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.
Crops are threatened by numerous fungal diseases that can adversely affect the availability and quality of agricultural commodities. In addition, some of these fungal phytopathogens have the capacity to produce mycotoxins that pose a serious health threat to humans and livestock. To facilitate the transition towards sustainable environmentally friendly agriculture, there is an urgent need to develop innovative methods allowing a reduced use of synthetic fungicides while guaranteeing optimal yields and the safety of the harvests. Several defensins have been reported to display antifungal and even—despite being under-studied—antimycotoxin activities and could be promising natural molecules for the development of control strategies. This review analyses pioneering and recent work addressing the bioactivity of defensins towards fungal phytopathogens; the details of approximately 100 active defensins and defensin-like peptides occurring in plants, mammals, fungi and invertebrates are listed. Moreover, the multi-faceted mechanism of action employed by defensins, the opportunity to optimize large-scale production procedures such as their solubility, stability and toxicity to plants and mammals are discussed. Overall, the knowledge gathered within the present review strongly supports the bright future held by defensin-based plant protection solutions while pointing out the obstacles that still need to be overcome to translate defensin-based in vitro research findings into commercial products.
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