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Sci Rep. 2017 Jun 22;7(1):4044. doi: 10.1038/s41598-017-04290-8.

A novel bZIP protein, Gsb1, is required for oxidative stress response, mating, and virulence in the human pathogen Cryptococcus neoformans.

Author information

1
Department of Life Science, Chung-Ang University, Seoul, 06974, Korea.
2
Center for Fungal Pathogenesis, Seoul National University, Seoul, 08826, Korea.
3
Department of Biotechnology, Center for Fungal Pathogenesis, Yonsei University, Seoul, 03722, Korea.
4
Department of Life Science, Chung-Ang University, Seoul, 06974, Korea. hyunkang@cau.ac.kr.

Abstract

The human pathogen Cryptococcus neoformans, which causes life-threatening meningoencephalitis in immunocompromised individuals, normally faces diverse stresses in the human host. Here, we report that a novel, basic, leucine-zipper (bZIP) protein, designated Gsb1 (general stress-related bZIP protein 1), is required for its normal growth and diverse stress responses. C. neoformans gsb1Δ mutants grew slowly even under non-stressed conditions and showed increased sensitivity to high or low temperatures. The hypersensitivity of gsb1Δ to oxidative and nitrosative stresses was reversed by addition of a ROS scavenger. RNA-Seq analysis during normal growth revealed increased expression of a number of genes involved in mitochondrial respiration and cell cycle, but decreased expression of several genes involved in the mating-pheromone-responsive MAPK signaling pathway. Accordingly, gsb1Δ showed defective mating and abnormal cell-cycle progression. Reflecting these pleiotropic phenotypes, gsb1Δ exhibited attenuated virulence in a murine model of cryptococcosis. Moreover, RNA-Seq analysis under oxidative stress revealed that several genes involved in ROS defense, cell-wall remodeling, and protein glycosylation were highly induced in the wild-type strain but not in gsb1Δ. Gsb1 localized exclusively in the nucleus in response to oxidative stress. In conclusion, Gsb1 is a key transcription factor modulating growth, stress responses, differentiation, and virulence in C. neoformans.

PMID:
28642475
PMCID:
PMC5481450
DOI:
10.1038/s41598-017-04290-8
[Indexed for MEDLINE]
Free PMC Article

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