Comprehensive analysis of the mechanisms conferring resistance to phenamacril in the Fusarium species

Author: mycolabadmin
2/11/2025
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Summary

Fusarium fungi cause serious diseases in crops like wheat, corn, and fruits, causing huge losses in agriculture worldwide. Phenamacril is a new antifungal drug designed specifically to fight these fungi by blocking a protein they need to grow. However, the fungi are developing resistance to this drug through genetic mutations and other biological mechanisms, making it less effective over time. Understanding how this resistance develops helps scientists develop better strategies to maintain the drug’s effectiveness and protect our food supply.

Background

Fusarium species are destructive fungal pathogens causing catastrophic diseases in fruits, cereals, and vegetables worldwide, resulting in significant crop losses and contamination with mycotoxins. Phenamacril is a newly developed site-specific fungicide designed to target Fusarium species by inhibiting myosin-5, an essential protein for fungal growth and disease development. However, resistance to phenamacril has emerged in both field and laboratory settings, threatening the effectiveness of this fungicide.

Objective

To comprehensively analyze the molecular, genetic, and environmental mechanisms underlying Fusarium species resistance to phenamacril. This review examines the mechanisms of resistance development and emphasizes the importance of integrated approaches to monitoring and managing drug-resistant Fusarium populations.

Results

Mutations in the myosin-5 gene (FaMyo5) confer phenamacril resistance, with specific point mutations (K216R/E, S217P/L, E420K/G/D) providing strong resistance. ABC transporters and efflux pumps play critical roles in reducing intracellular phenamacril levels, while epigenetic modifications including DNA methylation, histone alterations, and non-coding RNA regulation also contribute to resistance development. Multiple Fusarium species show varying mutation patterns and resistance levels across different myosin protein domains.

Conclusion

Phenamacril resistance in Fusarium species is a complex phenomenon involving target protein alterations, ABC transporter-mediated efflux, and epigenetic mechanisms. Integrating monitoring strategies, developing efflux pump inhibitors, alternating fungicides with different modes of action, and implementing integrated pest management approaches are essential for sustainable disease control. Continued research on resistance mechanisms and development of novel fungicides are critical for maintaining the effectiveness of phenamacril and ensuring global food security.

Published in:Frontiers in Cellular and Infection Microbiology,
Study Type:Review,
Source: PMID: 40007612, doi: 10.3389/fcimb.2025.1536532