Deadly Fungus Candida Auris Finds New Way To Survive Antifungal Drugs, Finds Study

A deadly fungus that has emerged as a serious threat to hospital patients has been found to use an unexpected biological trick to survive antifungal treatment, raising fresh concerns about the ability to control difficult-to-treat infections.

Researchers from the University of Exeter and City St George’s, University of London, have discovered that Candida auris can survive exposure to antifungal drugs by producing multiple copies of its genome and acquiring changes in a gene involved in maintaining its cell wall.

The findings, published in Nature Communications, could help scientists understand why some fungal cells survive treatment even when laboratory tests suggest that the drugs should work.

The discovery is important because C. auris can spread in healthcare settings, persist on patients’ skin and contaminate nearby equipment and surfaces. It poses a particular risk to critically ill people, especially those in intensive care units (ICUs), whose weakened health makes them vulnerable to severe infections.

The findings also point to a challenge in treating fungal infections: resistance may not always arise through the genetic changes researchers expect. The fungus may use several strategies to survive, potentially allowing some cells to persist and adapt under drug pressure.

The research began with an effort to understand why antifungal drugs sometimes failed to eliminate C. auris, despite laboratory tests indicating that the fungus should be susceptible to treatment.

The breakthrough came unexpectedly when a researcher left laboratory plates containing fungal cells incubating for longer than planned. On returning, the team found that some cells had continued to grow despite exposure to antifungal drugs.

Further investigation revealed that surviving cells had produced multiple copies of their entire genome. This gave the fungus additional genetic material in which changes could occur, increasing the possibility that some cells would acquire characteristics helping them survive treatment.

Dr Hugh Gifford, clinical lecturer at the University of Exeter’s MRC Centre for Medical Mycology and an intensive care physician, said the team had not found the DNA mutations it initially expected.

“Somehow, these fungi had survived antifungal drugs, and we needed to find out why,” he said, describing how the researchers discovered that the surviving cells had made multiple copies of their genome.

The team also identified two groups of surviving cells. Some grew slowly, while others multiplied more rapidly. Researchers describe this use of different survival strategies as “bet-hedging”, in which a population adopts multiple approaches that may improve its chances of surviving changing conditions.

The researchers found that the more rapidly growing cells carried a range of mutations in CRZ1, a gene involved in regulating processes associated with cell wall integrity.

The fungal cell wall is an important target for certain antifungal drugs. These medicines interfere with the processes needed to build or maintain the wall, weakening the fungus and preventing it from growing or surviving.

Changes affecting cell wall regulation may help some C. auris cells withstand this pressure. The researchers' further tests supported the role of CRZ1 mutations in the rapid growth of surviving cells and found that their cell walls appeared less affected by the drugs.

Dr Sarah Murphy, former postdoctoral researcher at City St George’s and co-first author of the study, said the team was surprised to uncover an entirely new survival mechanism while investigating why treatment was not eliminating the fungus.

The findings suggest that antifungal treatment failure may involve more than the resistance mechanisms already recognised by scientists. Different groups of fungal cells may survive through different biological routes, complicating efforts to eliminate an infection.

However, the study does not mean that all C. auris infections will resist treatment or that existing antifungal medicines are ineffective. It identifies a mechanism that may help explain survival in particular circumstances and requires further investigation in patients.

First identified in 2008, Candida auris has since been reported in more than 60 countries, according to the study announcement. The World Health Organization has placed it on its critical priority list of fungal pathogens because of the public health threat it poses.

The fungus is particularly concerning in hospitals because it can persist on skin and healthcare surfaces, making infection prevention and environmental cleaning difficult. It can spread between patients, and bloodstream infections can be life-threatening, particularly among people who are already seriously ill.

Dr Gifford said that when C. auris enters the bloodstream of a vulnerable patient, the consequences can be severe. He also cited outbreaks that have caused major disruption in intensive care units, including instances in which hospital units required closure and extensive refurbishment.

Such outbreaks can place additional pressure on healthcare services, increase costs and expose already vulnerable patients to further risks.

Fungal infections have received less attention than many bacterial and viral diseases, but drug resistance among fungi is an increasing concern. The number of available antifungal medicines is also more limited than the range of drugs used against many bacterial infections.

Professor Tihana Bicanic, senior author of the study and professor of infectious diseases and mycology at City St George’s, said the findings indicate that fungal infections may be more complex than previously understood.

She described the fungus as having a “Swiss Army Knife of innovation” through changes involving its own genome, allowing stepwise adaptation and drug resistance.

Researchers are now examining possible treatment strategies, including combinations of antifungal drugs. The work is being pursued through the Exeter-led Fungi-CARE programme, supported by UK Research and Innovation, with collaboration from City St George’s.