Genome discovery may lead to new drugs

A group of researchers think they have cracked the gene code behind a key family of fungi, which includes the leading cause of death in leukaemia and bone marrow transplant patients. The genome discovery could help combat disease and lead to new drugs.

The importance of the project will go some way in helping to develop new drugs and diagnostic tests, as well as understand and prevent allergies and diseases like pneumonia and sinusitis.

In addition, the information revealed could also develop understanding of the biology of composting and mycotoxin production, providing benefits for many other areas of science and medicine.

The scientists, from the University of Manchester, have been experimenting with fungi, specifically Aspergillus fumigatus, Aspergillus nidulans and Aspergillus oryzae.

Experiments performed revealed that these three species displayed only around 68 per cent of the same proteins, a similar percentage to that shared by mammals and fish, which diverged 450 million years ago.

They also differ considerably in genome size, with Aspergillus oryzae being 31 per cent bigger than Aspergillus fumigatus and 24 per cent bigger than Aspergillus nidulans. Intriguingly, over 30 per cent of the 9,500-14,000 genes identified are new to science and of unknown function and structure.

"Aspergillus fumigatus is a major constituent of compost, and mould fungi have been important sources of drugs including penicillin and ciclosporin (for transplantation)," said David Denning, co-ordinator of the project.

"However, the species also produces toxins known as mycotoxins, such as aflatoxin which can cause liver cancer. Aspergillus causes a life-threatening infection for transplant and leukaemic patients, as well as being a major allergen for asthmatics," he added.

These results have been reported in three different papers in the 22 December issue of Nature magazine.

Aspergillus is a very common air-borne fungus, carried all over the world as spores. Although usually harmless, the species Aspergillus fumigatus was identified as a cause of infection as long ago as 1848 and is now the leading infectious cause of death in vulnerable leukaemia and bone marrow transplant patients.

Aspergillus fumigatus is unique in causing infection at both extremes of the body's immune function. Aspergillosis (the diseases caused by Aspergillus) mainly invades the lungs and sinuses, but can spread to other organs such as the brain.

As well as leukaemia and bone marrow transplant patients, 'invasive aspergillosis' is increasingly affecting other hospital patient groups and is very difficult to treat. Up to half of sufferers die of the condition, and as many as 1 in 25 patients who die in modern European teaching hospitals are now suffering from it.

Other immuno-compromised patients (transplantation, AIDS, steroid treatment etc) are increasingly being affected with life-threatening Aspergillus pneumonia and sinusitis.

Aspergillus can worsen asthma and cause allergic sinusitis in patients with allergic tendencies, and can also get into lung cavities created by tuberculosis (which affects a third of the world's population) causing general ill-health and bleeding in the lung. The fungus also causes plant and animal diseases.