UW researcher part of collaborative team that unveils next-generation fungicide

The impact of fungal pathogens on global agriculture is staggering, with gray mold fungus alone infecting more than 200 plant species and causing losses exceeding $10 billion annually worldwide. 

Similarly, the rice blast fungus annually destroys more than 50 million tons of rice – enough to feed one billion people.

An increase in fungicide application has given rise to resistance to these devastating pathogens. The changing population dynamics of fungal pathogens under global warming also make monitoring and prevention increasingly difficult.

A University of Wyoming (UW) researcher was part of a recent study which has led to the design and development of a synthetic sensor using the bioluminescence resonance energy transfer (BRET) technology to monitor an important enzymatic process in autophagy biogenesis.

The sensor can be used for the identification of promising fungicide candidates capable of inhibiting the fungal autophagy process.

“We have designed and developed a synthetic sensor to monitor an important enzymatic process in autophagy biogenesis of gray mold. With the sensor, we have performed high-throughput drug screening to identify chemical inhibitors for fungal autophagy,” says Eunsook Park, an assistant professor in UW’s Department of Molecular Biology.

Published study 

Park was a co-corresponding author of a paper titled “Attenuation of phytofungal pathogenicity of Ascomycota by autophagy modulators,” which was published recently in Nature Communications, an open access, multidisciplinary journal dedicated to publishing high-quality research in all areas of the biological, health, physical, chemical, Earth, social, mathematical, applied and engineering sciences.

Jongchan Woo, a senior research scientist in UW’s Department of Molecular Biology, and Seungmee Jung, a UW graduate student working in the Eunsook Park Lab, were co-first authors of the paper.

Scientists from the University of California-Davis, Texas A&M University and Seoul National University in South Korea were also part of the study.

The study not only sheds light on the intricate relationship between autophagy and fungal pathogenicity, but also marks a significant step toward the development of effective and sustainable fungicides for global agricultural protection, Park says.

“We have identified ebselen, a small chemical compound, as an inhibitor. We have proven ebselen is an effective fungicide against phytofungal pathogens,” Park says. “Ebselen is a new drug candidate under clinical trial for human diseases, indicating ebselen is relatively safe for humans compared to existing fungicides against plant fungal pathogens.”

During the study, researchers demonstrated ebselen effectively prevented fungal infection in agronomically and horticulturally important hosts, such as grapes, strawberries, tomatoes, rice and roses. Additionally, ebselen has been known to have a clinical benefit for human noise-induced hearing loss, Park says.

Importance of authophagy 

“Our drug screening platform using the synthetic sensor is easy and versatile for identifying drug candidates targeting autophagy involved in certain human diseases,” Park says.

Autophagy means “self-eating” in Greek, according to Park. 

Autophagy is a fundamental process found in cells which is preserved in different species, from yeast to humans. Autophagy controls the breakdown of both cellular parts that do not work and toxic materials and then recycles them within the cell in response to external stimuli. 

Fungal autophagy plays pivotal roles in the life cycle and disease development of fungal pathogens.

“Autophagy, a crucial intracellular process for maintaining eukaryotic homeostasis, has recently gained importance, particularly in its role in fungal pathogenicity,” Park says. “This indicates targeting the autophagy process is a promising strategy for the development of novel fungicides.”

The study began a decade ago at the University of California-Davis, where Park and Woo were senior research specialists at the time. The two continued their research at Seoul National University, where Park was a non-tenure track assistant professor for two years. 

Park and Woo eventually landed at UW and conducted the final stages of their research.

The study was funded by National Science Foundation-Established Program to Stimulate Competitive Research and National Institutes of Health-INBRE IDeA Networks of Biomedical Research Excellence grants.

This story was originally published on UW News staff on March 27.