Candida auris Copies Genome to Survive Antifungal Treatment, Research Reveals

New research has uncovered an unexpected mechanism by which the killer fungus Candida auris resists 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. This includes mutating a gene vital for cell wall integrity, named "Crazy-one" (CRZ1). The study is set to appear in Nature Communications and is currently available on the bioRxiv preprint server.

Study authors state these findings reveal a new adaptation mechanism for Candida auris to survive antifungal treatment, potentially leading to novel strategies against the fungus. Candida auris, first described in 2008, has unknown origins and has caused outbreaks in over 60 countries, including the U.K. It is designated a global public health threat and is on the World Health Organization's critical priority fungal pathogens list.

Dr. Hugh Gifford, clinical lecturer at the University of Exeter's MRC Centre for Medical Mycology and an intensive care physician, emphasized the fungus's danger. He noted Candida auris is rare in the general population but deadly for intensive care patients, clinging to skin and equipment, and is "incredibly hard to eradicate." If the infection enters a vulnerable patient's bloodstream, it carries a "45% death rate." Outbreaks have proven costly and disruptive, with one UK unit closing for complete refurbishment and another outbreak estimated to cost £1 million to control.

The discovery of this resistance mechanism was accidental. Researchers were testing for drug resistance when a plate of cells was left incubating longer than required. Upon return, cells had unexpectedly grown. Further tests confirmed the fungus had survived antifungal treatment by creating multiple genome copies, increasing its chance of mutating to evade drugs. Dr. Sarah Murphy, former postdoctoral researcher at City St George's University of London and co-first author, expressed surprise, stating they initially investigated why drugs weren't working despite laboratory tests showing effectiveness.

Expanding on the finding, Gifford mentioned the surprise of not identifying expected DNA mutations. Antifungal drugs target enzymes forming cell walls, causing fungi to die by shriveling, exploding, or failing to grow. He explained that surviving cells had made multiple copies of their entire genome, a "trick that other fungi have used," but not well known in C. auris. The team observed two populations: some growing slowly, others rapidly, describing this as "bet-hedging" where the bug uses "multiple tactics to increase its chances of developing resistance and evading treatment."

The rapidly growing cells exhibited a range of mutations in the CRZ1 gene, known in other organisms for its role in cell wall synthesis. Subsequent tests confirmed the rapid growth of CRZ1 mutants and that their cell walls appeared unaffected by antifungal drugs. Researchers are now exploring combined antifungal treatments through the Exeter-led UKRI-funded Fungi-CARE program, in partnership with City St George's.

Senior author Professor Tihana Bicanic, of City St George's, University of London, suggested fungal infections are "more complicated than previously thought," with "multiple populations" potentially existing during infection. She described Candida auris as having a "Swiss Army knife of innovation with their own genome," leading to "stepwise adaptation and drug resistance." Bicanic issued an "alarm for the need to make better antifungal drugs and urgently address our ability to prevent fungal deaths."

What to watch: Development of new antifungal strategies.

Editor's note: Thorough and accurate reporting on the scientific study, including technical details and expert quotes.