Role of an Expanded Inositol Transporter Repertoire in <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Sexual Reproduction and Virulence

ABSTRACT Cryptococcus neoformans and Cryptococcus gattii are globally distributed human fungal pathogens and the leading causes of fungal meningitis. Recent studies reveal that myo-inositol is an important factor for fungal sexual reproduction. That C. neoformans can utilize myo-inositol as a sole c...

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Autores principales:	Chaoyang Xue, Tongbao Liu, Lydia Chen, Wenjun Li, Iris Liu, James W. Kronstad, Andreas Seyfang, Joseph Heitman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2010
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a48bddfcb97046d0af3494182dd08f37
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spelling	oai:doaj.org-article:a48bddfcb97046d0af3494182dd08f372021-11-15T15:38:14ZRole of an Expanded Inositol Transporter Repertoire in <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Sexual Reproduction and Virulence10.1128/mBio.00084-102150-7511https://doaj.org/article/a48bddfcb97046d0af3494182dd08f372010-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00084-10https://doaj.org/toc/2150-7511ABSTRACT Cryptococcus neoformans and Cryptococcus gattii are globally distributed human fungal pathogens and the leading causes of fungal meningitis. Recent studies reveal that myo-inositol is an important factor for fungal sexual reproduction. That C. neoformans can utilize myo-inositol as a sole carbon source and the existence of abundant inositol in the human central nervous system suggest that inositol is important for Cryptococcus development and virulence. In accord with this central importance of inositol, an expanded myo-inositol transporter (ITR) gene family has been identified in Cryptococcus. This gene family contains two phylogenetically distinct groups, with a total of 10 or more members in C. neoformans and at least six members in the sibling species C. gattii. These inositol transporter genes are differentially expressed under inositol-inducing conditions based on quantitative real-time PCR analyses. Expression of ITR genes in a Saccharomyces cerevisiae itr1 itr2 mutant lacking inositol transport can complement the slow-growth phenotype of this strain, confirming that ITR genes are bona fide inositol transporters. Gene mutagenesis studies reveal that the Itr1 and Itr1A transporters are important for myo-inositol stimulation of mating and that functional redundancies among the myo-inositol transporters likely exist. Deletion of the inositol 1-phosphate synthase gene INO1 in an itr1 or itr1a mutant background compromised virulence in a murine inhalation model, indicating the importance of inositol sensing and acquisition for fungal infectivity. Our study provides a platform for further understanding the roles of inositol in fungal physiology and virulence. IMPORTANCE Cryptococcus neoformans is an AIDS-associated human fungal pathogen that causes over 1 million cases of meningitis annually and is the leading cause of fungal meningitis in immunosuppressed patients. The initial cryptococcal infection is caused predominantly via inhalation of sexual spores or desiccated yeast cells from the environment. How this fungus completes its sexual cycle and produces infectious spores in nature and why it frequently infects the central nervous system to cause fatal meningitis are critical questions that remain to be understood. In this study, we demonstrate that inositol acquisition is important not only for fungal sexual reproduction but also for fungal virulence. We identified an expanded inositol transporter gene family that contains over 10 members, important for both fungal sexual reproduction and virulence. Our work contributes to our understanding of how fungi respond to the environmental inositol availability and its impact on sexual reproduction and virulence.Chaoyang XueTongbao LiuLydia ChenWenjun LiIris LiuJames W. KronstadAndreas SeyfangJoseph HeitmanAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 1, Iss 1 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Chaoyang Xue Tongbao Liu Lydia Chen Wenjun Li Iris Liu James W. Kronstad Andreas Seyfang Joseph Heitman Role of an Expanded Inositol Transporter Repertoire in <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Sexual Reproduction and Virulence
description	ABSTRACT Cryptococcus neoformans and Cryptococcus gattii are globally distributed human fungal pathogens and the leading causes of fungal meningitis. Recent studies reveal that myo-inositol is an important factor for fungal sexual reproduction. That C. neoformans can utilize myo-inositol as a sole carbon source and the existence of abundant inositol in the human central nervous system suggest that inositol is important for Cryptococcus development and virulence. In accord with this central importance of inositol, an expanded myo-inositol transporter (ITR) gene family has been identified in Cryptococcus. This gene family contains two phylogenetically distinct groups, with a total of 10 or more members in C. neoformans and at least six members in the sibling species C. gattii. These inositol transporter genes are differentially expressed under inositol-inducing conditions based on quantitative real-time PCR analyses. Expression of ITR genes in a Saccharomyces cerevisiae itr1 itr2 mutant lacking inositol transport can complement the slow-growth phenotype of this strain, confirming that ITR genes are bona fide inositol transporters. Gene mutagenesis studies reveal that the Itr1 and Itr1A transporters are important for myo-inositol stimulation of mating and that functional redundancies among the myo-inositol transporters likely exist. Deletion of the inositol 1-phosphate synthase gene INO1 in an itr1 or itr1a mutant background compromised virulence in a murine inhalation model, indicating the importance of inositol sensing and acquisition for fungal infectivity. Our study provides a platform for further understanding the roles of inositol in fungal physiology and virulence. IMPORTANCE Cryptococcus neoformans is an AIDS-associated human fungal pathogen that causes over 1 million cases of meningitis annually and is the leading cause of fungal meningitis in immunosuppressed patients. The initial cryptococcal infection is caused predominantly via inhalation of sexual spores or desiccated yeast cells from the environment. How this fungus completes its sexual cycle and produces infectious spores in nature and why it frequently infects the central nervous system to cause fatal meningitis are critical questions that remain to be understood. In this study, we demonstrate that inositol acquisition is important not only for fungal sexual reproduction but also for fungal virulence. We identified an expanded inositol transporter gene family that contains over 10 members, important for both fungal sexual reproduction and virulence. Our work contributes to our understanding of how fungi respond to the environmental inositol availability and its impact on sexual reproduction and virulence.
format	article
author	Chaoyang Xue Tongbao Liu Lydia Chen Wenjun Li Iris Liu James W. Kronstad Andreas Seyfang Joseph Heitman
author_facet	Chaoyang Xue Tongbao Liu Lydia Chen Wenjun Li Iris Liu James W. Kronstad Andreas Seyfang Joseph Heitman
author_sort	Chaoyang Xue
title	Role of an Expanded Inositol Transporter Repertoire in <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Sexual Reproduction and Virulence
title_short	Role of an Expanded Inositol Transporter Repertoire in <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Sexual Reproduction and Virulence
title_full	Role of an Expanded Inositol Transporter Repertoire in <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Sexual Reproduction and Virulence
title_fullStr	Role of an Expanded Inositol Transporter Repertoire in <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Sexual Reproduction and Virulence
title_full_unstemmed	Role of an Expanded Inositol Transporter Repertoire in <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Sexual Reproduction and Virulence
title_sort	role of an expanded inositol transporter repertoire in <named-content content-type="genus-species">cryptococcus neoformans</named-content> sexual reproduction and virulence
publisher	American Society for Microbiology
publishDate	2010
url	https://doaj.org/article/a48bddfcb97046d0af3494182dd08f37
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Role of an Expanded Inositol Transporter Repertoire in <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Sexual Reproduction and Virulence

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