Fungicide activity through activation of a fungal signalling pathway

Kaihei Kojima, Yoshitaka Takano, Akira Yoshimi, Chihiro Tanaka, Taisei Kikuchi, Tetsuro Okuno

Research output: Contribution to journalArticlepeer-review

183 Citations (Scopus)


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 (MARK) related to yeast Hog1, was isolated from the fungal pathogen ColletoMchum 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 MARK 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 Oscl. Furthermore, fludioxonil activates Hog1-type MAPKs in the plant pathogenic fungi Cochliobolus heterostrophus and Botrytis cineres. These results strongly suggest that fludioxonil acts as a fungicide, in part, through activation of the MAPK cascade in fungal pathogens.

Original languageEnglish
Pages (from-to)1785-1796
Number of pages12
JournalMolecular Microbiology
Issue number6
Publication statusPublished - 2004 Sep

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


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