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.”
Expanding further on the finding, Dr Hugh Gifford said: “This study had a number of surprising elements. Firstly, we did not identify any of the DNA mutations that we might have expected. Antifungal drugs target the enzymes that make cell walls, so that fungi die by shriveling, exploding, or not being able to grow. Somehow, these fungi had survived antifungal drugs, and we needed to find out why. We were surprised to find that surviving cells had made multiple copies of its entire genome. This is a trick that other fungi have used in the past, but not one that is well known in C. auris . In fact, there were two populations, some growing slowly, others growing more rapidly. We call it ‘bet-hedging’ when a bug uses multiple tactics to increases its chances of developing resistance and evading treatment.”
The team found that the more rapidly growing cells contained a wide range of mutations in a gene that has been studied in other organisms for its role in governing cell wall synthesis, called “Crazy-one” ( CRZ1 ). Further tests confirmed the rapid growth of CRZ1 mutants, and that their cell walls appeared to be unaffected by antifungal drugs.
Researchers are now looking at options including the use of antifungal drugs in combination, which is being addressed via the Exeter-led UKRI funded Fungi-CARE programme , also in partnership with colleagues at City St George’s.
Senior author Professor Tihana Bicanic, Professor of Infectious Diseases and Mycology at the School of Health & Medical Sciences at City St George’s, University of London, said: “We now believe that fungal infections are more complicated than previously thought. Multiple populations may exist during infection. New and emerging human fungal infections, like Candida auris , essentially have a Swiss Army Knife of innovation with their own genome, leading to stepwise adaptation and drug resistance. The implication of these results are that we now know a new mechanism of evolution that weakens our antifungal drug arsenal. So, we are sounding the alarm for the need to make better antifungal drugs and urgently address our ability to prevent fungal deaths.”
The study is titled ‘ FKS1 /2-variant independent mechanisms underlying the 1 emergence of resistance in echinocandin-refractory 2 Candida auris infections ’ and is published in Nature Communications .
Nature Communications
Experimental study
Cells
FKS1/2-variant independent mechanisms underlying the emergence of resistance in echinocandin-refractory Candida auris infections
15-Oct-2026