ArticleScientific reports2019
Phenylpyrrole fungicides act on triosephosphate isomerase to induce methylglyoxal stress and alter hybrid histidine kinase activity.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 66 citations in OpenAlex.
- Conformational diversity in poly-HAMP arrays and its implications for signal transduction.Protein science : a publication of the Protein Society · 2026Article
- Hybrid histidine kinases shape the architecture of the high osmolarity glycerol (HOG) pathway: from Saccharomyces cerevisiae to the priority pathogen Aspergillus fumigatus and other filamentous fungi.FEMS microbiology reviews · 2026Review
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- Proteomic Changes inJournal of proteome research · 2025Article
- Metatranscriptomic response of deep ocean microbial populations to infusions of oil and/or synthetic chemical dispersant.Applied and environmental microbiology · 2024Article
- A Conservative Mutant Version of the Mrr1 Transcription Factor Correlates with Reduced Sensitivity to Fludioxonil inPathogens (Basel, Switzerland) · 2024Article
- An array of signal-specific MoYpd1 isoforms determines full virulence in the pathogenic fungus Magnaporthe oryzae.Communications biology · 2024Article
- Article
- Polypeptides TargetingJournal of fungi (Basel, Switzerland) · 2023Article
- Human Triosephosphate Isomerase Is a Potential Target in Cancer Due to Commonly Occurring Post-Translational Modifications.Molecules (Basel, Switzerland) · 2023Review
- Induced Expression ofMicroorganisms · 2023Article
- Phenotypic and Target-Directed Screening Yields New Acaricidal Alternatives for the Control of Ticks.Molecules (Basel, Switzerland) · 2022Article
- Detection ofMicroorganisms · 2022Article
- The Transcription Factor CsAtf1 Negatively Regulates the Cytochrome P450 GeneJournal of fungi (Basel, Switzerland) · 2022Article
- Exploring Potential Mechanisms of Fludioxonil Resistance inJournal of fungi (Basel, Switzerland) · 2022Article
- Article
- Cell Wall Integrity and Its Industrial Applications in Filamentous Fungi.Journal of fungi (Basel, Switzerland) · 2022Review
- The Role of Dimorphism Regulating Histidine Kinase (Drk1) in the Pathogenic FungusJournal of fungi (Basel, Switzerland) · 2021Article
- A Radical Reimagining of Fungal Two-Component Regulatory Systems.Trends in microbiology · 2021Review
- Distinct role of HAMP and HAMP-like linker domains in regulating the activity of Hik1p, a hybrid histidine kinase 3 from Magnaporthe oryzae.Molecular genetics and genomics : MGG · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Fludioxonil, a natural product of pyrrolnitrin, is a potent fungicide used on crops worldwide. Drug action requires the presence of a group III hybrid histidine kinase (HHK) and the high osmolarity glycerol (HOG) pathway. We have reported that the drug does not act directly on HHK, but triggers the conversion of the kinase to a phosphatase, which dephosphorylates Ypd1 to constitutively activate HOG signaling. Still, the direct drug target remains unknown and mode of action ill defined. Here, we heterologously expressed a group III HHK, dimorphism-regulating kinase 1 (Drk1) in Saccharomyces cerevisae to delineate fludioxonil's target and action. We show that the drug interferes with triosephosphate isomerase (TPI) causing release of methylglyoxal (MG). MG activates the group III HHK and thus the HOG pathway. Drug action involved Drk1 cysteine 392, as a C392S substitution increased drug resistance in vivo. Drug sensitivity was reversed by dimedone treatment, indicating Drk1 responds in vivo to an aldehydic stress. Fludioxonil treatment triggered elevated cytosolic methylglyoxal. Likewise, methylglyoxal treatment of Drk1-expressing yeast phenocopied treatment with fludioxonil. Fludioxonil directly inhibited TPI and also caused it to release methylglyoxal in vitro. Thus, TPI is a drug target of the phenylpyrrole class of fungicides, inducing elevated MG which alters HHK activity, likely converting the kinase to a phosphatase that acts on Ypd1 to trigger HOG pathway activation and fungal cell death.
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