A special mechanism helps the deadly hospital fungus Candidozyma auris evade treatment. A gene called “Crazy-one” is involved, reports a research team in the journal “Nature Communications”.
The fungus produces additional copies of its entire genome under drug pressure, thereby increasing the likelihood that certain changes - such as those in the "Crazy-one" (CRZ1) gene - will lead to resistance. “Candidozyma auris is rare in the general population but poses a fatal threat to patients in intensive care units,” said lead author Hugh Gifford from the University of Exeter.
The pathogen adheres to the patient's skin and surrounding devices, it can be transmitted from person to person and is incredibly difficult to eliminate.
“If the infection enters the bloodstream of a weakened patient, the mortality rate is 45 percent.” Outbreaks in intensive care units are also costly for hospitals and cause significant disruption.
Gifford's team investigated why two seriously ill patients could not be cured despite treatment with an echinocandin. Echinocandins are a class of drugs that attack the cell wall of the fungus and are considered the drug of first choice against such Candidozyma infections. So far, resistance to these drugs has been primarily associated with changes in the FKS1 and FKS2 genes - but the researchers did not find such changes in the cases examined.
In the course of the analyses, chance came to the rescue: a researcher accidentally cultured plates containing Candidozyma auris and the antimycotic anidulafungin for longer than intended, it was said. Only then did it become apparent that a tiny portion of the cells had continued to grow over several days. Longer culture also resulted in two significantly different colony forms: small and large variants. The small ones grew slower, the larger ones grew faster.
Tests showed the deadly fungus had survived treatment with antifungal drugs by making extra copies of its entire genome, increasing its chances of mutating and escaping the drug.
The faster-growing cells of the larger fungal colonies carried significantly more mutations in the CRZ1 gene than the original isolates and the small variants. CRZ1 is associated with cell wall stability and remodeling. Further tests suggested that the cell wall response of the rapidly growing cells to antifungal drugs was altered.
The researchers see the results as an indication that resistance cannot develop suddenly, but rather gradually: first more tolerance, then further genetic changes and finally more pronounced resistance.
“Our discovery means we must now look for new ways to treat patients and eliminate this deadly fungus from hospitals,” the researchers conclude. They want to examine options such as a combined use of different antifungal medications.
Candidozyma auris – previously called Candida auris – was first described in Japan in 2009, but its origin remains a mystery. Since its emergence, outbreaks have been reported on every continent, totaling more than 60 countries. It has been classified as a global public health threat and is on the World Health Organization (WHO) list of top priority fungal pathogens.
According to data from the EU health authority ECDC, Germany is one of the EU countries with the most reported cases. At the moment there are relatively stable around 100 initial detections of Candidozyma auris per year, said Oliver Kurzai, head of the Institute for Hygiene and Microbiology at the University of Würzburg, who was not involved in the British study. There are always outbreaks and as the pathogen spreads, especially in southern Europe, the likelihood of increased imports increases.
“We therefore have to fear that the number of cases will increase in the next few years,” explained Kurzai, who heads the National Reference Center for Invasive Fungal Infections (NRZMyk). In Germany there is now an obligation to report evidence. Echinocandin resistance is currently rare in this country. They were found in less than five percent of the detected C. auris strains.
In the USA, the development of another dangerous fungus is already causing concern: Cladophialophora bantiana. Infections with it are fatal in 60 to 70 percent of cases, according to the US health authority CDC. The number of detections in a clinical reference laboratory increased - at a low level - by around four times from 2023 to 2025. “The reasons for the apparent increase are unknown.”
As a rule, the molds cause brain abscesses, according to the Robert Koch Institute (RKI). Infections caused by C. bantiana occur worldwide. People in their fifth decade and older are mostly affected. In Germany, infections with the fungus are still a rarity, said Kurzai. There is currently no systematic recording.
The possible causes for increases in the number of fungal infections are diverse, one factor being improved diagnostic options. A connection with climate change is plausible, especially with warming and long periods of drought and dryness. “These lead to mold potentially spreading more easily because the spores are transported through the air with dust and soil.” So far this is only a hypothesis; there is no direct proof.
