title: Fungicide activity through activation of a fungal signalling pathway.
abstract: Fungicides generally inhibit enzymatic reactions involved in fungal cellular biosynthesis. Here we report, for the first time, an example of fungicidal effects through hyperactivation of a fungal signal transduction pathway. The OSC1 gene, encoding a MAP kinase (MAPK) related to yeast Hog1, was isolated from the fungal pathogen Colletotrichum lagenarium that causes cucumber anthracnose. The osc1 knockout mutants were sensitive to high osmotic stress and showed increased resistance to the fungicide fludioxonil, indicating that Osc1 is involved in responses to hyperosmotic stress and sensitivity to fludioxonil. The Osc1 MAPK is phosphorylated under high osmotic conditions, indicating activation of Osc1 by high osmotic stress. Importantly, fludioxonil treatment also activates phosphorylation of Osc1, suggesting that improper activation of Osc1 by fludioxonil has negative effects on fungal growth. In the presence of fludioxonil, the wild-type fungus was not able to infect the host plant because of a failure of appressorium-mediated penetration, whereas osc1 mutants successfully infected plants. Analysis using a OSC1-GFP fusion gene indicated that Osc1 is rapidly translocated to the nucleus in appressorial cells after the addition of fludioxonil, suggesting that fludioxonil impairs the function of infection structures by activation of Osc1. Furthermore, fludioxonil activates Hog1-type MAPKs in the plant pathogenic fungi Cochliobolus heterostrophus and Botrytis cinerea. These results strongly suggest that fludioxonil acts as a fungicide, in part, through activation of the MAPK cascade in fungal pathogens.
authors.affiliation: Laboratory of Plant Pathology, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
authors.forename: Kaihei
authors.initials: K
authors.lastname: Kojima
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Takano
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshimi
authors.forename: Chihiro
authors.initials: C
authors.lastname: Tanaka
authors.forename: Taisei
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Okuno
mesh_terms: D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology*; D020231:Colletotrichum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D018553:Cucumis sativus / Q000033:anatomy & histology / Q000382:microbiology; D004149:Dioxoles / Q000494:pharmacology*; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009997:Osmotic Pressure; D010935:Plant Diseases / Q000382:microbiology; D018515:Plant Leaves / Q000382:microbiology; D011758:Pyrroles / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D014882:Water-Electrolyte Balance
chemical_list: D000935:Antifungal Agents; D004149:Dioxoles; D005656:Fungal Proteins; D011758:Pyrroles; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; C108339:fludioxonil