G462S: the key mutation driving resistance in Alternaria alternata

A study conducted at Huazhong Agricultural University China thoroughly investigated the molecular mechanisms underlying resistance to DMI (Demethylation Inhibitor) fungicides in an important fungal pathogen of sweet cherry. Alternaria alternata is responsible for diseases such as leaf spots and fruit rots, leading to significant losses both before and after harvest.

The intensive use of DMI fungicides represents a widely adopted control strategy; however, in recent years, a progressive reduction in sensitivity has been observed in field populations, making it essential to understand the genetic basis of this phenomenon.

The study is based on the analysis of 109 pathogen isolates collected from different cherry orchards in China between 2022 and 2023. Through fungicide sensitivity assays, the authors identified a clear distinction between sensitive and resistant isolates, with significantly higher mean effective concentration (EC50) values in resistant strains, confirming the presence of resistance capable of compromising the efficacy of plant protection treatments.

Gene analysis

The core of the investigation focuses on the AaCYP51 gene which encodes a key enzyme in fungal sterol metabolism and represents the primary target of DMI fungicides. Genetic analysis revealed a consistent point mutation, designated G462S located within the coding region of the gene, systematically associated with resistant isolates and suggesting a direct role in conferring resistance.

At the same time, multiple mutations were identified in the promoter region of the gene, which are involved in regulating its expression.

A particularly innovative aspect of the study lies in the functional distinction between these two types of mutations. Through reciprocal genetic transformation experiments, the authors demonstrated that the G462S mutation is not only sufficient to confer resistance to DMI fungicides, but also capable of inducing increased expression of the gene itself, highlighting a dual structural and regulatory role.

In contrast, mutations in the promoter region contribute exclusively to gene overexpression without directly affecting the resistance phenotype.

Biological implications

From a biological perspective, this dual mechanism represents a sophisticated example of evolutionary adaptation. Increased expression of AaCYP51 can partially compensate for the effect of the fungicide by increasing the amount of available enzyme, while the mutation in the coding sequence reduces the affinity of the fungicide for its target, making resistance particularly effective and difficult to manage with conventional strategies.

The practical implications of this study are highly relevant for resistance management in agricultural systems. The identification of the G462S mutation as a molecular marker enables the development of diagnostic tools for early detection of resistance in field populations, while understanding overexpression mechanisms supports more sustainable strategies such as fungicide rotation and optimized application rates.

Conclusions

Overall, the article makes a significant contribution to understanding the molecular processes driving the evolution of fungicide resistance in fungal pathogens, highlighting the importance of integrated approaches combining genetics, physiology, and agronomic management to effectively address resistance challenges in modern cropping systems.

Source: Hussain, M., Zeng, Z.-z., Yin, W.-X. and Luo, C.-X. (2026), Dual roles of the G462S mutation of AaCYP51 in regulating self-overexpression and DMI resistance in Alternaria alternata. Pest Manag Sci, 82: 2870-2881. https://doi.org/10.1002/ps.70414

Image source: Redagricola

Melissa Venturi
University of Bologna (IT)

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