Ubiquitous, Essential ... but Deadly

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Press Releases: 21st December 2005

Aspergillus fumigatus on Czapek dox agar showing typical blue-green surface

pigmentation with a suede-like surface consisting of a dense felt of

conidiophores. Credit: _Dr Ellis_

(http://www.mycology.adelaide.edu.au/gallery/photos/aspergillus09.html) , School

of Molecular & Biomedical Science,

University of Adelaide.

Ubiquitous, Essential ... but Deadly

Genome sequence of fungus reveals its weapons

The genome sequence of the most common mould that causes disease worldwide is

published in _Nature_

(http://www.nature.com/nature/journal/v438/n7071/abs/nature04332.html) 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.

Dr Arnab Pain, lead author at the Wellcome Trust Sanger Institute, said, " 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. "

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% 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.

We have discovered a treasure trove of new and important genes in

Aspergillus

Dr Arnab Pain

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. Microscopic view of Aspergillus

fumigatus showing conidial (spore-bearing) heads. Credit: _Dr Ellis_

(http://www.mycology.adelaide.edu.au/gallery/photos/aspergillus10.html) , School

of

Molecular & Biomedical Science, University of Adelaide.

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, " said Dr

Matt Berriman, Project Manager at the Wellcome Trust Sanger Institute. " 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 is 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. "

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.