Enniatin A1, A Natural Compound with Bactericidal Activity against Mycobacterium tuberculosis In Vitro

文献类型： 外文期刊

第一作者： Wang, Gaoyan

作者： Wang, Gaoyan;Dong, Wenqi;Lu, Hao;Lu, Wenjia;Feng, Jiajia;Wang, Xiangru;Chen, Huanchun;Tan, Chen;Liu, Manli;Tan, Chen

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关键词： Mycobacterium tuberculosis; natural compound; enniatin A1; bactericidal; synergy; membrane potential

期刊名称：MOLECULES （ 影响因子：4.411； 五年影响因子：4.587 ）

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年卷期： 2020 年 25 卷 1 期

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收录情况： SCI

摘要： Background: 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. Methods: 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 Mycobacterium tuberculosis (M. tuberculosis) 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 M. tuberculosis. 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 M. tuberculosis after exposure to enniatin A1. Results: We identified enniatinA1 as a potential antibacterial agent against M. tuberculosis, against which it showed strong selectivity. Enniatin A1 exhibited a time-concentration-dependent bactericidal effect against M. tuberculosis, and it displayed synergy with rifamycin, amikacin, and ethambutol. After exposure to enniatinA1, the membrane potential and intracellular ATP levels of M. tuberculosis was significantly decreased. Conclusions: Enniatin A1 exhibits the positive potential anti-tuberculosis agent characteristics.

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