Peptides obtained by targeted modifications of a natural Trichoderma peptaibol protect plants from grey mold disease and downy mildew

Fungal species belonging to the Trichoderma genus are commonly used as biocontrol agents against several crop pathogens. Among their secondary metabolites, peptaibols are helical, antimicrobial peptides structurally stable even under extreme pH and temperature conditions. The promise of peptaibols as agrochemicals is however hampered by poor water solubility, which inhibits efficient delivery for practical use in crop protection. Using a versatile synthetic strategy, based on green chemistry procedures, we produced water-soluble peptaibol analogs of the 11-mer lipopeptaibol trichogin GA IV, naturally produced by Trichoderma longibrachiatum. These newly synthesized peptides were tested against the important plant pathogens Botrytis cinerea and Plasmopara viticola. Compared to native trichogin, which was inactive against the tested pathogens, some peptide analogs resulted particularly effective at low micromolar concentrations against both pathogens, while others were effective only against one of them. The most effective peptides significantly reduced disease symptoms by P. viticola on grapevine leaves and by B. cinerea on grapevine leaves, ripe grape berries and tomato leaves. Our results suggest that trichogin-derived peptides do not prime plant defenses but protect plant tissues by inhibiting spore germination on the host surface. An in-depth conformational analysis featuring a 3D-structure-activity relationship study indicated that the relative spatial position of cationic residues in the sequence is crucial for increasing peptide fungicidal activity. Besides, effective peptides maintain the right-handed helical structure even in the presence of the pathogen. Further studies will help clarify the mode of action of these antimicrobial peptides.