NDLI: Sub-Telomere Directed Gene Expression during Initiation of InvasiveAspergillosis

Content Provider	PubMed Central
Author	Mcdonagh, Andrew Fedorova, Natalie D. Crabtree, Jonathan Yu, Yan Kim, Stanley Chen, Dan Loss, Omar Cairns, Timothy Goldman, Gustavo Darius, Armstrong-james Haynes, Ken Haas, Hubertus Markus, Schrettl May, Gregory Nierman, William C. Bignell, Elaine
Editor	Cormack, Brendan P.
Copyright Year	2008
Abstract	Aspergillus fumigatus is a common mould whose spores are acomponent of the normal airborne flora. Immune dysfunction permits developmentalgrowth of inhaled spores in the human lung causing aspergillosis, a significantthreat to human health in the form of allergic, and life-threatening invasiveinfections. The success of A. fumigatus as a pathogen is uniqueamong close phylogenetic relatives and is poorly characterised at the molecularlevel. Recent genome sequencing of several Aspergillus speciesprovides an exceptional opportunity to analyse fungal virulence attributeswithin a genomic and evolutionary context. To identify genes preferentiallyexpressed during adaptation to the mammalian host niche, we generated multiplegene expression profiles from minute samplings of A. fumigatusgermlings during initiation of murine infection. They reveal a highlyco-ordinated A. fumigatus gene expression programme, governingmetabolic and physiological adaptation, which allows the organism to prosperwithin the mammalian niche. As functions of phylogenetic conservation andgenetic locus, 28% and 30%, respectively, of theA. fumigatus subtelomeric and lineage-specific generepertoires are induced relative to laboratory culture, and physically clusteredgenes including loci directing pseurotin, gliotoxin and siderophore biosynthesesare a prominent feature. Locationally biased A. fumigatus geneexpression is not prompted by in vitro iron limitation, acid,alkaline, anaerobic or oxidative stress. However, subtelomeric gene expressionis favoured following ex vivo neutrophil exposure and incomparative analyses of richly and poorly nourished laboratory culturedgermlings. We found remarkable concordance between the A.fumigatus host-adaptation transcriptome and those resulting fromin vitro iron depletion, alkaline shift, nitrogenstarvation and loss of the methyltransferase LaeA. This first transcriptionalsnapshot of a fungal genome during initiation of mammalian infection providesthe global perspective required to direct much-needed diagnostic and therapeuticstrategies and reveals genome organisation and subtelomeric diversity aspotential driving forces in the evolution of pathogenicity in the genusAspergillus.
Related Links	http://dx.doi.org/10.1371/journal.ppat.1000154
Starting Page	1000154
File Format	PDF
ISSN	15537374
e-ISSN	15537374
Journal	PLoS Pathogens
Issue Number	9
Volume Number	4
Language	English
Publisher	Public Library of Science
Publisher Date	2008-09-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Immunology Genetics Molecular Biology Microbiology Parasitology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Virology Molecular Biology Parasitology Immunology Microbiology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
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9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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