title: Enhancement of fludioxonil fungicidal activity by disrupting cellular glutathione homeostasis with 2,5-dihydroxybenzoic acid.
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.
authors.affiliation: Plant Mycotoxin Research Unit, Western Regional Research Center, USDA-ARS, Albany, CA 94710, USA.
authors.forename: Jong H
authors.initials: JH
authors.lastname: Kim
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Campbell
authors.forename: Noreen
authors.initials: N
authors.lastname: Mahoney
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Chan
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Molyneux
authors.forename: Gregory S
authors.initials: GS
authors.lastname: May
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001231:Aspergillus flavus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D001241:Aspirin / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology*; D004357:Drug Synergism; D005841:Gentisates / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011758:Pyrroles / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D004149:Dioxoles; D005841:Gentisates; D011758:Pyrroles; D020928:Mitogen-Activated Protein Kinases; C108339:fludioxonil; D005978:Glutathione; D001241:Aspirin; C010925:2,5-dihydroxybenzoic acid