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Chemical genomics to combat Fusarium and mitigate DON production in Fusarium graminearum

Principal Investigator: Rajagopal Subramaniam

Research Institution: Ottawa Research and Development Centre, Agriculture and Agri-Food Canada (AAFC)

Timeline: January 2014 – March 2018

Objectives:

  • Determine the efficacy of bio-fungicide compounds to combat Fusarium Head Blight (FHB) with respect to application timing, dosage of bio-fungicide compounds and Fusarium graminearum strains with different chemotypes (3-ADON, 15-ADON and NIV).
  • Identify bio-fungicide compounds that mitigate deoxynivalenol (DON) production.

Impacts:

  • The identification of environmentally friendly bio-pesticides that mitigate Fusarium growth and DON production.
  • The identification of biochemical pathways involved in fungal growth and mycotoxin production.
  • The identification of synthetic bio-fungicide cocktails that provide Canadian farmers with novel strategies to combat current and emerging diseases.

Scientific Summary:

Fusarium graminearum is an economically significant pathogen of cereal crops, such as wheat, barley, maize, oats and rye, that causes Fusarium head blight (FHB) disease. FHB is also accompanied by the accumulation of various mycotoxins that represent a serious health issue when present at high concentrations. Although fungicide treatments and improved agronomic practices can help to reduce the Fusarium problem in low to moderate infection years, epidemic prevention requires an integrated management approach. In Canada, there are only few active ingredients registered to suppress F. graminearum as a foliar or seed treatment in cereals.

Chemical genetics can be used to develop and deploy new bio-pesticides that are both environmentally friendly and more importantly, specific to the pathogen to be controlled. Chemical genetics is based on the ability of small chemical compounds to bind to biological molecules and alter their function. We developed a high throughput screening strategy and have identified eight families of compounds that mitigated Fusarium growth and interfered with DON production. One compound, Antofine, isolated from a plant species Vincetoxicum rossicum, showed in greenhouse studies approximately a 40% reduction in FHB symptoms on wheat heads when sprayed with Antofine prior to Fusarium infection. By using yeast as a model organism, we have also identified six target genes of Antofine in Fusarium. Since these genes are responsible for fungal growth, it will enable us to develop a designer cocktail suitable to combat FHB and other fungal-caused diseases and reduce mycotoxin contamination.

Final Results:

The fungal target of Antofine was identified as RRD1, part of the Target of Rapamycin (TOR) pathway in Yeast and Fusarium (Mogg et al., 2019). In addition to Antofine, nine compounds belonging to eight distinct chemical families were identified. TOR is an important pathway conserved in all eukaryotes and, as such, nine compounds representing from each chemical family group were studied for their interaction with the TOR pathway. Ongoing studies may uncover additional inhibitors of the TOR pathway, which will be pursued for commercial potential.

A screen of ~600 compounds resulted in 23 hits that resulted in inhibition of Tri5 expression. A follow-up validation screen with the same 23 compounds resulted in the identification of three compounds that showed changes in DON production without having any effect on Fusarium growth. This indicated that these compounds may function as adjuvant molecules. That is, they may augment the activity of fungicides.

Identification of adjuvant molecules resulted in a joint collaboration with two companies (Vive and Arysta) and a collaborative project has been funded within the Canadian Agricultural Partnership Bioproducts Cluster.

Preliminary experiments are being undertaken by Vive Crop Protection to assess suitability of lead candidates for micro-formulation with their allosperse proprietary encapsulation technology. Initial materials will be provided by ORDC scientists. Allosperse technology works by encapsulating active ingredients in a cross-linked acrylic copolymer structure. Following preliminary assessment, micro-formulation of adjuvants will be carried out for in planta efficacy testing.

External Funding Partners:

Growing Forward 2’s Agri Innovation Program (AIP).

This project was funded in part through Growing Forward 2, a federal-provincial-territorial initiative.

Project Related Publications:

Mogg C, Bonner C, Wang L, Schernthaner J, Smith M, Desveaux D, Subramaniam, R. 2019. Genomic identification of the TOR signaling pathway as a target of the plant alkaloid Antofine in the phytopathogen Fusarium graminearum. mBio DOI: 10.1128/mBio.00792-19.

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