Asexual revolution breaks out in the lab

UCD researchers have discovered a deadly fungus that may help transplant and other patients who are at high risk from a common fungus

THE SECRET SEX LIFE of a killer fungus has been discovered for the first time - and it happened in an Irish lab. The discovery has taken nearly a century and a half to find and could now pave the way for more effective measures against Aspergillus fumigatus, which poses a major medical threat to people on chemotherapy or following a transplant.

The mould grows on decaying organic matter - such as compost heaps, damp hay and debris in ventilation systems - and releases its spores into the air to disperse in nature. Each day we inhale around 100 of those spores, and for healthy people it's not a problem.

But for people with weakened immune systems the spores can cause a potentially lethal infection called aspergillosis, which is the leading infectious cause of death in leukaemia and bone-marrow transplant patients. In addition, the spores can trigger asthma and allergies in susceptible people.

First described 145 years ago, the fungus was thought to reproduce only asexually, but recent advances in genetics signalled something else was afoot, according to mycologist Hubert Fuller from University College Dublin's school of biology and environmental science.

"Because it's such an important human pathogenic fungus it was selected a few years ago to have its genome sequenced, and genes were identified that were known to have some involvement in mating," he says.

"It contains all of the genetic machinery needed to engage in sex, and populations of the fungus were also shown to consist of two different 'mating types' or sexes - the fungal equivalent of males and females. This was strong evidence that the fungus might have a covert sexual cycle."

Fuller and Ircset-funded PhD student Céline O'Gorman collected airborne spores of A fumigatusfrom five sites around Dublin over the course of a year and set up mating crosses in the lab, growing them on plates of oatmeal-based food.

"We put them away in an incubator, but we weren't too hopeful about them, because no one had ever seen a sexual stage in this fungus," says Fuller.

Around six months later, O'Gorman took out the cultures and saw some tiny whitish-yellow structures, which she examined under the microscope and found to be fruiting bodies, indicating the cultures had reproduced sexually.

"I still remember the moment," she says. "One day I said it's about time to go back to them, so I started to look at a couple of the cultures. When I saw the fruiting bodies I knew what they were straight away, and of around 80 cultures, practically every strain had them."

O'Gorman travelled to the University of Nottingham where she and collaborator Dr Paul Dyer used DNA analysis to confirm that the parent moulds were A fumigatus and not lookalikes, and that the offspring had inherited traits of both parents. The results showed that a full sexual exchange had taken place.

The world-first observation, published online in the important journal Nature this week, means that scientists can now carry out experiments on the fungus to better understand its genetics and hopefully develop new strategies to control it, says Fuller.

"The discovery is significant for both good and bad reasons. On the downside, the fact that Aspergillus fumigatus can reproduce sexually, generating genetic variation, means that it is more likely to become resistant to anti-fungal drugs over shorter time periods, and the sexual spores are better at surviving harsh environmental conditions," he says.

"But on the positive side, the newly discovered sexual cycle can be used as a valuable tool in lab experiments to try to work out how the fungus causes disease, and once the genetic basis of disease is understood, then researchers can look to devising methods to control and overcome the fungus. It may also help identify better markers for infection in the early stage."

Fuller notes that some other medically important fungi, like the organism that produces penicillin, have no known sexual stage, but it could be a case of needing to look a little further. "Some of these species have apparently functional sex-related genes, and [our] discovery could lead to a sexual revolution for many other of these supposed 'asexuals'."