Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China.
Molecules. 2010 Oct 29;15(11):7750-62. doi: 10.3390/molecules15117750.
The active multidrug efflux pump (EP) has been described as one of the mechanisms involved in the natural drug resistance of bacteria, such as mycobacteria. As a result, the development of efflux pumps inhibitors (EPIs) is an important topic. In this study, a checkerboard synergy assay indicated that farnesol both decreased the minimum inhibitory concentration (MIC) of ethidium bromide (EtBr) 8-fold against Mycobacterium smegmatis (M. smegmatis) mc²155 ATCC 700084 when incorporated at a concentration of 32 μg/mL (FICI = 0.625) and decreased MIC 4-fold at 16 μg/mL (FICI = 0.375). Farnesol also showed synergism when combined with rifampicin. A real-time 96-well plate fluorometric method was used to assess the ability of farnesol to inhibit EPs in comparison with four positive EPIs: chlorpromazine, reserpine, verapamil, and carbonyl cyanide m-chlorophenylhydrazone (CCCP). Farnesol significantly enhanced the accumulation of EtBr and decreased the efflux of EtBr in M. smegmatis; these results suggest that farnesol acts as an inhibitor of mycobacterial efflux pumps.
主动型多药外排泵（EP）已被描述为参与细菌（如分枝杆菌）天然药物耐药性的机制之一。因此，外排泵抑制剂（EPIs）的开发是一个重要的课题。在这项研究中，棋盘式协同测定表明，法尼醇在 32μg/mL 浓度下（FICI=0.625）可使溴化乙锭（EtBr）对耻垢分枝杆菌（M. smegmatis）mc²155 ATCC 700084 的最小抑菌浓度（MIC）降低 8 倍，当浓度为 16μg/mL 时（FICI=0.375）MIC 降低 4 倍。法尼醇与利福平联合使用时也表现出协同作用。实时 96 孔板荧光法用于评估法尼醇与四种阳性 EPIs（氯丙嗪、利血平、维拉帕米和羰基氰化物 m-氯代苯腙（CCCP））抑制 EP 的能力。法尼醇显著增加了 EtBr 的蓄积并减少了 EtBr 在耻垢分枝杆菌中的外排；这些结果表明法尼醇可作为分枝杆菌外排泵的抑制剂。
