Abstract
The activity of fludioxonil, a phenylpyrrole fungicide, is elevated by coapplication of the aspirin/salicylic acid metabolite, 2,5-dihydroxybenzoic acid (2,5-DHBA). Fludioxonil activity is potentiated through a mitogen-activated protein kinase (MAPK) pathway that regulates osmotic/oxidative stress-responses. 2,5-DHBA disrupts cellular GSH (reduced glutathione)/GSSG (oxidized glutathione) homeostasis, further stressing the oxidative stress-response system. This stress enhances fludioxonil activity. 2,5-DHBA treatment also prevents tolerance of MAPK mutants resistant to fludioxonil.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Antifungal Agents / pharmacology*
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Aspergillus flavus / drug effects
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Aspergillus flavus / genetics
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Aspergillus flavus / growth & development
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Aspergillus fumigatus / drug effects
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Aspergillus fumigatus / genetics
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Aspergillus fumigatus / growth & development
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Aspirin / pharmacology
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Dioxoles / pharmacology*
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Drug Synergism
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Gentisates / chemistry
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Gentisates / pharmacology*
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Glutathione / metabolism*
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Homeostasis / drug effects
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MAP Kinase Signaling System / drug effects
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Microbial Sensitivity Tests
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism
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Mutation
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Pyrroles / pharmacology*
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Structure-Activity Relationship
Substances
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Antifungal Agents
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Dioxoles
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Gentisates
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Pyrroles
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Mitogen-Activated Protein Kinases
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fludioxonil
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Glutathione
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Aspirin
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2,5-dihydroxybenzoic acid