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.