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A small molecule species specifically inhibits Fusarium myosin I
Chengqi Zhang1, Yun Chen1, Yanni Yin1
1Institute of Biotechnology, Zhejiang University, Hangzhou, 310058, China.
Abstract:
Fusarium head blight (FHB) caused by Fusarium graminearum is a devastating disease of cereal crops worldwide. Recently, a novel fungicide JS399-19 has been launched into the marketplace to manage FHB. It is compelling that JS399-19 shows highly inhibitory activity towards some Fusarium species, but not to other fungi, indicating that it is an environmentally compatible fungicide. To explore the mode of action of this species-specific compound, we conducted a whole-genome transcript profiling together with genetic and biochemical assays, and discovered that JS399-19 targets the myosin I of F. graminearum (FgMyo1). FgMyo1 is essential for F. graminearum growth. A point mutation S217L or E420K in FgMyo1 is responsible for F. graminearum resistance to JS399-19. In addition, transformation of F. graminearum with the myosin I gene of Magnaporthe grisea, the causal agent of rice blast, also led to JS399-19 resistance. JS399-19 strongly inhibits the ATPase activity of the wild-type FgMyo1, but not the mutated FgMyo1(S217L/E420K) . These results provide us a new insight into the design of species-specific antifungal compounds. Furthermore, our strategy can be applied to identify novel drug targets in various pathogenic organisms.
Insights
A new fungicide, JS399-19, targets a specific protein in Fusarium graminearum, offering effective control for Fusarium head blight (FHB) in crops. This species-specific action highlights its environmental compatibility and potential for novel antifungal drug development.
Area of Science:
- Agricultural Science
- Mycology
- Biochemistry
Background:
- Fusarium head blight (FHB), caused by Fusarium graminearum, is a significant global threat to cereal crops.
- A novel, environmentally compatible fungicide, JS399-19, demonstrates species-specific activity against certain Fusarium species.
Purpose of the Study:
- To elucidate the mode of action of the species-specific fungicide JS399-19.
- To identify the molecular target of JS399-19 in Fusarium graminearum.
Main Methods:
- Whole-genome transcript profiling was employed to analyze the fungicide's effects.
- Genetic assays, including gene transformation and point mutation analysis, were conducted.
- Biochemical assays assessed the impact of JS399-19 on enzyme activity.
Main Results:
- JS399-19 was identified to target myosin I of Fusarium graminearum (FgMyo1), a protein crucial for fungal growth.
- Specific point mutations (S217L or E420K) in FgMyo1 confer resistance to JS399-19.
- Transformation with myosin I from other fungi also induced resistance, confirming the target specificity.
- JS399-19 inhibits the ATPase activity of wild-type FgMyo1 but not the mutated forms.
Conclusions:
- The fungicide JS399-19 specifically targets FgMyo1, providing a new avenue for managing FHB.
- Understanding this species-specific mechanism aids in designing targeted antifungal agents.
- The employed strategy can be applied to discover novel drug targets in other pathogenic organisms.
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