Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>

ABSTRACT Cryptococcus neoformans is one of the few environmental fungi that can survive within a mammalian host and cause disease. Although many of the factors responsible for establishing virulence have been recognized, how they are expressed in response to certain host-derived cellular stresses is...

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Autores principales:	Jay Leipheimer, Amanda L. M. Bloom, Christopher S. Campomizzi, Yana Salei, John C. Panepinto
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Cryptococcus neoformans mRNA degradation mRNA stability oxidative stress stress response transcription factors Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/224be18819da421399e064fbf1534a9e
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spelling	oai:doaj.org-article:224be18819da421399e064fbf1534a9e2021-11-15T15:54:47ZTranslational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>10.1128/mBio.02143-192150-7511https://doaj.org/article/224be18819da421399e064fbf1534a9e2019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02143-19https://doaj.org/toc/2150-7511ABSTRACT Cryptococcus neoformans is one of the few environmental fungi that can survive within a mammalian host and cause disease. Although many of the factors responsible for establishing virulence have been recognized, how they are expressed in response to certain host-derived cellular stresses is rarely addressed. Here, we characterize the temporal translational response of C. neoformans to oxidative stress. We find that translation is largely inhibited through the phosphorylation of the critical initiation factor eIF2α (α subunit of eukaryotic initiation factor 2) by a sole kinase. Preventing eIF2α-mediated translational suppression resulted in growth sensitivity to hydrogen peroxide (H2O2). Our work suggests that translational repression in response to H2O2 partly facilitates oxidative stress adaptation by accelerating the decay of abundant non-stress-related transcripts while facilitating the proper expression levels of select oxidative stress response factors. Our results illustrate translational suppression as a critical determinant of select mRNA decay, gene expression, and subsequent survival in response to oxidative stress. IMPORTANCE Fungal survival in a mammalian host requires the coordinated expression and downregulation of a large cohort of genes in response to cellular stresses. Initial infection with C. neoformans occurs in the lungs, where it interacts with host macrophages. Surviving macrophage-derived cellular stresses, such as the production of reactive oxygen and nitrogen species, is believed to promote dissemination into the central nervous system. Therefore, investigating how an oxidative stress-resistant phenotype is brought about in C. neoformans not only furthers our understanding of fungal pathogenesis but also unveils mechanisms of stress-induced gene reprogramming. We discovered that H2O2-derived oxidative stress resulted in severe translational suppression and that this suppression was necessary for the accelerated decay and expression of tested transcripts.Jay LeipheimerAmanda L. M. BloomChristopher S. CampomizziYana SaleiJohn C. PanepintoAmerican Society for MicrobiologyarticleCryptococcus neoformansmRNA degradationmRNA stabilityoxidative stressstress responsetranscription factorsMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cryptococcus neoformans mRNA degradation mRNA stability oxidative stress stress response transcription factors Microbiology QR1-502
spellingShingle	Cryptococcus neoformans mRNA degradation mRNA stability oxidative stress stress response transcription factors Microbiology QR1-502 Jay Leipheimer Amanda L. M. Bloom Christopher S. Campomizzi Yana Salei John C. Panepinto Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
description	ABSTRACT Cryptococcus neoformans is one of the few environmental fungi that can survive within a mammalian host and cause disease. Although many of the factors responsible for establishing virulence have been recognized, how they are expressed in response to certain host-derived cellular stresses is rarely addressed. Here, we characterize the temporal translational response of C. neoformans to oxidative stress. We find that translation is largely inhibited through the phosphorylation of the critical initiation factor eIF2α (α subunit of eukaryotic initiation factor 2) by a sole kinase. Preventing eIF2α-mediated translational suppression resulted in growth sensitivity to hydrogen peroxide (H2O2). Our work suggests that translational repression in response to H2O2 partly facilitates oxidative stress adaptation by accelerating the decay of abundant non-stress-related transcripts while facilitating the proper expression levels of select oxidative stress response factors. Our results illustrate translational suppression as a critical determinant of select mRNA decay, gene expression, and subsequent survival in response to oxidative stress. IMPORTANCE Fungal survival in a mammalian host requires the coordinated expression and downregulation of a large cohort of genes in response to cellular stresses. Initial infection with C. neoformans occurs in the lungs, where it interacts with host macrophages. Surviving macrophage-derived cellular stresses, such as the production of reactive oxygen and nitrogen species, is believed to promote dissemination into the central nervous system. Therefore, investigating how an oxidative stress-resistant phenotype is brought about in C. neoformans not only furthers our understanding of fungal pathogenesis but also unveils mechanisms of stress-induced gene reprogramming. We discovered that H2O2-derived oxidative stress resulted in severe translational suppression and that this suppression was necessary for the accelerated decay and expression of tested transcripts.
format	article
author	Jay Leipheimer Amanda L. M. Bloom Christopher S. Campomizzi Yana Salei John C. Panepinto
author_facet	Jay Leipheimer Amanda L. M. Bloom Christopher S. Campomizzi Yana Salei John C. Panepinto
author_sort	Jay Leipheimer
title	Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_short	Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_full	Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_fullStr	Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_full_unstemmed	Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_sort	translational regulation promotes oxidative stress resistance in the human fungal pathogen <named-content content-type="genus-species">cryptococcus neoformans</named-content>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/224be18819da421399e064fbf1534a9e
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Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>

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