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Mon1 Is Essential for Fungal Virulence and Stress Survival in Cryptococcus neoformans.

ABSTRACT: Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Saccharomyces cerevisiae Mon1, in a human fungal pathogen, Cryptococcus neoformans. Mutation in mon1 resulted in hypersensitivity to thermal stress. The mon1 deletion mutant exhibited increased sensitivity to cell wall and endoplasmic reticulum stress. However, the mon1 deletion mutant showed more resistance to the antifungal agent fluconazole. In vivo studies demonstrated that compared to the wild-type strain, the mon1 deletion mutant attenuated virulence in the Galleria mellonella insect model. Moreover, the mon1 deletion mutant was avirulent in the murine inhalation model. These results demonstrate that Mon1 plays a crucial role in stress survival and pathogenicity in C. neoformans.

SUBMITTER: Son YE

PROVIDER: S-EPMC6023253 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Mon1 Is Essential for Fungal Virulence and Stress Survival in Cryptococcus neoformans.

Son Ye-Eun YE Jung Won-Hee WH Oh Sang-Hun SH Kwak Jin-Hwan JH Cardenas Maria E ME Park Hee-Soo HS

Mycobiology 20180521 2

Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Saccharomyces cerevisiae Mon1, in a human fungal pathogen, Cryptococcus neoformans. Mutation in mon1 resulted in hypersensitivity to thermal stress. The mon1 deletion mutant exhibited increased sensitivity to cell wall and endopl ...[more]

PMID: 29963312

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