Centrale Marseille, CNRS, iSm2 UMR 7313, Aix Marseille University, 13397 Marseille, France.
Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon.
Toxins (Basel). 2019 Sep 3;11(9):514. doi: 10.3390/toxins11090514.
Filamentous fungi, although producing noxious molecules such as mycotoxins, have been used to produce numerous drugs active against human diseases such as paclitaxel, statins, and penicillin, saving millions of human lives. Cyclodepsipeptides are fungal molecules with potentially adverse and positive effects. Although these peptides are not novel, comparative studies of their antimicrobial activity, toxicity, and mechanism of action are still to be identified. In this study, the fungal cyclohexadepsipeptides enniatin (ENN) and beauvericin (BEA) were assessed to determine their antimicrobial activity and cytotoxicity against human cells. Results showed that these peptides were active against Gram-positive bacteria, and fungi, but not against Gram-negative bacteria. ENN and BEA had a limited hemolytic effect, yet were found to be toxic at low doses to nucleated human cells. Both peptides also interacted with bacterial lipids, causing low to no membrane permeabilization, but induced membrane depolarization and inhibition of macromolecules synthesis. The structure-activity analysis showed that the chemical nature of the side chains present on ENN and BEA (either -propyl, -butyl, or phenylmethyl) impacts their interaction with lipids, antimicrobial action, and toxicity.
丝状真菌虽然会产生霉菌毒素等有害物质，但也被用来生产许多对抗人类疾病有效的药物，如紫杉醇、他汀类药物和青霉素，挽救了数百万人的生命。环二肽是具有潜在不良反应和积极作用的真菌分子。虽然这些肽类并不新颖，但它们的抗菌活性、毒性和作用机制的比较研究仍有待确定。在这项研究中，评估了真菌环己二肽类化合物恩镰菌素（ENN）和 beauvericin（BEA），以确定它们对人类细胞的抗菌活性和细胞毒性。结果表明，这些肽类对革兰氏阳性菌和真菌具有活性，但对革兰氏阴性菌没有活性。ENN 和 BEA 具有有限的溶血作用，但在低剂量下对有核人细胞有毒。这两种肽还与细菌脂质相互作用，导致低至无膜通透性，但诱导膜去极化和抑制大分子合成。结构-活性分析表明，ENN 和 BEA 上存在的侧链（丙基、丁基或苄基）的化学性质影响它们与脂质的相互作用、抗菌作用和毒性。
