Sub-telomere directed gene expression during initiation of invasive aspergillosis.

Aspergillus fumigatus is a common mould whose spores are a component of the normal airborne flora. Immune dysfunction permits developmental growth of inhaled spores in the human lung causing aspergillosis, a significant threat to human health in the form of allergic, and life-threatening invasive in...

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Autores principales:	Andrew McDonagh, Natalie D Fedorova, Jonathan Crabtree, Yan Yu, Stanley Kim, Dan Chen, Omar Loss, Timothy Cairns, Gustavo Goldman, Darius Armstrong-James, Ken Haynes, Hubertus Haas, Markus Schrettl, Gregory May, William C Nierman, Elaine Bignell
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8102d0436da64919bd20474d8920d4bb
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spelling	oai:doaj.org-article:8102d0436da64919bd20474d8920d4bb2021-11-25T05:47:28ZSub-telomere directed gene expression during initiation of invasive aspergillosis.1553-73661553-737410.1371/journal.ppat.1000154https://doaj.org/article/8102d0436da64919bd20474d8920d4bb2008-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18787699/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Aspergillus fumigatus is a common mould whose spores are a component of the normal airborne flora. Immune dysfunction permits developmental growth of inhaled spores in the human lung causing aspergillosis, a significant threat to human health in the form of allergic, and life-threatening invasive infections. The success of A. fumigatus as a pathogen is unique among close phylogenetic relatives and is poorly characterised at the molecular level. Recent genome sequencing of several Aspergillus species provides an exceptional opportunity to analyse fungal virulence attributes within a genomic and evolutionary context. To identify genes preferentially expressed during adaptation to the mammalian host niche, we generated multiple gene expression profiles from minute samplings of A. fumigatus germlings during initiation of murine infection. They reveal a highly co-ordinated A. fumigatus gene expression programme, governing metabolic and physiological adaptation, which allows the organism to prosper within the mammalian niche. As functions of phylogenetic conservation and genetic locus, 28% and 30%, respectively, of the A. fumigatus subtelomeric and lineage-specific gene repertoires are induced relative to laboratory culture, and physically clustered genes including loci directing pseurotin, gliotoxin and siderophore biosyntheses are a prominent feature. Locationally biased A. fumigatus gene expression is not prompted by in vitro iron limitation, acid, alkaline, anaerobic or oxidative stress. However, subtelomeric gene expression is favoured following ex vivo neutrophil exposure and in comparative analyses of richly and poorly nourished laboratory cultured germlings. We found remarkable concordance between the A. fumigatus host-adaptation transcriptome and those resulting from in vitro iron depletion, alkaline shift, nitrogen starvation and loss of the methyltransferase LaeA. This first transcriptional snapshot of a fungal genome during initiation of mammalian infection provides the global perspective required to direct much-needed diagnostic and therapeutic strategies and reveals genome organisation and subtelomeric diversity as potential driving forces in the evolution of pathogenicity in the genus Aspergillus.Andrew McDonaghNatalie D FedorovaJonathan CrabtreeYan YuStanley KimDan ChenOmar LossTimothy CairnsGustavo GoldmanDarius Armstrong-JamesKen HaynesHubertus HaasMarkus SchrettlGregory MayWilliam C NiermanElaine BignellPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 9, p e1000154 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Andrew McDonagh Natalie D Fedorova Jonathan Crabtree Yan Yu Stanley Kim Dan Chen Omar Loss Timothy Cairns Gustavo Goldman Darius Armstrong-James Ken Haynes Hubertus Haas Markus Schrettl Gregory May William C Nierman Elaine Bignell Sub-telomere directed gene expression during initiation of invasive aspergillosis.
description	Aspergillus fumigatus is a common mould whose spores are a component of the normal airborne flora. Immune dysfunction permits developmental growth of inhaled spores in the human lung causing aspergillosis, a significant threat to human health in the form of allergic, and life-threatening invasive infections. The success of A. fumigatus as a pathogen is unique among close phylogenetic relatives and is poorly characterised at the molecular level. Recent genome sequencing of several Aspergillus species provides an exceptional opportunity to analyse fungal virulence attributes within a genomic and evolutionary context. To identify genes preferentially expressed during adaptation to the mammalian host niche, we generated multiple gene expression profiles from minute samplings of A. fumigatus germlings during initiation of murine infection. They reveal a highly co-ordinated A. fumigatus gene expression programme, governing metabolic and physiological adaptation, which allows the organism to prosper within the mammalian niche. As functions of phylogenetic conservation and genetic locus, 28% and 30%, respectively, of the A. fumigatus subtelomeric and lineage-specific gene repertoires are induced relative to laboratory culture, and physically clustered genes including loci directing pseurotin, gliotoxin and siderophore biosyntheses are a prominent feature. Locationally biased A. fumigatus gene expression is not prompted by in vitro iron limitation, acid, alkaline, anaerobic or oxidative stress. However, subtelomeric gene expression is favoured following ex vivo neutrophil exposure and in comparative analyses of richly and poorly nourished laboratory cultured germlings. We found remarkable concordance between the A. fumigatus host-adaptation transcriptome and those resulting from in vitro iron depletion, alkaline shift, nitrogen starvation and loss of the methyltransferase LaeA. This first transcriptional snapshot of a fungal genome during initiation of mammalian infection provides the global perspective required to direct much-needed diagnostic and therapeutic strategies and reveals genome organisation and subtelomeric diversity as potential driving forces in the evolution of pathogenicity in the genus Aspergillus.
format	article
author	Andrew McDonagh Natalie D Fedorova Jonathan Crabtree Yan Yu Stanley Kim Dan Chen Omar Loss Timothy Cairns Gustavo Goldman Darius Armstrong-James Ken Haynes Hubertus Haas Markus Schrettl Gregory May William C Nierman Elaine Bignell
author_facet	Andrew McDonagh Natalie D Fedorova Jonathan Crabtree Yan Yu Stanley Kim Dan Chen Omar Loss Timothy Cairns Gustavo Goldman Darius Armstrong-James Ken Haynes Hubertus Haas Markus Schrettl Gregory May William C Nierman Elaine Bignell
author_sort	Andrew McDonagh
title	Sub-telomere directed gene expression during initiation of invasive aspergillosis.
title_short	Sub-telomere directed gene expression during initiation of invasive aspergillosis.
title_full	Sub-telomere directed gene expression during initiation of invasive aspergillosis.
title_fullStr	Sub-telomere directed gene expression during initiation of invasive aspergillosis.
title_full_unstemmed	Sub-telomere directed gene expression during initiation of invasive aspergillosis.
title_sort	sub-telomere directed gene expression during initiation of invasive aspergillosis.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/8102d0436da64919bd20474d8920d4bb
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Sub-telomere directed gene expression during initiation of invasive aspergillosis.

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