Unusual Fungus Has the Potential To Become a Global Health Problem

A New Yeast Fungus

Have you ever heard of the yeast Candida auris? If not, you are most likely not the only one since it hasn’t garnered much attention. Yet. That could change.

Candida auris’s story begins in 2009 when a Japanese woman in her 70s is admitted to the Tokyo Metropolitan Geriatric Hospital. Her ear sometimes discharges something, and the doctors routinely use a cotton swab to collect samples of it. To determine what is causing the infection, they analyze the sample.

It turns out that a yeast, different from other known yeasts, is at play. We’ve all heard of baker’s yeast, a friendly microorganism used to make beer and bread. Candida auris and other Candida yeast species are extremely different; they cause serious and persistent infections that are difficult to treat with known antibiotics.

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Break out in a London hospital

Against all expectations, Candida auris turned out to be unusually stress-resistant. The finding is so unusual that the doctors decide to document it in a scientific journal; they name it Candida auris after the location where it was discovered – auris meaning ear in Latin. Since then, the yeast has spread to every continent. Patients are almost always weakened individuals, and incidents are virtually always recorded in hospitals.

For instance, the Royal Brompton Hospital in London had an out-of-control acute Candida auris infection in 2015. The team had tried everything to get rid of the infections for three months, and eventually, they launched a week-long spray attack. They sprayed all surfaces in infected rooms with hydrogen peroxide in hope that the spray will reach all crevices and corners. 

The spray device ran for a week, and to test if any microorganisms have survived, a gel-coated plate was placed in the middle of the room. Any microorganisms that managed to withstand the week-long spray onslaught will be drawn to the gel and therefore reveal their existence. Only one organism appears on the gel plate. Candida auris.

The first case in Denmark

In 2022, a Danish person returned home from South Africa to be admitted to a Danish hospital. The person had several wounds that need to be treated, and the South African doctors had discovered Candida auris on the patient’s 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 took extra safety measures to ensure that Candida auris did not spread to other patients in the hospital: The patient was admitted to two rooms so that there is also room for the equipment needed for examinations. This ensured that the patient did not have to be moved around to other departments.

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

Four cases in Denmark, so far

The next patient admitted to one of these two rooms stayed there for only five hours – but that was 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 in Denmark, who has followed the cases.

To date, four cases of Candida auris have been registered in Denmark, all from 2022. 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 the 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 teams at Leipzig 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.

Reference: “Natamycin sequesters ergosterol and interferes with substrate transport by the lysine transporter Lyp1 from yeast” by Maria Szomek, Peter Reinholdt, Hanna-Loisa Walther, Holger A. Scheidt, Peter Müller, Sebastian Obermaier, Bert Poolman, Jacob Kongsted and Daniel Wüstner, 29 July 2022, Biochimica et Biophysica Acta (BBA) – Biomembranes.
DOI: 10.1016/j.bbamem.2022.184012

The study was funded by the Villum Foundation, the Lundbeck Foundation, and the Independent Research Fund Denmark.