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

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.

Fusarium Mycotoxins Enniatins: An Updated Review of Their Occurrence, the Producing Fusarium Species, and the Abiotic Determinants of Their Accumulation in Crop Harvests

“…109,112−115 Indeed, the in vitro cytotoxicity properties and, particularly, anticancer activities make ENNs a potential drug for human health diseases. 116,117 The previous studies consistently show that ENNs can be produced on a broad spectrum of carbon sources and that NaNO 3 was the best inorganic nitrogen source, although variation between isolates was highlighted. Thus, for F. oxysporum and F. avenaceum isolates, sucrose was reported as one of the optimal sources of carbon for ENN production and lactose was the less permissive source, whereas the highest ENN yield was obtained with lactose for F. sambucinum.…”

“…However, studies addressing the impact of abiotic factors have been mainly concentrated on legislated mycotoxins, intensely on aflatoxin, ochratoxin, DON, and fumonisin, and only limited data are available with regard to environmental factors underpinning the production of ENNs. Most of the published reports have investigated the influence of nutritional factors, mainly carbon and nitrogen sources, with the aim to optimize the yield of these cyclic hexadepsipeptides. ,− Indeed, the in vitro cytotoxicity properties and, particularly, anticancer activities make ENNs a potential drug for human health diseases. , The previous studies consistently show that ENNs can be produced on a broad spectrum of carbon sources and that NaNO 3 was the best inorganic nitrogen source, although variation between isolates was highlighted. Thus, for F.…”

Repurposing an Antioxidant to Kill Mycobacterium tuberculosis by Targeting the 50S Subunit of the Ribosome

“…The minimum inhibitory concentration (MIC) was determined using a resazurinreducing microplate assay (REMA) [18]. Drugs were serially diluted twofold in 96-well plates supplemented with 100 µL of 7H9 medium.…”

Fungal-derived compounds and mycogenic nanoparticles with antimycobacterial activity: a review

“…[31]. F. avenaceum DAOM 196,490 was found to produce several enniatins, among them was enniatin A1 (29) which was tested in another study against M. tuberculosis H37Rv, M. tuberculosis H37Ra, M. bovis, M. bovis BCG and M. smegmatis mc 2 155 [32]. Enniatin A1 (29) was found to be slightly more active against virulent M. tuberculosis H37Rv (MIC = 1 µg/mL), compared to the avirulent M. tuberculosis H37Ra (MIC = 2 µg/mL).…”