrobial activity of berberine and the mechanism by which it combats methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from patients with bloodstream infections. Methods: Fifteen clinical MRSA isolates were collected, and their Multi-locus Sequence Types (MLST) were examined. The minimum inhibitory concentration (MIC) and combined antibacterial activity of berberine alone, and when combined with clindamycin and rifampicin separately, were determined. Additionally, two MRSA strains (ST239 and ST5) were selected to perform the time-killing assay and biofilm formation test. Cell wall alterations and cell membrane integrity were measured by confocal laser scanning microscopy (CLSM) and electron microscopy to assess the influence on cell morphology. Results: Our data showed berberine was effective against MRSA at MIC values varying from 256 to 64 mg*L-1 for different MLST types. Berberine alone, and when combined with clindamycin and rifampicin separately, displayed excellent antibacterial activity which reduced the bacterial counts by 21gCFU*mL within 24h and significantly weakened biofilm formation compared with control strain. Additionally, bacterial cytological profiling indicates that berberine destroyed the structure of the cell walls, membrane integrity and further changed the cell morphology with concentration increased. Conclusion: In our study, berberine has excellent anti-MRSA activities and has synergistic antibacterial property when combined with clindamycin and rifamycin separately, and the mechanism of activities involves the destruction of cell wall and membrane.