Department of Respiratory Medicine, the First Hospital of Jilin University, Changchun, China.
Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
J Appl Microbiol. 2020 Sep;129(3):532-540. doi: 10.1111/jam.14635. Epub 2020 Mar 23.
To examine the synergistic effect of calycosin combined with polymyxin B against various mcr-1-positive bacterial strains.
In this study, we found a potential inhibitor of MCR-1, calycosin, that could significantly restore the antibacterial activity of polymyxin B. The synergistic effect of calycosin combined with polymyxin B against various mcr-1-positive bacterial strains was confirmed by checkerboard minimum inhibitory concentration assays, time-kill curve assays and disk diffusion assays. The fractional inhibitory concentration indexes ranged from 0·15 ± 0·03 to 0·28 ± 0·05, and the zones of inhibition increased from 13·33 ± 0·47 to 17·67 ± 0·47 mm with the combined therapy of calycosin and polymyxin B. In addition, the combined therapy significantly reduced the number of bacteria in the medium. However, at the concentrations required for the synergistic effect with polymyxin B, calycosin alone showed no effect on bacterial growth or MCR-1 production. Calycosin treatment exhibited no cytotoxicity to HeLa cells or A549 cells at calycosin concentrations below 32 µg ml .
Therefore, our results suggested that calycosin could be used as a potential MCR-1 inhibitor to restore the bactericidal effect of polymyxin B without affecting bacterial viability or existing cytotoxicity.
The synergistic effect of calycosin combined with polymyxin B against various mcr-1-positive bacterial strains paves the way for future pharmaceutical applications of calycosin in fighting mcr-1-positive bacterial infections.
研究毛蕊异黄酮与黏菌素 B 联合使用对各种 mcr-1 阳性细菌株的协同作用。
在这项研究中，我们发现了一种潜在的 MCR-1 抑制剂——毛蕊异黄酮，它可以显著恢复黏菌素 B 的抗菌活性。棋盘微量稀释法、时间杀伤曲线和药敏纸片扩散法证实了毛蕊异黄酮与黏菌素 B 联合使用对各种 mcr-1 阳性细菌株的协同作用。毛蕊异黄酮与黏菌素 B 联合使用的部分抑菌浓度指数范围为 0.15±0.03 至 0.28±0.05，抑菌圈直径从 13.33±0.47 增加到 17.67±0.47mm。此外，联合治疗显著减少了培养基中的细菌数量。然而，在与黏菌素 B 协同作用所需的浓度下，毛蕊异黄酮单独使用对细菌生长或 MCR-1 产生没有影响。毛蕊异黄酮处理在低于 32µg ml-1 的浓度下对 HeLa 细胞或 A549 细胞没有细胞毒性。
因此，我们的研究结果表明，毛蕊异黄酮可作为一种潜在的 MCR-1 抑制剂，在不影响细菌活力或现有细胞毒性的情况下恢复黏菌素 B 的杀菌作用。
毛蕊异黄酮与黏菌素 B 联合使用对各种 mcr-1 阳性细菌株的协同作用为毛蕊异黄酮在治疗 mcr-1 阳性细菌感染方面的未来药物应用铺平了道路。
