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Scientists investigate disease-causing properties of 'peacock of the fungal world'

3 June 2008

Penicillium
Members of the Penicillium family of fungi are almost exclusively ‘good’, with uses including antibiotic development and cheese ripening. But one member of the family is responsible for the third commonest serious illness in patients with HIV in South-east Asia.

Now, scientists at Imperial College London have received almost £350 000 from the Wellcome Trust, the UK's largest medical research charity, to study Penicillium marneffei, the only Penicillium fungus to cause serious disease in humans. The researchers aim to find out what makes this particular fungus pathogenic.

The Penicillium family of fungi has 261 known members. Arguably the most well known is Penicillium chrysogenum, commonly found in nature: the discovery of its bacteria-killing properties by Sir Alexander Fleming led to the development of penicillin and heralded the antibiotic revolution. Other members include moulds commonly used in the production of blue and soft cheeses, such as Penicillium camemberti and Penicillium glaucum, used for camembert and gorgonzola respectively.

Penicillium marneffei, however, is a human pathogen, causing penicilliosis in humans. Once considered rare, penicilliosis has become far more common as an opportunistic infection in people with HIV. It is estimated that between one in ten and one in five infections in people living with HIV in South-east Asia is caused by the fungus. Symptoms include skin lesions, fever, cough and respiratory disease, but the disease is often misdiagnosed.

"Penicillium marneffei is the peacock of the fungal world, a striking scarlet and golden colour in culture, but its colour belies the fact that it can cause serious illness in patients with HIV," says Dr Matthew Fisher from Imperial College London, who will lead the new study.

"The fungus exists exclusively in South-east Asia, infecting small mammals like the bamboo rat without making them ill. We still don't really understand where the fungus exists in nature but think that it lives in the soil, infecting both rats and humans independently. It's likely that many more people encounter the fungus than contract penicilliosis, but only those with compromised immune systems become ill."

Dr Fisher and colleagues will capitalise on the information obtained from the Penicillium marneffei genome and that of its nearest relative, the non-pathogenic Talaromyces stipitatus, both of which were sequenced by the J Craig Venter Institute in the US. The researchers hope that a comparison of these two genomes will enable them to identify additional - or missing - genes that lead the Penicillium fungus to be pathogenic. In addition, they will also study how the fungus has evolved, looking at rapid changes in its genetic make up that have enabled it to become pathogenic.

Most fungi exist as hyphae (multicellular, branching structures) while others exist as yeast (unicellular forms). Pathogenic fungi tend to be yeasts. However, a small number of fungi - including Penicillium marneffei - are "dimorphic", able to switch from one form to another, usually becoming a yeast at 37°C. Dr Fisher believes that the pathogenicity of Penicillium marneffei is likely to lie in the genes that facilitate this switch.

The researchers hope that understanding which genes enable the fungus to survive in the environment and to be pathogenic may enable the development of new treatments in the future.

Drugs toxic to fungi tend also to be toxic to vertebrates, says Dr Elaine Bignell also at Imperial College, who will be working with Dr Fisher.

"Penicilliosis can be treated with antifungal drugs, but these manage rather than clear the infection," says Dr Bignell. "By understanding which genes make it pathogenic, we may be able to identify new targets which help us develop novel treatments without the same toxicity."

The Imperial College team will work in collaboration with researchers at the University of California at Berkeley and the J Craig Venter Institute in the US, and the University of Melbourne, Australia.

Contact

Craig Brierley
Media Officer
Wellcome Trust
T
020 7611 7329
E
c.brierley@wellcome.ac.uk

Notes for editors

1. The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £650 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.

2. Rated as the world's fifth best university in the 2007 Times Higher Education Supplement University Rankings, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts over 12 000 students and 6000 staff of the highest international quality.

Innovative research at the College explores the interface between science, medicine, engineering and management and delivers practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

With 66 Fellows of the Royal Society among its current academic staff and distinguished past members of the College including 14 Nobel Laureates and two Fields Medallists, Imperial's contribution to society has been immense. Inventions and innovations include the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of its research for the benefit of all continues today with current focuses including interdisciplinary collaborations to tackle climate change and mathematical modelling to predict and control the spread of infectious diseases.

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