Plant defensin MtDef4–derived antifungal peptide with multiple modes of action and potential as a bio–inspired fungicide

Tetorya, Meenakshi; Li, Hui; Djami‐Tchatchou, Arnaud Thierry; Buchko, Garry W.; Czymmek, Kirk J.; Shah, Dilip M.

doi:10.1111/mpp.13336

Plant defensin MtDef4–derived antifungal peptide with multiple modes of action and potential as a bio–inspired fungicide

Journal Article · Mon Apr 10 00:00:00 EDT 2023 · Molecular Plant Pathology

DOI:https://doi.org/10.1111/mpp.13336· OSTI ID:2471561

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Donald Danforth Plant Science Center, St Louis, MO (United States)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Washington State University, Pullman, WA (United States)

Chemical fungicides have been instrumental in protecting crops from fungal diseases. However, increasing fungal resistance to many of the single-site chemical fungicides calls for the development of new antifungal agents with novel modes of action (MoA). The sequence-divergent cysteine-rich antifungal defensins with multisite MoA are promising starting templates for design of novel peptide-based fungicides. Here, we experimentally tested such a set of 17-amino-acid peptides containing the γ-core motif of the antifungal plant defensin MtDef4. These designed peptides exhibited antifungal properties different from those of MtDef4. Focused analysis of a lead peptide, GMA4CG_V6, showed that it was a random coil in solution with little or no secondary structure elements. Additionally, it exhibited potent cation-tolerant antifungal activity against the plant fungal pathogen Botrytis cinerea, the causal agent of grey mould disease in fruits and vegetables. Its multisite MoA involved localization predominantly to the plasma membrane, permeabilization of the plasma membrane, rapid internalization into the vacuole and cytoplasm, and affinity for the bioactive phosphoinositides phosphatidylinositol 3-phosphate (PI3P), PI4P, and PI5P. The sequence motif RRRW was identified as a major determinant of the antifungal activity of this peptide. While topical spray application of GMA4CG_V6 on Nicotiana benthamiana and tomato plants provided preventive and curative suppression of grey mould disease symptoms, the peptide was not internalized into plant cells. Our findings open the possibility that truncated and modified defensin-derived peptides containing the γ-core sequence could serve as promising candidates for further development of bio-inspired fungicides.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: National Science Foundation (NSF); USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2471561

Alternate ID(s):: OSTI ID: 2568167

Report Number(s):: PNNL-SA--174119

Journal Information:: Molecular Plant Pathology, Journal Name: Molecular Plant Pathology Journal Issue: 8 Vol. 24; ISSN 1464-6722

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

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54 ENVIRONMENTAL SCIENCES
Botrytis cinerea
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antifungal activity
bio-inspired fungicides
circular dichroism spectroscopy
cysteine-rich
defensin-derived peptides
defensins
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Plant defensin MtDef4–derived antifungal peptide with multiple modes of action and potential as a bio–inspired fungicide

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