Valentin Leannec-Rialland, Alejandro Cabezas-Cruz, Vessela Atanasova, Sylvain Chereau, Nadia Ponts, Miray Tonk, Andreas Vilcinskas, Nathalie Ferrer, James J. Valdés and Florence Richard-Forget (2021). Structural and physicochemical determinants governing the efficiency of tick defensin gamma-core to control Fusarium graminearum and the production of type B trichothecene mycotoxins. Scientific Reports 11:7962 https://doi.org/10.1038/s41598-021-86904-w

Fusarium graminearum is a major fungal pathogen affecting small grain cereals and maize with significant economic impact in many cereal-growing areas worldwide. The mycotoxins produced by F. graminearum, mainly type B trichothecenes (TCTB), are toxic to humans and animals. As heat-stable molecules, TCTB are not fully eliminated during manufacturing of cereal-based food and feed. Therefore, the best way to minimize TCTB contamination is to develop sustainable, and environment-friendly pre-harvest control strategies. Defensins are cyclic peptides of low molecular weight with a conserved gamma-core motif crucial for antimicrobial activity. Herein we show that treatment with the reduced form of the gamma-core of the tick defensin DefMT3, referred to as TickCore3 (TC3), decreases F. graminearum mycelial growth and abrogates the production of TCTB in vitro. The oxidized forms of TC3 lose mycelia growth activity, but retain inhibitory activity on TCTB production. 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 Cys residues of TC3 with methyl groups (CH3) reduces the antifungal and anti-mycotoxin activities of TC3. Major loss of function was observed when Cys9 or Cys11 were capped with CH3. Substitutions of the positively-charged residues Lys6 or Arg7 by Thr had the highest and the lesser impact, respectively, on the anti-mycotoxin activity of TC3. We conclude that the binding of all positive residues 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. The discoveries in this study can be the foundation for developing novel and environment-friendly strategies for controlling the crop pest F. graminearum.

An international collaboration between Alejandro Cabezas-Cruz (UMR BIPAR, France), Florence Forget (UR 1264 MycSA, France), James J Valdés (Institute of Parasitology, Czech Republic), Miray Tonk (Institute for Insect Biotechnology, Germany).