Researchers in Ireland and the UK have found that a lethal fungus, Aspergillus fumigatus, reproduces sexually. The findings represent a major breakthrough in the understanding of this pathogen, which causes death in 50% of infected immune-deficient patients. The study was funded in part by a Marie Curie grant from the EU and is published in the journal Nature.

A. fumigatus spores are widespread in the atmosphere. Although everyone inhales some of these spores on a regular basis, a healthy immune system will normally eliminate them. However, a weakened immune system is easily overcome by this opportunistic airborne fungus; A. fumigatus is the leading cause of death by infection in leukaemia and bone-marrow-transplant patients.

The spores are also associated with severe asthma and allergic sinusitis in humans, and with stonebrood (mummification) in honey-bee colonies.

The fungus, which plays an important role in nutrient recycling in soils, was first described 145 years ago and has been the subject of ongoing study ever since. Until this latest discovery, it was only observed to reproduce asexually. Sexual reproduction enables organisms to diversify and adapt, making it a highly desirable trait in beneficial fungi. Finding sex-related genes in pathogenic fungi has very important implications for controlling fungal infection.

Dr Paul Dyer of the University of Nottingham in the UK is an expert in the sexual development and population variation of fungi. The discovery provides both good and bad news, he said. "The bad news is that we now know that Aspergillus fumigatus can reproduce sexually, meaning that it is more likely to become resistant to antifungal drugs in a shorter period, and the sexual spores are better at surviving harsh environmental conditions. The good news is that we can use the newly discovered sexual cycle as a valuable tool in laboratory experiments to try to work out how the fungus causes disease and triggers asthmatic reactions."

Dr Dyer and PhD student Céline O'Gorman of the University College Dublin in Ireland performed a thorough genetic analysis of an Irish environmental population of A. fumigatus composed of 91 different isolates collected from 5 locations in Dublin during 2005. They observed the fungus's sexual reproductive structures using light microscopy and scanning electron microscopy, and sorted the samples into all possible combinations of 'mating types'. The paired-off fungi were incubated in the dark.

The researchers noted that reproduction was heterothallic; that is, sexual reproduction happened when isolates were of complementary mating types. Previous efforts to induce sexual reproduction in A. fumigatus may have failed because the environmental conditions required to trigger sex may be highly specific, according to the study.

In nature, the process most likely takes place in compost heaps but no one has studied the fungus in compost-heap conditions, Ms O'Gorman explained to CORDIS News. In this study, the scientists grew the fungus in hot temperatures and used a homemade agar base (made with oatmeal). In addition, the samples were grown for a full six months; much longer than in previous studies. These factors combined may have served to imitate compost-heap conditions, she speculated.

The genetic analysis of A. fumigatus also provided valuable insights. 'Once we understand the genetic basis of disease we can then look forward to devising methods to control and overcome the fungus,' said Dr Dyer.

"The discovery of a sexual cycle in A. fumigatus provides insights into the biology and evolution of the species," the study concludes. It helps explain why there are so many varieties of the fungus (which one wouldn't see if they were reproducing clonally), and why it has sex-related genes. It can also explain aspects of the evolution of the A. fumigatus genome, and the ability of the spores to survive even in adverse environmental conditions.

The findings shed new light on the biology of this medically important fungal species, and on its resistance to antifungal drugs. Results of this research will hopefully lead to improved treatment and new ways of controlling A. fumigatus infection.

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