A superhero fungus for better drugs

 

(Posted: 22 June 2015)

In the wild, Cunninghamella elegans is a pretty humdrum fungus. It hangs out in the soil, particularly near coastal areas, and it is generally harmless to humans. But Cunninghamella is a superhero when it comes to testing and developing drugs in the lab, and Dr Cormac Murphy is harnessing its power.

“Enzymes called cytochromes P450 are involved in drug metabolism in humans and in other mammals in our liver, and Cunninghamella has cytochromes P450 as well,” he explains. “And numerous studies have shown that for different drugs Cunninghamella does metabolise drugs in the same way as mammals.”

When drugs are broken down - whether in the liver or in the fungus - it results in chemicals called drug metabolites, and regulatory bodies in medicine want evidence that such metabolites don’t themselves pose a safety issue.

This is where Dr Murphy, a Senior Lecturer, UCD School of Biomolecular and Biomedical Science, sees Cunninghamella offering a useful service. “It’s relatively easy to grow these micro-organisms in the lab in large numbers, and you can add your drug to the fungal cells growing in the flask, then the fungus will produce the metabolites that you want to test,” he says. “We think this has the potential to be more efficient than producing the metabolites through organic chemical synthesis or dosing laboratory animals - the fungus does the work for you.”

Dr Murphy and his lab have also discovered that when the fungus forms a ‘biofilm’ or flat aggregation of cells that stick together, they can produce metabolites even more efficiently. “Biofilms are hard to kill and can be bad news when they form on medical equipment, but in this case the stability of the biofilm is a good thing,” he says. “It means that instead of growing the fungus in a huge big vat, we can grow it in a smaller volume and the fungus is active over a much longer period of time.”

The fungus can also help scientists to fine-tune drug compounds, adds Dr Murphy, who together with colleagues at the University of Durham has developed a Cunninghamella-based system to work out where putting a fluorine atom on a drug could slow down its metabolism.

“We have found that by putting a non-fluorinated drug into Cunninghamella, and tracking how it is broken down, we can predict the best sites for fluorine,” he explains. “Then our collaborators in Durham make the fluorinated drug and we test it out on the fungus. Using this method we have been able to completely stop metabolism of the potential drug, which is quite neat.”

Aside from drug testing and development, Cunninghamella also seems to have a talent for taking dyes out of water, which could be of interest to the global textile industry, adds Dr Murphy. “We can remove the dye malachite green from water just using the fungal biofilm,” he says. “You can see the liquid going clear and the fungus goes green at first, then the colour disappears from the biofilm, and we could use the same biofilm for a month, it just kept on working. So the fungus has a number of uses, we are trying to squeeze the most out of it.”

Dr Cormac Murphy, Senior Lecturer from UCD School of Biomolecular and Biomedical Science, was interviewed by freelance journalist Dr Claire O'Connell.