FROM THE SAME FAMILY OF YEAST THAT GIVE US BEER AND SOURDOUGH BREAD IS THE LURKING DANGER OF SERIOUS FUNGAL INFECTIONS THAT HAVE THE ABILITY TO KILL

NEW FUNGAL THREAT WHICH KILLS 1.7 MILLION PEOPLE A YEAR SPREAD BY BIRDS AND CLIMATE CHANGE IS ON THE MARCH SAY SCIENTISTS FROM THE UNVERSITY OF THE FREE STATE IN SOUTH AFRICA

FROM THE SAME FAMILY OF YEAST THAT GIVE US BEER AND SOURDOUGH BREAD

IS THE LURKING DANGER OF SERIOUS FUNGAL INFECTIONS THAT HAVE THE ABILITY TO KILL 

SEO: fungal infection, Prof Carlien Pohl-Albertyn, bacteria, Fungi, yeast, microbiome, Penicillium, unicellular fungi, Candida albicans

A serious fungal infection has the ability to kill you. Yet few people, especially those with a weakened immune system, are aware of this lurking danger. Just like bacteria, these minute lifeforms are becoming resistant to the handful of treatment options.

Prof Carlien Pohl-Albertyn from the Department of Microbiology and Biochemistry at the University of the Free State is the NRF SARChI Research Chair in Pathogenic Yeasts. She and her team at the university are studying this neglected field, which annually claims the lives of 1,7 million people worldwide. It is estimated that over 3,2 million South Africans are afflicted by fungal diseases each year.  http://www.samj.org.za/index.php/samj/article/view/12753

Prof Pohl-Albertyn explains that all these pathogenic yeasts are opportunistic pathogens, which cause disease when the immune system is under pressure. The following people are at risk:

•    people who have spent a long time in an intensive care unit;

•    people who have a central venous catheter;

•    people who have a weakened immune system, for example, people on cancer chemotherapy, people who have had an organ transplant, and people with low white blood cell counts;

•    people who have recently had surgery, especially multiple abdominal surgeries;

•    people who have recently received lots of antibiotics in hospital;

•    people who receive total parenteral nutrition (food through a vein);

•    people who have kidney failure or are on haemodialysis;

•    people with diabetes;

•    pre-term babies;

•    people who inject drugs.

But what is the difference between a pathogenic fungus or yeast that causes disease, and the harmless yeast we use to make sourdough?  Fungi, except for mushrooms, are microscopic organisms and include yeasts, such as baker’s yeast. Yeasts are just unicellular fungi. The vast majority of fungi are not pathogenic (disease causing) and live in the environment, in soil, on plants, in water, on food – think of bread mould. They even float around in the air that we breathe. Many are helpful and are used to prepare various foods such as bread, beer, wine, blue cheese, camembert and brie, coffee, chocolate, tofu, soy sauce and even sake.

The original source of antibiotics

The well-known fungus, Penicillium, was the original source of antibiotics. Fungi also make up part of our microbiome, which is all the micro-organisms that we carry on our skin, in our mouth, lungs, and in our gut. Under normal circumstances, these microbes do not cause harm, and in fact, we cannot survive without our microbiome.

“A pathogenic fungus will break down the skin or mucosal cells in your body by secreting enzymes that can break down cells. These break-down products are used as food by the fungus. Once inside the bloodstream, it is swallowed by white blood cells. If the fungus survives inside the white blood cells or is able to break open the white blood cells, it can travel to any of your organs, where it will grow inside the organ, damaging it as it did with the cell or mucosal membranes. People with compromised immune systems are especially vulnerable,” she says.

Some of these pathogenic yeasts are inhaled and can pass from the lungs into the bloodstream, where they are taken up by white blood cells. If they are not killed by the white blood cells, they can hide in these cells and infect different organs, such as the brain and kidneys. An example of a disease-causing yeast that infects the brain is Cryptococcus neoformans. It causes cryptococcal meningitis and death in 10-15% of HIV-positive patients.

This yeast has a thick layer around it, called a capsule. The capsule protects the yeast against white blood cells.

Students in the research group are investigating the composition of this capsule. They are trying to understand how certain molecules, including fatty acid metabolites in the capsule, help the yeast to protect itself.

Other yeasts, such as Candida albicans, are part of the microbiome where they normally do not cause any problems, but when a person’s immune system is compromised, the yeast has the ability to form filaments that can penetrate between the human cells to reach the bloodstream. From there, this yeast can also infect many organs, including the lungs, heart, liver, kidneys, joints, and brain.

The most common infectious Candida species is Candida albicans, and in South Africa it is followed closely by Candida parapsilosis and Candida glabrata. Other less common species are Candida tropicalis, Candida dubliniensis, Candida auris, and Candida krusei.

New yeast species

Candida auris is a new yeast species that was first identified 11 years ago in a hospital patient in Japan. Since then, it has spread to more than 30 countries, including South Africa, causing outbreaks in hospitals around the world. It is inherently resistant to fluconazole (a commonly used drug) and has also shown the ability to become resistant to the other classes of antifungal drugs available. “Very little is known about this yeast, but one theory is that it is an environmental yeast that may have been transferred to people via birds, and that climate change may have played a role in the emergence,” Prof Pohl-Albertyn says.

Common yeast infections are infections of the mucous membranes, such as vaginal infections and oral infections, as well as skin infections, such as athlete’s foot, jock itch, and ringworm. The symptoms of these superficial infections are irritation, itching, pain, redness. The symptoms of fungal bloodstream infections are often non-specific and include fever and chills. They are much more difficult to diagnose and require culturing a blood sample or a biopsy to identify the specific organism.

Treatment is problematic

Treatment is highly problematic because there are only three types of antifungal drugs available. Some of the fungi are inherently resistant to the drugs and adding to that, resistance increases. The really effective treatments also have nasty side effects.

In Prof Pohl-Albertyn’s laboratory, the team investigates various aspects of the functioning of the yeasts and fungi in order to find possible new treatments, as well as repurposing drugs already approved for other conditions, which can be used in combination with antifungal drugs.

“We also study the role of fatty acids and their metabolites in the interaction between the yeasts and the host. These fatty acid metabolites are signals that can either cause or resolve inflammation in the host. They are produced by both the host and the yeast and are known to play an important role in host tissue damage, immune response, as well as enabling colonisation of the gastrointestinal tract by Candida albicans.

“Our lab also studies the interaction between Candida species and another opportunistic pathogen, the bacterium Pseudomonas aeruginosa. The reason for this is that many infections are not caused by only one organism, but by both together – so we need to understand how they influence each other and how the combination influences the host,” she says.

Best gene editing technology

At the UFS, the team also uses the best gene editing technology in the world, called CRISPR.

“We use it in two ways: It can be used to delete genes in an organism. We can then compare the mutant strain with the original strain to see what the role of the specific gene is. We can also use it to add a fluorescent marker to a gene. The protein made by this gene will then fluoresce under a certain light wavelength and we can see where in the cell the protein is and also how much of the protein is being made by the cell. These techniques are all used to study the function of specific proteins related to the virulence and resistance in the yeasts.

However, biochemically speaking, fungi are very similar to humans, so anything that damages fungal cells may also damage human cells. We are on the same branch of the tree of life, the Eukaryotes. This research takes grit, long-term endurance, and lots of funding.