Researchers from City St George’s, working with colleagues at the University of Exeter, have discovered an unexpected new mechanism that allows the deadly fungal pathogen Candida auris to survive antifungal treatment, opening up new avenues for tackling one of the world’s most concerning emerging infections.
By Lisa Jones (Press and Research Communications Manager), Published
Published today in Nature Communications, the study found that Candida auris can create multiple versions of its entire genome and develop mutations that help it withstand treatment, revealing a previously unrecognised route to antifungal drug resistance.
First identified in 2008, Candida auris has since caused outbreaks in more than 60 countries including the UK and is listed by the World Health Organization as a critical priority fungal pathogen. The fungus can spread rapidly within healthcare settings and cause life-threatening infections in vulnerable patients.
“Swiss Army Knife of innovation”
Professor Tihana Bicanic, Professor of Infectious Diseases and Mycology at City St George’s School of Health & Medical Sciences, 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 team originally set out to investigate why antifungal drugs appeared ineffective against some Candida auris cells despite laboratory tests suggesting the fungus should be susceptible to treatment. A chance observation during the experiments revealed that a group of cells had continued to grow after prolonged exposure to antifungal drugs.
The surviving fungal cells created multiple copies of their genome, increasing the chances of developing genetic changes that could help them withstand treatment.
They found that the more rapidly growing cells contained a wide range of mutations in a gene called “Crazy-one" (CRZ1), which plays a vital role in fungal cell wall integrity. These mutations appeared to enable some cells to continue growing despite exposure to antifungal drugs.
Dr Sarah Murphy, a former postdoctoral researcher at City St George’s and co-first author of the study, said:
“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."
Dr Hugh Gifford, co-first author of the study at the University of Exeter’s MRC Centre for Medical Mycology, added:
"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."
The study was funded by the Medical Research Council, with support from the NIHR Biomedical Research Centre Exeter. Researchers are now exploring new treatment approaches, including combinations of antifungal drugs.