Ubiquitous, Essential ... but Deadly
The genome sequence of the most common mould that causes disease worldwide is published in Nature on Thursday 22 December 2005. The code of Aspergillus fumigatus, an air-borne, soil-dwelling fungus, was cracked by an international team led by researchers from the Wellcome Trust Sanger Institute, The Institute for Genomic Research and the University of Manchester.
Although Aspergillus is most often harmless, it is an ‘opportunistic’ pathogen and is a leading cause of death in bone marrow transplant patients, HIV/AIDS patients and others whose immune system is compromised. The team identified a set of genes that are likely to be important for the disease-causing properties of Aspergillus and will be the first targets in the search for new treatments.
The genome of nearly 30 million base-pairs contains almost 10,000 genes. Before the sequencing project, fewer than 60 complete Aspergillus genes had been cloned and analysed. The Wellcome Trust Sanger Institute carried out half of the sequencing and was a major contributor to the genome analysis.
“We have discovered a treasure trove of new and important genes in Aspergillus.
“Our careful study and comparison with other closely related fungi provides researchers with a complete set of tools to work towards new treatments. We need to keep research aimed at unravelling the tricks used by all pathogens to inflict damage on us. The genome is a huge step in that direction.”
Dr Arnab Pain Lead author at the Wellcome Trust Sanger Institute
Fungal infections can be very difficult to treat and Aspergillus is the most common fungal species in critical care, such as transplants, leukaemia and HIV/AIDS. It is estimated that invasive infection by A. fumigatus occurs in 10 to 25 per cent of all leukaemia patients.
The team used the sequence to describe the full catalogues for three types of cell function that might be important for clinical study. First, the components of the pathway to build the Aspergillus cell walls were identified: because these components are not found in human cells, they are new potential targets for antifungal agents.
The genome sequence also includes the genes that produce secondary metabolites – products of the fungal machinery that have toxic, immunosuppressant or antibiotic activities. A. fumigatus has its own repertoire, not shared with other Aspergillus species.
It also contains a set of genes that lead to programmed cell death, common to many organisms. Attempts to increase the activity of these genes may provide a route for antifungal development.
Like many microorganisms, Aspergillus also has a role we regard as beneficial. It plays an essential role in the ecosystem, breaking down and recycling plant material. The fungus is a major component of compost and can grow at temperatures up to 50°C seen in compost heaps.
“Aspergillus fumigatus is like any natural component of our world. On a massive scale, it is an indispensable part of our environment – a global recycling plant. It is only when we are weakened or exposed to particularly high levels of the fungus that it becomes a lethal agent.
“It seizes the opportunity to make a home in our lungs and other tissues to wreak havoc. The detail provided by the genome sequence gives us the knowledge to develop specific diagnostics and reagents to challenge Aspergillus when we most need to.”
Dr Matt Berriman Project Manager at the Wellcome Trust Sanger Institute
Aspergillus fumigatus is one of the most ubiquitous of the airborne fungi. It has been estimated that all humans will inhale at least several hundred Aspergillus fumigatus spores each day. The vast majority of us will deal with them without harm.
However, as well as infections in sensitive patients, Aspergillus fumigatus can cause allergic reactions in some people and produces toxins.
The report details the complete 29.4 million base-pair genome sequence of Aspergillus fumigatus clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes.
More information
Participating Centres
- The Institute for Genomic Research, Rockville, Maryland 20850, and The George Washington University School of Medicine, Department of Biochemistry and Molecular Biology, 2300 Eye Street NW, Washington DC 20037, USA
- The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK
- School of Medicine and Faculty of Life Sciences, The University of Manchester, Stopford Building, Manchester M13 9PT, UK
- Departmento Microbiología II. Universidad Complutense de Madrid 28040, Spain
- Tohoku University, 1-1 Tsutsumidori-Amamiyamachi Aoba-ku, Sendai 981-8555, Japan
- School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK
- Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118, USA
- European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SD, UK
- Department of Plant Pathology, University of Kentucky, Lexington, Kentucky 40546-0312, USA
- Max Planck Institute for Terrestrial Microbiology, D-35043 Marburg, Germany
- Centro de Investigaciones Biológicas, CSIC, Madrid 28040, Spain
- Departmento Microbiologia y Genetica, Universidad de Salamanca, 37007 Salamanca, Spain
- Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de SaoPaulo, Brazil
- Department of Molecular Biology, Innsbruck Medical University, A-6020 Innsbruck, Austria
- Department of Plant Pathology, University of Wisconsin at Madison, Madison, Wisconsin 53706, USA
- Department of Biotechnology, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
- Department of Biological Mechanisms and Functions, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
- National Institute of Advanced Industrial Science and Technology, Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2-42 Aomi, Koto-ku, Tokyo 135-0064, Japan
- Unité Postulante Biologie et Pathogénicité Fongiques, INRA USC 2019, Institut Pasteur, Paris 75015, France
- Departement Structure et Dynamique des Génomes, Institut Pasteur, Paris 75724, France
- Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA
- Departments of Microbiology, Molecular Biology & Biochemistry, Center for Reproductive Biology, University of Idaho, Moscow, Idaho 83844, USA
- Department of Dermatology, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland
- Department of Bacteriology, Georg-August-University, D-37077 Gottingen, Germany
- Tokyo University of Agriculture and Technology, Saiwai-chou 3-5-8, Fuchu, Tokyo 183-0054, Japan
- Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield S10 2TN, UK
- Department of Food Microbiology and Toxicology, The University of Wisconsin, Madison, Wisconsin 53706, USA
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA
- Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan
Websites
- Publication (doi:10/1038/nature04332)
- Sanger Institute – https://www.sanger.ac.uk
- TIGR – http://www.jcvi.org
- University of Manchester – http://www.manchester.ac.uk
- Images – https://www.aspergillus.org.uk/content/genome-discovery-will-help-combat-disease-and-lead-new-drugs-language-translations-availab-0
The Institute for Genomic Research
is a not-for-profit research institute based in Rockville, Maryland. TIGR, which sequenced the first complete genome of a free-living organism in 1995, has been at the forefront of the genomic revolution since the institute was founded in 1992. TIGR conducts research involving the structural, functional, and comparative analysis of genomes and gene products in viruses, bacteria, archaea, and eukaryotes.
The University of Manchester
is the largest higher education institution in the UK, with 24 academic schools and over 36 000 students in 2005/6. Its Faculty of Medical & Human Sciences is one of the largest faculties of clinical and health sciences in Europe, with a research income of around £51 million, and the School of Medicine is the largest of its five Schools. It encompasses five teaching hospitals, and is closely linked to general hospitals and community practices across the North West of England.
Publications:
Selected websites
The Wellcome Trust Sanger Institute
The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease.
The Wellcome Trust and Its Founder
The Wellcome Trust is the most diverse biomedical research charity in the world, spending about £450 million every year both in the UK and internationally to support and promote research that will improve the health of humans and animals. The Trust was established under the will of Sir Henry Wellcome, and is funded from a private endowment, which is managed with long-term stability and growth in mind.
