New research has revealed an unexpected new mechanism through which the killer fungus Candida auris is resisting antifungal drug treatment.
A team led by the University of Exeter and City St George's, University of London, discovered that the fungus creates multiple versions of its entire genome, including mutating a gene which plays a role in cell wall integrity, called "Crazy-one" (CRZ1).
The study is now published in Nature Communications. The research was primarily funded by the Medical Research Council, with support from the NIHR Biomedical Research Centre: Exeter.
Study authors say their findings unlock a brand new mechanism that allows Candida auris to adapt to antifungal treatment and survive, which could lead to new ways to tackle the fungus.
Candida auris was only described for the first time in 2008, and its origins remain a mystery. Since it emerged, outbreaks have been reported on every continent, in more than 60 countries in total, including the UK. It has been named a global public health threat, and is on the World Health Organization's critical priority fungal pathogens list.
Study first author Dr Hugh Gifford, Clinical lecturer at the University of Exeter's MRC Centre for Medical Mycology, is also an intensive care physician. He said: "Candida auris is rare in the general population, but it's a deadly threat to patients in intensive care units. It clings to patient skin and surrounding equipment, and can be transmitted from person to person - it's incredibly hard to eradicate. If infection enters a vulnerable patient's blood stream, there is a 45 per cent death rate.
"Outbreaks in intensive care units have been costly and highly disruptive. One unit in the UK had to close and undergo complete refurbishment to stop the outbreak, while another outbreak was estimated to cost £1 million to control."
The research team was initially testing for drug resistance when a researcher accidentally left plates of cells incubating for longer than the required test period. The researcher returned to find that cells had unexpectedly grown during this additional time period. They were surprised to find that further testing showed the deadly fungus had survived antifungal treatment by creating multiple versions of its own genome, thereby increasing its chances of mutating to evade the drug and survive.
Dr Sarah Murphy, former postdoctoral researcher at City St George's University of London and co-first author said: "We initially set out to investigate why antifungal drugs weren't working to kill Candida auris, despite laboratory tests showing that they were not resistant and that the drugs should have been effective. We were surprised to discover an entirely new mechanism for this fungus to survive - particularly with luck playing a big part of the discovery. We tested the fungus against very high concentrations of antifungal drugs. We were amazed to find there was a tiny population of cells that appeared over several days and continued to grow. Our discovery means we need to now look at new ways of treating people and eradicating this deadly fungus from hospitals."
See Dr Hugh Gifford discuss the research here.
