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

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posted on 02.04.2019 by Ye-Eun Son, Won-Hee Jung, Sang-Hun Oh, Jin-Hwan Kwak, Maria E. Cardenas, Hee-Soo Park

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.

Funding

The work at Kyungpook National University was supported by the Brain Korea 21 Plus Project funded by the Ministry of Education, Korea. The work at Duke University was supported by the NIH/NCI R01 CA154499 grant awarded to MEC.

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