Candida auris is hard to diagnose and is resistant to many antifungal drugs.

Study sheds light on killer fungus

Scientists have identified an "Achilles heel" that could help in the fight against a killer fungus.

Candida auris, which first surfaced in 2009 and kills 30-60% of people who become infected, is hard to diagnose and is resistant to many antifungal drugs.

A research team, led by Radboud university and including staff from the University of Exeter, has discovered that the human immune system actually recognises the fungus well.

Specific unusual components of the cell wall of the fungus play an essential role in this recognition – and this provides a possible route to effective drug treatments.

"Our research not only shows that these cell wall components are important for the detection by the immune system, but also that they are indispensable to the fungus," said Professor Alistair Brown, deputy director of the MRC Centre for Medical Mycology at the University of Exeter.

"Drugs that selectively block the production and operation of these components are currently being investigated for safety and effectiveness.

"Perhaps one of these is the ideal candidate to tackle the fungus."

Since these cell wall components are indispensable to C. auris, the risk of resistance to such a new drug is small.

In order to develop resistance, the fungus must at least remain alive so that it can gradually adapt to the new drug.

Hospital control

Last year, the New York Times published an alarming article about the growing problem of C. auris.

The authors cited the example of a man infected with C. auris who died after 90 days at Mount Sinai Hospital.

The fungus, which in the meantime had settled in the mattress, curtains, walls, telephone, basically everywhere in the hospital room, could only be disinfected with a lot of effort.

Only after special cleaning and removal of part of the ceiling and the tile floor did the hospital control the fungus.

Reduced immunity

"We started to investigate C. auris with international colleagues because there was virtually nothing known about this fungus," said Mariolina Bruno of Radboud university medical center’s Department of Internal Medicine.

The research results have now been published in Nature Microbiology.

The study shows that the fungus is especially dangerous for people with compromised immunity.

"A well-functioning immune system recognises the fungus clearly and can control it well," Bruno said.

Diagnosis and monitoring

C. auris is related to the much better-known Candida albicans, which can cause vaginal fungal infections as well as potentially fatal infections when it invades the whole body.

In the study, C. albicanshas therefore served as a comparator fungus.

Bruno said: "On the one hand, we see that C. auris evokes a better immunity reaction than C. albicans.

"On the other hand, C. auris appears less pathogenic, but once in the bloodstream, both fungi are usually life-threatening."

What makes the problem even worse is that C. auris is not so easy to identify.

This makes it easy to confuse with other fungi, which can lead to a delay in treatment.

Jacques Meis, a physician-microbiologist at the Canisius-Wilhelmina Hospital, said: "You should determine the fungi type on a molecular level, enabling you to immediately see which fungus you are dealing with, but not every laboratory has the facilities for that."

Earlier this year, he and Paul Verweij (Radboud University medical center) called for the nation-wide monitoring of serious fungal infections to gain a better understanding of the burden of disease and mortality rates.

Global warming?

The question why C. auris suddenly appeared in 2009 has still not been answered.

The fungus was not found in stored patient material from previous years, so it seems to be a new fungus that has quickly spread across the world.

Perhaps global warming plays a role, suggests American microbiologist Arturo Casadevall in TIME.

Most fungi thrive at relatively low temperatures, but due to an increase in the average temperature, it is conceivable that a fungus breaks through its thermal restriction and can suddenly colonise the human body.

Bruno called this an "interesting point of view", but added: "Without further evidence, it is as yet highly speculative.

"Apart from the actual origin history or 'birth' of C. auris, the article in Nature Microbiology provides information on how the interaction between humans and the fungus C. auris occurs: how the fungus stimulates the immune system, what C. auris' pharmacological Achilles heel is and what the opportunities for immunotherapy are."

Date: 2 September 2020

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