Discovery of broad-spectrum fungicides that block septin-dependent infection processes of pathogenic fungi
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Many pathogenic fungi depend on the development of specialized infection structures called appressoria to invade their hosts and cause disease. Impairing the function of fungal infection structures therefore provides a potential means by which diseases could be prevented. In spite of this extraordinary potential, however, relatively few anti-penetrant drugs have been developed to control fungal diseases, of either plants or animals. In the present study, we report the identification of compounds that act specifically to prevent fungal infection. We found that the organization of septin GTPases, which are essential for appressorium-mediated infection in the rice blast fungus Magnaporthe oryzae, requires very-long-chain fatty acids (VLCFAs), which act as mediators of septin organization at membrane interfaces. VLCFAs promote septin recruitment to curved plasma membranes and depletion of VLCFAs prevents septin assembly and host penetration by M. oryzae. We observed that VLCFA biosynthesis inhibitors not only prevent rice blast disease, but also show effective, broad-spectrum fungicidal activity against a wide range of fungal pathogens of maize, wheat and locusts, without affecting their respective hosts. Our findings reveal a mechanism underlying septin-mediated infection structure formation in fungi and provide a class of fungicides to control diverse diseases of plants and animals.
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Magnaporthe oryzae depends on VLCFAs for pathogenicity.
“not only viruses but also the rice blast fungus Magnaporthe oryzae seem to depend on VLCFAs for pathogenicity48.”
From Peroxisomal very long-chain fatty acid transport is targeted by herpesviruses and the antiviral host response (2022) · cites this paper as [48]
The fungus uses VLCFAs to recruit filament-forming septins to curved plasma membranes, promoting formation of a penetration peg required for host infection.
“He and co-workers show that the fungus uses VLCFAs to recruit filament-forming septins to curved plasma membranes, thereby promoting the formation of a penetration peg required for host infection.”
From Peroxisomal very long-chain fatty acid transport is targeted by herpesviruses and the antiviral host response (2022) · cites this paper as [48]
Melanin accumulation defects inhibit penetration peg formation, preventing pathogens from breaching host defense barriers and impairing pathogenicity.
“Concurrently, melanin accumulation defects inhibit penetration peg formation. As the key structure for penetrating host tissue, peg formation failure directly prevents pathogens from breaching host defense barriers. This impedes successful tissue invasion and ultimately impairs pathogenicity [51].”
From Fungal Melanin in Plant Pathogens: Complex Biosynthesis Pathways and Diverse Biological Functions (2025) · cites this paper as [51]
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- Authors
- He, M., Su, J., Xu, Y., Chen, J., Chern, M., Lei, M., Qi, T., Wang, Z., Ryder, L. S., Tang, B., Osés-Ruiz, M., Zhu, K., Cao, Y., Yan, X., Eisermann, I., Luo, Y., Li, W., Wang, J., Yin, J., Lam, S. M., Peng, G., Sun, X., Zhu, X., Ma, B., Wang, J., Liu, J., Qing, H., Song, L., Wang, L., Hou, Q., Qin, P., Li, Y., Fan, J., Li, D., Wang, Y., Wang, X., Jiang, L., Shui, G., Xia, Y., Gong, G., Huang, F., Wang, W., Wu, X., Li, P., Zhu, L., Li, S., Talbot, N. J., & Chen, X.
- Affiliations
- Sichuan Agricultural University (CN)
- China West Normal University (CN)
- University of California, Davis (US)
- Nanjing Agricultural University (CN)
- Norwich Research Park (GB)
- Chinese Academy of Sciences (CN)
- Chongqing University (CN)
- Corresponding author
- Chen, Xuewei
- ORCID
- He, Min
- Chen, Jinhua
- Chern, Mawsheng
- Qi, Tuo
- Wang, Zongkuan
- Ryder, Lauren S.
- Tang, Bozeng
- Osés-Ruiz, Míriam
- Zhu, Keke
- Yan, Xia
- Eisermann, Iris
- Li, Weitao
- Wang, Jing
- Yin, Junjie
- Lam, Sin Man
- Peng, Guoxiong
- Sun, Xiaofang
- Zhu, Xiaobo
- Ma, Bingtian
- Wang, Jichun
- Wang, Long
- Hou, Qingqing
- Li, Yan
- Fan, Jing
- Wang, Yuping
- Wang, Xiue
- Jiang, Ling
- Shui, Guanghou
- Xia, Yuxian
- Gong, Guoshu
- Huang, Fu
- Wang, Wenming
- Li, Ping
- Zhu, Lihuang
- Li, Shigui
- Talbot, Nicholas J.
- Chen, Xuewei
- Venue
- Nature Microbiology
- Published
- 2020-09-21
- Volume
- 5
- Issue
- 12
- Pages
- 1565-1575
- ISSN
- 2058-5276 (ISSN-L)
- OpenAlex
- W3087047077
- Cited by
- 86
- References
- 56
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 23 · 2023: 13 · 2022: 17 · 2021: 6 · 2020: 1 · 2012: 1
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Nature Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Academica-e (Universidad Pública de Navarra) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/N009959/1, BB/N009959/2, BBS/E/J/000PR9797)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- septins, appressoria, Magnaporthe oryzae, rice blast, very long chain fatty acids, fungal infection, host penetration, broad-spectrum fungicide, plant pathogenic fungi
- MeSH terms
- Ascomycota, Enzyme Inhibitors, Fatty Acids, Fungal Proteins, Fungi, Fungicides, Industrial, Plant Diseases, Oryza, Septins
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