State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
Hubei Biopesticide Engineering Research Centre, Hubei Academy of Agricultural Sciences, Wuhan 430070, Hubei, China.
Molecules. 2019 Dec 20;25(1):38. doi: 10.3390/molecules25010038.
: Tuberculosis remains a global disease that poses a serious threat to human health, but there is lack of new and available anti-tuberculosis agents to prevent the emergence of drug-resistant strains. To address this problem natural products are still potential sources for the development of novel drugs. : A whole-cell screening approach was utilized to obtain a natural compound enniatin A1 from a natural products library. The target compound's antibacterial activity against () was evaluated by using the resazurin reduction micro-plate assay (REMA) method. The cytotoxicity of the compound against Vero cells was measured to calculate the selectivity index. The intracellular inhibition activity of enniatin A1 was determined. We performed its time-kill kinetic assay against . We first tested its synergistic effect in combination with the first and second-line anti-tuberculosis drugs. Finally, we measured the membrane potential and intracellular ATP levels of after exposure to enniatin A1. : We identified enniatinA1 as a potential antibacterial agent against , against which it showed strong selectivity. Enniatin A1 exhibited a time-concentration-dependent bactericidal effect against , and it displayed synergy with rifamycin, amikacin, and ethambutol. After exposure to enniatinA1, the membrane potential and intracellular ATP levels of was significantly decreased. : Enniatin A1 exhibits the positive potential anti-tuberculosis agent characteristics.
: 结核病仍然是一种全球性疾病，对人类健康构成严重威胁，但缺乏新的可用的抗结核药物来预防耐药菌株的出现。为了解决这个问题，天然产物仍然是开发新型药物的潜在来源。: 采用全细胞筛选方法从天然产物文库中获得天然化合物恩曲他滨 A1。采用 Resazurin 还原微量板测定法 (REMA) 评价目标化合物对 （）的抗菌活性。测定化合物对 Vero 细胞的细胞毒性，计算选择性指数。测定恩曲他滨 A1 的细胞内抑制活性。我们对 进行了时间杀伤动力学测定。我们首先测试了它与一线和二线抗结核药物联合使用的协同作用。最后，我们测量了暴露于恩曲他滨 A1 后 的膜电位和细胞内 ATP 水平。: 我们确定恩曲他滨 A1 是一种有潜力的抗结核药物，对其具有很强的选择性。恩曲他滨 A1 对 表现出时间浓度依赖性杀菌作用，与利福霉素、阿米卡星和乙胺丁醇具有协同作用。暴露于恩曲他滨 A1 后， 的膜电位和细胞内 ATP 水平显著降低。: 恩曲他滨 A1 表现出阳性的潜在抗结核药物特征。
