Candidozyma auris: Researchers find possible reason for drug failure

Petri dish with yeast Candidozyma auris: Particularly dangerous in intensive care units

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The yeast fungus Candidozyma auris, or C. auris for short, is becoming an ever-increasing health problem worldwide. For healthy people, the pathogen is usually harmless. But if it enters the bloodstream of a weakened patient, such as in an intensive care unit, the mortality rate is 45 percent.

One problem: The fungus is partly resistant to common drugs. A British research team has now found a possible explanation of how the fungus manages to escape treatment. A gene called "Crazy-one" is involved, according to the current issue of the journal "Nature Communications".

The fungus therefore produces additional copies of its entire genome when it is combated with drugs. This increases the chance that there will be gene changes in the pathogen that make it resistant to the drugs.

"Candidozyma auris is rare in the general population but poses a deadly threat to patients in intensive care units," explained lead author Hugh Gifford of the University of Exeter. The pathogen adheres to the skin of the patients and to the surrounding devices, it can be transmitted from person to person and is incredibly difficult to eliminate.

In intensive care units, the infectious fungus regularly leads to deaths. For clinics, outbreaks are also costly and associated with significant impairments, says Gifford.

The team around Gifford had investigated why two seriously ill patients infected with the fungus could not be cured, despite receiving a drug that attacks the cell wall of the fungus. Although it was known that certain gene changes can make the fungus resistant to the drug, they were not present in both cases.

Intensive care unit (symbolic image): C. auris is difficult to eliminate

During the investigation, the researchers came to the aid of chance: One scientist had accidentally cultivated plates containing C. auris and a drug against fungi for longer than intended. Only then did they notice that a tiny part of the cells had continued to grow over several days, the researchers report.

Over time, two variants of the mushroom grew, one small and one large. The little one grew slower, the big one faster. Further tests showed that the fungus had formed additional copies of its entire genome. This increased the chance for mutations that make it resistant.

In fact, in the fast-growing, large variant, the scientists were able to detect more such changes in the gene CRZ1, also called "Crazy-one" because of the letter sequence, than in the other samples. CRZ1 is associated with the stability and rebuilding of the cell wall. The researchers suspect that the gene changes have caused the drug to have little effect on the cell wall of the fungus.

"Our discovery means that we now need to look for new ways to treat patients and eliminate this deadly fungus from hospitals," the researchers conclude. They now want to consider different options such as a combined use of different drugs.

C. auris, formerly known as Candida auris, was first described in Japan in 2009, its origin is still a mystery. Since its occurrence, outbreaks have been reported on all continents, in total in more than 60 countries. It has been classified as a global threat to public health and is on the list of fungal pathogens with the highest priority of the World Health Organization (WHO).

According to data from the EU health authority ECDC, Germany is one of the EU countries with the most reported cases. Currently, there are relatively stable about 100 first proofs of C. auris per year, said Oliver Kurzai, board member of the Institute of Hygiene and Microbiology at the University of Würzburg, who was not involved in the British study. There are always outbreak events, and with the spread of the pathogen, especially in southern Europe, the probability of increased imports increases.

“We therefore have to fear that the number of cases will increase in the next few years,” said Kurzai, who heads the National Reference Center for Invasive Fungal Infections (NRZMyk). In Germany, there is now a reporting obligation for proof.

Why exactly the number of fungal infections is increasing is unclear. Improved diagnostic options are considered as a factor, whereby the fungi are discovered in the first place.

Experts also believe it plausible to have a possible connection with climate change, mainly with warming and long droughts and droughts. “These lead to fungi potentially spreading better, as the spores are transported with dust and soil over the air,” writes the British research team. This has not yet been proven.