How Candida auris Resists Antifungal Drugs

New research led by the University of Exeter has uncovered a previously unknown mechanism that allows the fungus Candida auris to resist antifungal drug treatment. The team found that the fungus creates multiple copies of its entire genome, including mutating a gene involved in cell wall integrity known as Crazy-one (CRZ1). 

According to Hugh Gifford, first author of the study published in Nature Communications, “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 percent death rate.”

The discovery came about by accident, when a researcher left plates of cells incubating longer than required for a drug resistance test and found unexpected growth. Co-first author Sarah Murphy 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.”

Gifford explained that surviving cells had made multiple copies of their entire genome, with two distinct populations emerging, some growing slowly and others more rapidly, a strategy the team calls “bet-hedging.” The faster-growing cells carried a range of mutations in CRZ1, and further tests confirmed these mutants grew rapidly with cell walls apparently unaffected by antifungal drugs.

“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,” senior author Tihana Bicanic added. “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.”