Abstract
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.
Highlights
Tuberculosis remains a global infectious disease that poses a serious threat to human health, causing about 10 million new cases and more than 1.5 million deaths in 2017 [1]
Bedaquiline is an effective drug against both wild-type and drug-resistant M. tuberculosis and it has been approved by the Food and Drug Administration (FDA) in 2012 for curing multidrug-resistant tuberculosis (MDR-TB) [9]
Natural products remain a rich source of new drugs [25], and despite the current reduced interest in natural compounds, natural products, derivatives of natural products, and related lead compound structures remain potential sources of novel drugs [26]
Summary
Tuberculosis remains a global infectious disease that poses a serious threat to human health, causing about 10 million new cases and more than 1.5 million deaths in 2017 [1]. Drug screening efforts have been made to detect new antibiotics or compound structures with new antibacterial mechanism by whole-cell or phenotypic high-throughput screening methods and to evaluate the anti-tuberculosis activity of natural products from large compound libraries [5,6,7]. 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.
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