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

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...

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Autores principales:	Seon Ah Cheon, Eun Jung Thak, Yong-Sun Bahn, Hyun Ah Kang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/44bc26b80d794b11aa078c1b929a51ce
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spelling	oai:doaj.org-article:44bc26b80d794b11aa078c1b929a51ce2021-12-02T11:40:43ZA novel bZIP protein, Gsb1, is required for oxidative stress response, mating, and virulence in the human pathogen Cryptococcus neoformans10.1038/s41598-017-04290-82045-2322https://doaj.org/article/44bc26b80d794b11aa078c1b929a51ce2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04290-8https://doaj.org/toc/2045-2322Abstract 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.Seon Ah CheonEun Jung ThakYong-Sun BahnHyun Ah KangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seon Ah Cheon Eun Jung Thak Yong-Sun Bahn Hyun Ah Kang A novel bZIP protein, Gsb1, is required for oxidative stress response, mating, and virulence in the human pathogen Cryptococcus neoformans
description	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.
format	article
author	Seon Ah Cheon Eun Jung Thak Yong-Sun Bahn Hyun Ah Kang
author_facet	Seon Ah Cheon Eun Jung Thak Yong-Sun Bahn Hyun Ah Kang
author_sort	Seon Ah Cheon
title	A novel bZIP protein, Gsb1, is required for oxidative stress response, mating, and virulence in the human pathogen Cryptococcus neoformans
title_short	A novel bZIP protein, Gsb1, is required for oxidative stress response, mating, and virulence in the human pathogen Cryptococcus neoformans
title_full	A novel bZIP protein, Gsb1, is required for oxidative stress response, mating, and virulence in the human pathogen Cryptococcus neoformans
title_fullStr	A novel bZIP protein, Gsb1, is required for oxidative stress response, mating, and virulence in the human pathogen Cryptococcus neoformans
title_full_unstemmed	A novel bZIP protein, Gsb1, is required for oxidative stress response, mating, and virulence in the human pathogen Cryptococcus neoformans
title_sort	novel bzip protein, gsb1, is required for oxidative stress response, mating, and virulence in the human pathogen cryptococcus neoformans
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/44bc26b80d794b11aa078c1b929a51ce
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A novel bZIP protein, Gsb1, is required for oxidative stress response, mating, and virulence in the human pathogen Cryptococcus neoformans

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