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Multi-resistant

Will this yeast fungus become the world's next big health problem?

In a race against time, SDU researchers are trying to understand how to combat the dreaded yeast fungus Candida auris.

By Birgitte Svennevig, , 10/31/2022

Have you heard of the yeast Candida auris? If not, then you are probably not the only one, because here in Denmark it has not attracted much attention. Yet. That may well change.

The story of Candida auris starts in 2009, when a 70-year-old Japanese woman is a patient at the Tokyo Metropolitan Geriatric Hospital. Something discharges from one of her ears, and the doctors routinely take samples of it with a cotton swab. They analyze the sample to find out what is causing the infection.

It turns out that a yeast is at play, and it's different from other known yeasts. We are all familiar with baker’s yeast, a friendly microorganism, which is used to make beer and bred. Candida auris and other Candida yeast species are very different; they cause harmful and persistent infections, which are difficult to treat with known antibiotics.

Break out in a London hospital

Against all expectations, Candida auris turns out to be unusually stress-resistant. The discovery is so unusual that the doctors decide to describe it in a scientific journal; they name it Candida auris after the place where it was found – auris means ear in Latin. Since then, the yeast has spread to all continents. Patients are almost always weakened people, and cases are almost always recorded in hospitals.

In 2015, for example, an acute infection with Candida auris has run out of control at the Royal Brompton Hospital in London.

The problem with this yeast is that it is very difficult to kill. It is multi-resistant, and thus you risk serious infections that cannot be treated.

Maria Szomek, researcher

For three months, the staff have tried everything to get rid of the infections, and finally they attempt a week-long spray attack.

All surfaces in infected rooms are sprayed with hydrogen peroxide in the hope that the spray will reach all crevices and corners.

The spray device runs for a week, and to test if any microorganisms have survived, a gel-coated plate is then placed in the middle of the room. If any micro-organisms have survived the week-long spray attack, they will be attracted to the gel and thus reveal their existence. Only one organism appears on the gel plate. Candida auris.

The first case in Denmark

In 2022, a Danish person returns home from South Africa to be admitted to a Danish hospital. The person has several wounds that need to be treated, and the South African doctors have discovered Candida auris on the patients’ skin.

The presence of a fungus on the skin is not in itself dangerous - it becomes so only when it enters the bloodstream -, but the Danish hospital takes extra safety measures to ensure that Candida auris does not spread to other patients in the hospital: The patient is admitted to two rooms, so that there is also room for the equipment needed for examinations. This ensures that the patient does not have to be moved around to other departments.

To get to the two isolated rooms, staff must go through two locks. The patient recovers and is discharged, and over a 24-hour period everything is disinfected in the rooms and in the locks.

Four cases in Denmark, so far

The next patient admitted to one of these two rooms stays there for only five hours – but that is enough for the patient to become infected with Candida auris in the bloodstream.

- It is difficult to understand how this could happen, said Maiken Cavling Arendrup, professor and head of the Unit for Mycology, Statens Serum Institut, who has followed the cases.

To date, four cases of Candida auris have been registered in Denmark, all from 2022. The three cases are on the skin of people who have returned home from abroad, while the fourth – the patient who was infected after five hours in the hospital room – was infected in the blood. Both the three carriers and the infected patient have recovered.

Need for better treatment

 - The problem with this yeast is that it is very difficult to kill. It is multi-resistant, and thus you risk serious infections that cannot be treated, said Maria Szomek from Daniel Wüstner’s research group, Department of Biochemistry and Molecular Biology, adding:

- There are many types of medicine on the market that can fight fungal infections – including Candida auris. But they are becoming less and less effective, because Candida auris is extremely good at developing resistance, so the challenge now is to develop better medicines that work. This means medicine, which not only inhibits growth of yeast but actually kills any remaining yeast cells.

Existing medicines against Candida auris and other yeasts with the potential to kill the cells are often based on so-called polyenes. Polyenes are a group of substances found naturally in certain bacteria as part of their inborn defense system. Polyenes can be extracted from the bacteria for medical use.

Can we improve nature’s own defense system?

But, as Maria Szomek points out; the mechanisms by which the polyenes kill yeast are not very well understood. This, however, is essential for developing new and improved polyene-based drugs.

- Therefore, we are working on understanding how nature's own polyenes work, Maria Szomek said.

This work takes place in Daniel Wüstner's research group at the Department of Biochemistry and Molecular Biology. In their laboratory, the group uses advanced microscopy to study what happens to a yeast cell when attacked by polyenes. The group has teamed up with colleagues in theoretical and computational chemistry, Peter Reinholdt and Jacob Kongsted and is also working with two German research teamsLeipzig University and Humboldt University Berlin.

Precision attack in the cell

The researchers do not work with real Candida auris cells, but instead with harmless models, which they expose to polyenes from the fungicide Natamycin.

- We are interested in things like: how do the polyenes get through the cell membrane? How do they bind to and interact with ergosterol, which is a subgroup of steroids and the target of the polyenes' attack, Maria Szomek explained.

The group has described their latest study of this mechanism in a scientific article.

Should we worry in Denmark?

In Denmark, all fungal infections that go into the bloodstream are examined both locally by own doctor or the hospital you are admitted to, but also by the Statens Serum Institut, which automatically receives sample of all.

- This is a fungus that we should be concerned about in many ways because it is so resistant. A Candida auris infection is not in itself a dangerous disease when we have it on the skin, but it can become one if it gets into the bloodstream, and there is a risk of that in a hospital if you are admitted to surgery or wound treatment, said Maiken Cavling Arendrup, adding:

- We see that Candida auris infections are becoming more and more frequent in all parts of the world. However, most cases or outbreaks have been reported in countries that are already known to have infection problems in hospitals and a poorer standard of hygiene than we have in Denmark.

 

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Meet the researcher

Maria Szomek is a researcher and lab manager in the group of Daniel Wüstner at the Department of Biochemistry and Molecular Biology. The group uses advanced microscopy to study what goes on in living cells, for example, when they are struck by illness. The group's work is supported by the Danish research Council, the Villum Foundation and the Lundbeck Foundation.

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Editing was completed: 31.10.2022