Calcineurin, Mpk1 and Hog1 MAPK pathways independently control fludioxonil antifungal sensitivity in Cryptococcus neoformans

Microbiology
Kaihei KojimaJoseph Heitman

Abstract

Fludioxonil is employed as an agricultural fungicide to control plant-pathogenic fungi such as Botrytis cinerea. Cryptococcus neoformans is a basidiomycetous human fungal pathogen that causes fatal disease in immunocompromised hosts. This paper demonstrates that three different signalling cascades regulate sensitivity of C. neoformans to fludioxonil. Fludioxonil inhibited growth of the serotype A sequence reference strain H99 but not that of the sequenced serotype D strain JEC21. In the drug-sensitive wild-type strain, fludioxonil exposure activated the Hog1 osmosensing pathway, and hog1Delta mutations conferred fludioxonil resistance. Fludioxonil treatment caused cell growth inhibition following cell swelling and cytokinesis defects in the sensitive wild-type but not in a hog1Delta mutant strain, suggesting that Hog1 activation results in morphological cellular defects. Fludioxonil exerted a fungistatic effect on the wild-type strain H99, but exhibited fungicidal activity against calcineurin mutant strains, indicating that the calcineurin pathway contributes to drug resistance in this fungus. Combination of fludioxonil and the calcineurin inhibitor FK506 synergistically inhibited C. neoformans growth. mpk1Delta MAPK mutant str...Continue Reading

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Citations

Jan 12, 2008·Current Genetics·Carla J EatonBarry Scott
Dec 16, 2006·Nature Reviews. Microbiology·Yong-Sun BahnMaria E Cardenas
May 17, 2007·Nature Reviews. Microbiology·William J SteinbachJoseph Heitman
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Sep 1, 2007·Molecular Plant Pathology·Brian WilliamsonJan A L van Kan
Jan 8, 2016·Biotechnology, Biotechnological Equipment·Hasan Karadag, Fadil Ozhan

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