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Resistance risk assessment and molecular basis of phenamacril in Fusarium pseudograminearum
Bingxue Zhang1, Kai He1, Wenfeng Zhang1
1Department of Plant Protection, College of Horticulture and Plant Protection, Henan University of Science and Technology, Luoyang 471023, China; Henan Engineering Technology Research Center of Green Plant Protection, Luoyang 471023, China.
Abstract:
The fungicide phenamacril, which acts as a cyanoacrylate fungicide that targets myosin function, exhibits strong inhibitory activity against Fusarium pseudograminearum. However, the underlying resistance mechanisms and the potential risk of resistance development in this pathogen to phenamacril have not yet been fully evaluated. This study determined the sensitivity of 208 strains from Henan Province to phenamacril, with a mean EC50 of 0.2339 ± 0.0496 μg/mL. Three stably inherited mutants (Y625F, D540G and S217L) were obtained through laboratory resistance evolution, but they exhibited defects in temperature stress tolerance, spore germination, pathogenicity, and toxin synthesis. No cross-resistance was observed between phenamacril and carbendazim, prochloraz, epoxiconazole, fluazinam, fludioxonil, and pydiflumetofen. In addition, phenamacril treatment significantly upregulated the expression of FpMyosin-5 in resistant mutants. Molecular docking and dynamics simulations further revealed that these mutations in FpMyosin-5 all reduced their binding affinity for phenamacril compared to the wild-type. Altogether, these results provide more evidence that phenamacril inhibits F. pseudograminearum by targeting the FpMyosin-5 protein, which contributes to managing phenamacril resistance in Fusarium crown rot.
Insights
Phenamacril effectively inhibits Fusarium pseudograminearum by targeting FpMyosin-5. Laboratory evolution yielded resistant mutants with reduced fitness, suggesting low resistance risk for this fungicide in managing Fusarium crown rot.
Area of Science:
- Agricultural Science
- Mycology
- Biochemistry
Background:
- Phenamacril is a cyanoacrylate fungicide targeting myosin function with high efficacy against Fusarium pseudograminearum.
- Understanding phenamacril resistance mechanisms in F. pseudograminearum is crucial for sustainable disease management.
Purpose of the Study:
- To evaluate the sensitivity of F. pseudograminearum strains to phenamacril.
- To investigate the mechanisms of phenamacril resistance and assess cross-resistance potential.
- To elucidate the molecular interactions between phenamacril and its target protein.
Main Methods:
- Sensitivity testing of 208 F. pseudograminearum strains.
- Laboratory-induced resistance evolution and characterization of mutants.
- Analysis of cross-resistance with existing fungicides.
- Gene expression analysis and molecular docking/dynamics simulations of FpMyosin-5.
Main Results:
- A mean EC50 of 0.2339 ± 0.0496 μg/mL was determined for phenamacril.
- Three resistant mutants (Y625F, D540G, S217L) showed reduced fitness (temperature tolerance, germination, pathogenicity, toxin synthesis).
- No cross-resistance was observed with six common fungicides; phenamacril upregulated FpMyosin-5 expression, and mutations decreased binding affinity.
Conclusions:
- Phenamacril inhibits F. pseudograminearum by targeting the FpMyosin-5 protein.
- Mutations conferring resistance reduce pathogen fitness, indicating a low risk of resistance development.
- Findings support phenamacril's role in managing Fusarium crown rot and fungicide resistance strategies.
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