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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-09-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000154&type=printable |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-8102d0436da64919bd20474d8920d4bb |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2008-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-8102d0436da64919bd20474d8920d4bb2025-08-20T02:17:29ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742008-09-0149e100015410.1371/journal.ppat.1000154Sub-telomere directed gene expression during initiation of invasive aspergillosis.Andrew McDonaghNatalie D FedorovaJonathan CrabtreeYan YuStanley KimDan ChenOmar LossTimothy CairnsGustavo GoldmanDarius Armstrong-JamesKen HaynesHubertus HaasMarkus SchrettlGregory MayWilliam C NiermanElaine BignellAspergillus 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000154&type=printable |
| spellingShingle | 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. PLoS Pathogens |
| title | 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_short | Sub-telomere directed gene expression during initiation of invasive aspergillosis. |
| title_sort | sub telomere directed gene expression during initiation of invasive aspergillosis |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000154&type=printable |
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