Xia Shuai, Ma Liyan, Wang Guoxing, Yang Jie, Zhang Meiying, Wang Xuechen, Su Jianrong, Xie Miaorong
Department of Emergency and Critical Care Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
Infect Drug Resist. 2022 Apr 19;15:1933-1944. doi: 10.2147/IDR.S357077. eCollection 2022.
To investigate the antimicrobial activity of berberine and the mechanism by which it combats methicillin-resistant (MRSA) strains isolated from patients with bloodstream infections.
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.
Our data showed berberine was effective against MRSA at MIC values varying from 256 to 64 mgL for different MLST types. Berberine alone, and when combined with clindamycin and rifampicin separately, displayed excellent antibacterial activity which reduced the bacterial counts by 2lgCFUmL 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.
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.
研究小檗碱的抗菌活性及其对抗从血流感染患者中分离出的耐甲氧西林金黄色葡萄球菌(MRSA)菌株的作用机制。
收集15株临床MRSA分离株,并检测其多位点序列类型(MLST)。测定小檗碱单独以及分别与克林霉素和利福平联合使用时的最低抑菌浓度(MIC)和联合抗菌活性。此外,选择两株MRSA菌株(ST239和ST5)进行时间杀菌试验和生物膜形成试验。通过共聚焦激光扫描显微镜(CLSM)和电子显微镜测量细胞壁改变和细胞膜完整性,以评估对细胞形态的影响。
我们的数据显示,对于不同的MLST类型,小檗碱对MRSA有效,MIC值在256至64mgL之间。小檗碱单独以及分别与克林霉素和利福平联合使用时,均表现出优异的抗菌活性,与对照菌株相比,在24小时内可使细菌数量减少2lgCFUmL,并显著减弱生物膜形成。此外,细菌细胞学分析表明,随着浓度增加,小檗碱破坏了细胞壁结构、膜完整性,并进一步改变了细胞形态。
在我们的研究中,小檗碱具有优异的抗MRSA活性,分别与克林霉素和利福霉素联合使用时具有协同抗菌特性,其作用机制涉及细胞壁和细胞膜的破坏。