Have we forgotten fungal infections?

Killer fungal infections causing 1.7M deaths a year

Professor of FungiProf Carlien Pohl-Albertyn (right) 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.  

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:

  • those spening a long time in an intensive care unit;
  • presence of a central venous catheter;
  • 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;
  • recent surgery, especially multiple abdominal surgeries;
  • recently received lots of antibiotics in hospital;
  • receiving total parenteral nutrition (food through a vein);
  • kidney failure or patients on haemodialysis;
  • diabetes patients;
  • pre-term babies;
  • people who inject drugs. 

What is the difference between baker's yeast and a killer fungus?

EM of yeast buddingWhat is the difference between a pathogenic fungus or yeast that causes disease, and the harmless yeast we use to make sourdough? 

Pic; Yeast buddy or budding?

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 happily live all around us in the soil, on plants, in water, on food – becoming moulds when left too long. They even float around in the air that we breathe. We often use yeasts to prepare various foods such as bread, beer, wine, blue cheese, marmite, camembert and brie, coffee, chocolate, tofu, soy sauce and even to produce dugs such as penicillin.

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 any harm at all, and in fact, we cannot survive without them in - and as a totally natural part of our microbiome.

Good yeast gone bad

However, in someone who is immune-compromised in some way, or has a sugar imbalance can provide conditions for the fungus to become pathogenic (disease causing). A pathogenic fungus will break down the skin or mucosal cells in your body by secreting enzymes that can break down cell walls. The subsequent break-down products are used as food by the fungus. If the fungus gains access to the bloodstream, it is phagocytosed (swallowed) by 'hunter-killer' white blood cells. However, if the fungus can survive inside the white blood cells or is even able to break open the white blood cell, it can travel to any of your organs, where it will grow inside the organ.

Cryptococcal meningitis and the yeast capsule

Sometimes 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. 

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

Invasive filaments

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. 

Common yeast species

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 tropicalisCandida dubliniensis, Candida auris, and Candida krusei.

New yeast species from Japan

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.

Prof Pohl-Albertyn says, “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.”

Common yeast infections

Common yeast infections often affect the mucous membranes, such as vaginal infections (thrush) 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 the culturing of a blood sample to detect the yeast or a biopsy to identify the specific organism.

Effective treatments for yeast infections are 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. Furthermore, the really effective treatments also have nasty side effects. Finding effective treatments for fungal infections is a major challenge. In some respects, fungi are very similar to humans, so anything that damages fungal cells may also damage human cells.

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 re-purposing 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". 

EM of Candida and Pseudomonas aeroginosaWhen yeast and bacteria join forces

“Our lab also studies the interaction between Candida species and another opportunistic pathogens, 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".

Relating to the abdomen, which is the region of the body between the chest and the pelvis. Full medical glossary
Medication to treat infections caused by microbes (organisms that can't be seen with the naked eye), such as bacteria. Full medical glossary
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A group of organisms too small to be seen with the naked eye, which are usually made up of just a single cell. Full medical glossary
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Abnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. Full medical glossary
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The basic unit of all living organisms. Full medical glossary
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A disorder caused by insufficient or absent production of the hormone insulin by the pancreas, or because the tissues are resistant to the effects. Full medical glossary
A protein that speeds up chemical reactions in the body without being used up itself. Full medical glossary
One of the three main food constituents (with carbohydrate and protein), and the main form in which energy is stored in the body. Full medical glossary
The raising of the body temperature above norma, which may be accompanied by symptoms such as shivering, headache and sweating. Full medical glossary
A viral infection affecting the respiratory system. Full medical glossary
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A treatment for renal failure in which the blood is filtered outside the body to remove toxic substances that would normally be processed by the kidneys Full medical glossary
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An animal or plant that supports a parasite. Full medical glossary
The organs specialised to fight infection. Full medical glossary
Invasion by organisms that may be harmful, for example bacteria or parasites. Full medical glossary
The body’s response to injury. Full medical glossary
relating to the intestines, the digestive tract between the stomach and the anus Full medical glossary
An element present in haemoglobin in the red cells. Full medical glossary
One of two bean-shaped organs that are located on either side of the body, below the ribcage. The main role of the kidneys is to filter out waste products from the blood. Full medical glossary
A large abdominal organ that has many important roles including the production of bile and clotting factors, detoxification, and the metabolism of proteins, carbohydrates and fats. Full medical glossary
Inflammation of the membranes covering the brain and spinal cord, due to infection Full medical glossary
Membranes that line many body structures such as the respiratory tract and the gastrointestinal tract and produce mucus. Full medical glossary
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Having a general effect. Full medical glossary

  A bacterium, virus, or other microorganism that can cause disease.

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A craving to eat non-food substances such as earth or coal. Full medical glossary
Compounds that form the structure of muscles and other tissues in the body, as well as comprising enzymes and hormones. Full medical glossary
A species of rod-like bacteria that live in soil and decomposing matter. Full medical glossary
The ability of a microbe, such as a type of bacteria, to resist the effects of antibiotics or other drugs. Full medical glossary
A microbe, such as a type of bacteria, that is able to resist the effects of antibiotics or other drugs. Full medical glossary
septic arthritis Full medical glossary
A common yeast infection of the vagina. Full medical glossary
A common name for the fungal infection candidiasis. Full medical glossary
A group of cells with a similar structure and a specialised function. Full medical glossary
The muscula passage, forming part of the femal reproductive system, between the cervix and the external genitalia. Full medical glossary
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A type of blood cell that protects the body against foreign substances and produces antibodies. Full medical glossary