| Abstract |
Autophagy in eukaryotes functions to maintain homeostasis by degradation and recycling of long-lived and unwanted cellular materials. Autophagy plays important roles in pathogenicity of various fungal pathogens, suggesting that autophagy is a novel target for development of antifungal compounds. Here, we describe bioluminescence resonance energy transfer (BRET)-based high-throughput screening (HTS) strategy to identify compounds that inhibit fungal ATG4 cysteine protease-mediated cleavage of ATG8 that is critical for autophagosome formation. We identified ebselen (EB) and its analogs ebselen oxide (EO) and 2-(4-methylphenyl)−1,2-benzisothiazol-3(2H)-one (PT) as inhibitors of fungal pathogens Botrytis cinerea and Magnaporthe oryzae ATG4-mediated ATG8 processing. The EB and its analogs inhibit spore germination, hyphal development, and appressorium formation in Ascomycota pathogens, B. cinerea, M. oryzae , Sclerotinia sclerotiorum and Monilinia fructicola . Treatment with EB and its analogs significantly reduced fungal pathogenicity. Our findings provide molecular insights to develop the next generation of antifungal compounds by targeting autophagy in important fungal pathogens. |
| Authors |
Jongchan Woo  , Seungmee Jung  , Seongbeom Kim , Yurong Li , Hyun‐Jung Chung , Tatiana V. Roubtsova , Honghong Zhang , Céline Caseys , Daniel J. Kliebenstein , Kyungnam Kim , Richard M. Bostock , Yong‐Hwan Lee , Martin B. Dickman , Doil Choi , Eunsook Park , Savithramma P. Dinesh‐Kumar
|
| Journal Info |
Nature Portfolio | Nature Communications , vol: 15
, iss: 1
|
| Publication Date |
2/29/2024 |
| ISSN |
2041-1723 |
Type |
article |
| Open Access |
gold
|
| DOI |
https://doi.org/10.1038/s41467-024-45839-2 |
| Keywords |
Pathogenicity (Score: 0.474932)
|
