Researchers in the U.K. have uncovered a new way Candida auris resists antifungal drugs. Their study, published in Nature Communications, reveals the fungus creates 2–4 copies of its entire genome, including mutations in key genes, to boost its survival odds.
“We now believe that fungal infections are more complicated than previously thought,” said Tihana Bicanic, MD, professor of infectious diseases and mycology at the School of Health & Medical Sciences at City St George’s, University of London. “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.”
C. auris infections are a growing threat to public health, listed as a critical priority fungal pathogen by the World Health Organization (WHO). Since the fungus was first described, nearly 20 years ago, outbreaks have been reported in over 60 countries, with highly disruptive and costly consequences for intensive care units across the world.
“Candida auris is rare in the general population, but it’s a deadly threat to patients in intensive care units,” said Hugh Gifford, MD, PhD, intensive care physician and clinical lecturer at the University of Exeter’s MRC Centre for Medical Mycology. “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% death rate.”
Gifford’s team discovered this mechanism by accident. During drug resistance tests, a researcher left cells incubating longer than intended. Instead of dying, the fungus thrived. Further testing showed the surviving cells had created multiple genome copies, increasing their mutation rate to evade treatment.
“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,” said Sarah Murphy, PhD, former postdoctoral researcher at City St George’s, University of London and co-first author of the study. “We tested the fungus against very high concentrations of antifungal drugs [and] were surprised to discover an entirely new mechanism for this fungus to survive, particularly with luck playing a big part of the discovery.”
Some surviving cells grew faster, carrying mutations in the CRZ1 gene, which plays a role in cell wall synthesis. These mutations made the cell walls resistant to antifungal drugs, which typically target cell wall enzymes.
This mechanism, while known in other fungi, was not previously associated with C. auris. The discovery opens new treatment avenues, with researchers now exploring antifungal drug combinations through the Fungi-CARE programme, funded by the U.K.’s Medical Research Council.
