School of Diagnostic and Applied Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
School of Chemical Sciences and Food Technology, Faculty of Sciences and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.
Biomed Res Int. 2014;2014:461756. doi: 10.1155/2014/461756. Epub 2014 Mar 24.
Stilbenoids have been considered as an alternative phytotherapeutic treatment against methicillin-resistant Staphylococcus aureus (MRSA) infection. The combined effect of ε-viniferin and johorenol A with the standard antibiotics, vancomycin and linezolid, was assessed against MRSA ATCC 33591 and HUKM clinical isolate. The minimum inhibitory concentration (MIC) value of the individual tested compounds and the fractional inhibitory concentration index (FICI) value of the combined agents were, respectively, determined using microbroth dilution test and microdilution checkerboard (MDC) method. Only synergistic outcome from checkerboard test will be substantiated for its rate of bacterial killing using time-kill assay. The MIC value of ε -viniferin against ATCC 33591 and johorenol A against both strains was 0.05 mg/mL whereas HUKM strain was susceptible to 0.1 mg/mL of ε-viniferin. MDC study showed that only combination between ε-viniferin and vancomycin was synergistic against ATCC 33591 (FICI 0.25) and HUKM (FICI 0.19). All the other combinations (ε-viniferin-linezolid, johorenol A-vancomycin, and johorenol A-linezolid) were either indifferent or additive against both strains. However, despite the FICI value showing synergistic effect for ε-viniferin-vancomycin, TKA analysis displayed antagonistic interaction with bacteriostatic action against both strains. As conclusion, ε-viniferin can be considered as a bacteriostatic stilbenoid as it antagonized the bactericidal activity of vancomycin. These findings therefore disputed previous report that ε-viniferin acted in synergism with vancomycin but revealed that it targets similar site in close proximity to vancomycin's action, possibly at the bacterial membrane protein. Hence, this combination has a huge potential to be further studied and developed as an alternative treatment in combating MRSA in future.
白藜芦醇类化合物被认为是治疗耐甲氧西林金黄色葡萄球菌 (MRSA) 感染的一种替代植物疗法。分别采用微量肉汤稀释法和微量稀释棋盘法测定了 ε-viniferin 和 johorenol A 与标准抗生素万古霉素和利奈唑胺联合应用对 MRSA ATCC 33591 和 HUKM 临床分离株的作用。分别测定了各化合物的最小抑菌浓度 (MIC) 值和联合药物的部分抑菌浓度指数 (FICI) 值。只有棋盘试验的协同结果才会通过时间杀伤试验来证实其杀菌率。ε-viniferin 对 ATCC 33591 的 MIC 值和 johorenol A 对两种菌株的 MIC 值均为 0.05mg/mL，而 HUKM 菌株对 0.1mg/mL 的 ε-viniferin 敏感。MDC 研究表明，只有 ε-viniferin 与万古霉素之间的组合对 ATCC 33591 （FICI 0.25）和 HUKM （FICI 0.19）具有协同作用。其他所有组合（ε-viniferin-利奈唑胺、johorenol A-万古霉素和 johorenol A-利奈唑胺）均为无关或相加作用。然而，尽管 FICI 值显示 ε-viniferin-万古霉素具有协同作用，但 TKA 分析显示对两种菌株均具有抑菌作用的拮抗作用。因此，ε-viniferin 可被视为一种抑菌性白藜芦醇类化合物，因为它拮抗了万古霉素的杀菌活性。这些发现与之前报道的 ε-viniferin 与万古霉素协同作用的观点相矛盾，但揭示了它作用于与万古霉素作用相似的位点，可能在细菌膜蛋白上。因此，这种组合具有很大的潜力，可在未来作为一种替代治疗方法，进一步研究和开发用于治疗耐甲氧西林金黄色葡萄球菌。
