Novel A576T or M626I substitutions in the HAMP₅ domain of histidine kinase FfOs1 alter ligand-binding pocket to mediate fludioxonil resistance in Fusarium falciforme.

Authors

Bin Chen, Yuan Hu, Xuanming Zheng, Shanqinxue Gao, Jiawei Li, Aiguo Gu, Song Yang, Changyang Chen, Xiushi Song, Wenyong Shao, Changjun Chen

Published in

Pesticide biochemistry and physiology. Volume 223. Pages 107273. Epub Jul 22, 2026.

Abstract

Fusarium falciforme, one of the predominant causal agents of Fusarium root rot (FRR), poses a severe threat to sustainable soybean production worldwide. Fludioxonil (Flu) exhibits high antifungal activity against F. falciforme. In this study, the baseline sensitivity of 60 wild-type isolates to Flu was determined to have a mean EC₅₀ of 0.0401 ± 0.0114 μg/mL, with a skewed distribution. Three Flu^HR mutants generated via in vitro repetitive exposure to Flu (mutation frequency: 0.6%) exhibited heritable Flu resistance. All Flu^HR mutants exhibited significantly reduced mycelial growth, conidiation, and pathogenicity. Sequence alignment results showed that two novel amino acid substitutions (FfOs1^A576T and FfOs1^M626I) were located in the highly conserved HAMP₅ domain, and independently conferred high-level Flu resistance (RF > 2000) as validated of genetic methods. Molecular docking results revealed that the binding affinities of Flu to FfOs1^A576T or FfOs1^M626I were significantly reduced compared with those of the corresponding FfOs1 from the Flu^S parental strain. Furthermore, no cross-resistance was observed between Flu and other fungicides with different modes of action. All the Flu^R mutants displayed pronounced hypersensitivity to osmotic stress agents and a significant reduction in intracellular glycerol accumulation. Collectively, this study is the first to identify two novel substitutions, A576T and M626I, in the HAMP₅ domain of FfOs1 that individually confer Flu resistance while substantially impairing asexual reproduction, virulence, and osmoregulatory capacity in F. falciforme.

PMID:
42697645
Bibliographic data and abstract were imported from PubMed on 05 Sep 2026.

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