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.
Autophagy ; Cell Wall ; Cryptococcus neoformans* ; Cryptococcus* ; Endoplasmic Reticulum Stress ; Fluconazole ; GTP Phosphohydrolases ; Guanine Nucleotide Exchange Factors ; Humans ; Hypersensitivity ; Inhalation ; Insects ; Saccharomyces cerevisiae ; Vacuoles ; Virulence*

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Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 22 ; Chromosomes, Human, Pair 9 ; Female ; Fusion Proteins, bcr-abl/genetics ; Humans ; In Situ Hybridization, Fluorescence ; Karyotype ; Middle Aged ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/pathology ; Retinoblastoma Binding Proteins/genetics ; *Translocation, Genetic ; Ubiquitin-Protein Ligases/genetics