A promising new antifungal agent to fight annihilating harvest disease has been identify by researcher at the University of California , Davis . The chemical , ebselen , prevented fungal infections in apples , grapeshot , strawberries , tomatoes and roses , and improved symptoms of pre - existent fungal contagion in rice .
Fungal pathogen account for almost a quarter of global crop losses . In the United States , these loss amount to around $ 150 billion per twelvemonth . However , fungicide development has been slow for the past 50 years , mostly because investigator have had difficulty identifying molecular nerve tract to target . In a new report published Feb. 29 in Nature Communications , UC Davis investigator identified fungicide candidates that direct autophagy , a cellular recycling cognitive process that was recently exhibit as all important for fungal pathogenicity .
Using a novel screening method acting base on bioluminescence , the investigator identified 30 chemical that stamp down a key enzymatic pace in fungous autophagy . The most hopeful candidate , ebselen , has been shown to have anti - inflammatory and neuroprotective properties in man and was more efficient at forbid in vitro fungal growth than presently available fungicide .
" inhibit autophagy significantly reduces the pathogenicity of several devastating fungous pathogen , " pronounce fourth-year source Savithramma Dinesh - Kumar , a professor and chairwoman in the Department of Plant Biology . " Our findings provide molecular insights that will help oneself to develop the next multiplication of antifungal compounds . "
A novel fungicide targetAutophagy is an essential physical process in fungi , plant life and creature cell that enable them to recycle cellular components and remove toxic waste products . Because recent study have shown that autophagy is involved in fungous pathogenicity , the researchers conjecture that forget autophagy would subdue fungal contagion . They set out to discover chemicals that inhibit autophagy in fungi , focusing on one key step in the pathway — the segmentation of the ATG8 protein by the enzyme ATG4 .
To describe chemicals that inhibit this reaction , the squad developed a examination that allowed them to visualize when the reaction go on and when it was blocked . Then , they try the fungi ’s ability to enzymatically cleave ATG8 in the presence of 2,700 different chemicals from a program library of FDA - approved compounds . This method acting has advantages over other showing method in that it appropriate a great turn of chemicals to be test very apace .
all told , the researcher identified 30 chemical substance compounds that inhibited segmentation and 14 compound that raise segmentation . They selected the most effective inhibitor , ebselen , for further testing .
protect plants from fungal pathogensIn petri - dish experimentation , ebselen prevented fungal germination and growth better than drug that are on the market flop now , Dinesh - Kumar said . The squad also showed that ebselen prevented fungous infections in a range of works species while demonstrating curative potential : When the researchers applied the chemical to the leaves of rice plant that were antecedently infect with Elmer Reizenstein gust fungus , it effectively eliminated contagion .
" We think ebselen will mainly be useful for protect plants against future infection , but it can also partly overtake existing infection if it is used early enough , " pronounce Dinesh - Kumar .
Although the team ’s preliminary testing point that ebselen specifically inhibit autophagy in fungi , more testing is require to guarantee its base hit .
" Since autophagy is extremely conserved across different organisms , include homo , more work needs to be done to test the cross reactivity of the drug , " said Dinesh - Kumar .
The UC Davis researcher also project to use their screening method acting to test even more chemicals for their ability to inhibit autophagy .
" The chemic space is very big , and some chemical substance libraries have more than 50,000 compounds , " said Dinesh - Kumar . " The next measure will be to screen for extra autophagy modulators that might help control not just plant fungal pathogen , but also human fungal pathogen . "
extra author on the study are : Tatiana V. Roubtsova , Celine Caseys , Dan Kliebenstein and Richard M. Bostock , UC Davis ; Jongchan Woo , Seungmee Jung and Eunsook Park , University of Wyoming , Laramie ; Martin B. Dickman , Honghong Zhang and Yurong Li , Texas A & M University ; Kyung - Nam Kim , Sejong University , Korea ; and Seongbeom Kim , Hyunjung Chung , Yong - Hwan Lee and Doil Choi , Seoul National University , Korea .
beginning : ucdavis.edu
