Leannec-Rialland Valentin, Cabezas-Cruz Alejandro, Atanasova Vessela, Chereau Sylvain, Ponts Nadia, Tonk Miray, Vilcinskas Andreas, Ferrer Nathalie, Valdés James J, Richard-Forget Florence
Université de Bordeaux, INRAE, Mycology and Food Safety (MycSA), 33882, Villenave d'Ornon, France.
Anses, INRAE, Ecole Nationale Vétérinaire D'Alfort, UMR BIPAR, Laboratoire de Santé Animale, 94700, Maisons-Alfort, France.
Sci Rep. 2021 Apr 12;11(1):7962. doi: 10.1038/s41598-021-86904-w.
Fusarium graminearum is a major fungal pathogen affecting crops of worldwide importance. F. graminearum produces type B trichothecene mycotoxins (TCTB), which are not fully eliminated during food and feed processing. Therefore, the best way to minimize TCTB contamination is to develop prevention strategies. Herein we show that treatment with the reduced form of the γ-core of the tick defensin DefMT3, referred to as TickCore3 (TC3), decreases F. graminearum growth and abrogates TCTB production. The oxidized form of TC3 loses antifungal activity, but retains anti-mycotoxin activity. Molecular dynamics show that TC3 is recruited by specific membrane phospholipids in F. graminearum and that membrane binding of the oxidized form of TC3 is unstable. Capping each of the three cysteine residues of TC3 with methyl groups reduces its inhibitory efficacy. Substitutions of the positively-charged residues lysine (Lys) 6 or arginine 7 by threonine had the highest and the lesser impact, respectively, on the anti-mycotoxin activity of TC3. We conclude that the binding of linear TC3 to F. graminearum membrane phospholipids is required for the antifungal activity of the reduced peptide. Besides, Lys6 appears essential for the anti-mycotoxin activity of the reduced peptide. Our results provide foundation for developing novel and environment-friendly strategies for controlling F. graminearum.
禾谷镰刀菌是一种影响全球重要农作物的主要真菌病原体。禾谷镰刀菌产生B型单端孢霉烯族毒素（TCTB），在食品和饲料加工过程中这些毒素无法被完全清除。因此，将TCTB污染降至最低的最佳方法是制定预防策略。在此我们表明，用蜱防御素DefMT3的γ核心的还原形式（称为蜱核心3，即TC3）进行处理，可减少禾谷镰刀菌的生长并消除TCTB的产生。TC3的氧化形式失去抗真菌活性，但保留抗毒素活性。分子动力学表明，TC3被禾谷镰刀菌中的特定膜磷脂招募，且TC3氧化形式的膜结合不稳定。用甲基封端TC3的三个半胱氨酸残基中的每一个都会降低其抑制效力。用苏氨酸分别取代带正电荷的赖氨酸（Lys）6或精氨酸7，对TC3的抗毒素活性影响最大和最小。我们得出结论，线性TC3与禾谷镰刀菌膜磷脂的结合是还原肽抗真菌活性所必需的。此外，Lys6似乎对还原肽的抗毒素活性至关重要。我们的结果为开发控制禾谷镰刀菌的新型环保策略提供了基础。
