What is the deadliest mushroom

When the fungal infection becomes a mortal danger

Every year, more than a billion people worldwide develop fungal infections. Most of these are superficial infections, but around 1.5 million people die every year as a result of an invasive fungal infection - roughly as many as from malaria or tuberculosis. A common cause of these life-threatening infections is the yeast "Candida albicans". For most people, it is a harmless roommate of the mucous membranes. So it belongs to the normal microbiome of the intestine. In exceptional situations, however, the fungus can proliferate unhindered and become a deadly danger for its carrier. When and how exactly this happens, the international research team around the infection biologist Bernhard Hube from the Leibniz Institute for Natural Product Research and Infection Biology in Jena wants to find out. The Federal Ministry of Research supported the scientists in this.

Once the immune system is weakened, Candida albicans can cause infections. Treatment with antibiotics also changes the normal bacterial skin and intestinal flora in such a way that the fungus can multiply. The result is inflammation of the skin or mucous membrane, for example in the genital area or in the mouth. Around three quarters of all women will suffer from a vaginal Candida infection at least once in their life. In extreme situations such as after an intestinal operation, chemotherapy or an organ transplant, the fungi can penetrate deeper into the body and attack internal organs via the blood vessel system. In the worst case scenario, sepsis can be fatal.

How bacteria slow down the fungus

What happens at the molecular level in this process is still largely unexplored. “We are particularly interested in the role of probiotic microbes and their interaction with the fungus,” says microbiologist Hube. For this purpose, the researchers from Jena have developed a special cell culture model on which they can observe the interaction of Candida albicans with lactobacilli. The scientists have now been able to demonstrate in the laboratory that these lactic acid bacteria also have a protective effect on fungal infections.

“How the fungus grows is crucial for the infection process,” says Hube. In the event of a pathological development, Candida albicans increasingly forms so-called hyphae, which, like root arms, bore into the epithelial cells of the skin and mucous membranes and cause massive damage. “In our model, we could see that lactobacilli reduce the growth of the fungi hyphae,” explains Hube. “In addition, infected cells are rejected more quickly under the action of the bacteria, so that the entire tissue remains intact.” The results suggest that targeted, personalized treatment with probiotics could offer protection against invasive fungal infections for particularly vulnerable patient groups.

Fungal poison destroys the host cell membrane

In addition, the researchers have solved another mystery surrounding Candida albicans: They have discovered a fungal toxin that plays a key role in its activity as a dangerous pathogen. Candidalysin, the name of the poison, perforates the membrane of the host cells and ultimately destroys them. The researchers had hoped to be able to counteract this with active ingredients that neutralize the toxin. Unfortunately, it's not that simple. When the toxin is released, the fungus activates the body's immune system. The immune cells can attack and eliminate the fungus. Toxin neutralization could therefore also be dangerous because it prevents this immune response.

With vaginal yeast infections, however, the immune system often overreacts, leading to severe inflammation. "The immune cells are attracted by the toxin, are very aggressive and cause great collateral damage without actually being able to do anything against the fungus," says Hube. "If we remove the toxin here, the inflammation will be reduced and the infection contained." Hube and his team are already in contact with companies to develop an appropriate active ingredient.

Finding Biomarkers for Diagnosis

But many questions about the complex interplay between fungus, microbiome and immune system are still open. Finding a biomarker for diagnosing invasive fungal infections is a major challenge. These are often associated with unspecific symptoms such as fever. "The doctors then often think that it is a bacterial infection and use antibiotics," says Hube. “But these decimate the beneficial bacteria in the microbiome, and the fungus can spread even more. If we could find a reliable biomarker that could differentiate between a harmless colonization of Candida albicans and a pathological infestation, it would be of great help for both doctors and patients. "


Contact Person:

Prof. Dr. Bernhard Hube
Leibniz Institute for Natural Product Research and Infection Biology
Hans Knöll Institute Jena
Beutenbergstrasse 11A
07745 Jena
[email protected]