Study: Better to treat life-threatening fungal infections in the future

Deadly fungal infections avoidable thanks to new treatment method?
Fungal infections are a common symptom, although they can appear in very different forms. They often show up as infections of the skin, such as athlete's foot. But a fungal infection can also spread in the body and in the worst case cause blood poisoning (sepsis). Around 1.5 million people worldwide die each year from a corresponding fungal sepsis, according to the information from the Medical University of Vienna (MedUni Vienna). Here, the therapeutic options could be significantly improved in the future by a new discovery and numerous lives could be saved, reports the MedUni Vienna.

Scientists at the IMBA (Institute of Molecular Biotechnology) and the Max F. Perutz Laboratories (MFPL) at MedUni Vienna and the University of Vienna have successfully identified a completely new mechanism that could make it possible to treat life-threatening fungal infections in the future. By blocking the enzyme CBL-B, the immune defense against the fungal pathogen Candida albicans is significantly increased, the scientists report in the journal "Nature Medicine" of their current study results.

Invasive fungal infections often end in death
According to MedUni Vienna, fungal infections are "among the most common infections worldwide" and every fourth person "suffers from unpleasant skin or mucous membrane infections in the course of his life." As a rule, an infection with the unicellular yeast Candida albicans is harmless and can be avoided to treat well. However, these are not the only forms that a fungal infection can take. Because a weakened immune system does not recognize the pathogen in time, the fungus can spread throughout the body and cause life-threatening blood poisoning and massive organ damage, reports the MedUni Vienna. According to the experts, these so-called invasive infections are approximately 40 percent fatal and lead to around 1.5 million deaths per year.

Lack of antifungal therapy options
According to MedUni Vienna, fungal infections play an increasingly important role in everyday medical life, especially in patients whose immune systems are weakened. "Longer stays in hospitals but also many new treatments in modern medicine, such as organ transplants or tumor therapies, are often associated with a short to long-term weakening or even damage to the immune system," the university said. In this weakened condition, an infection with the widespread yeast Candida albicans could quickly become life-threatening. Not only does the diagnosis of corresponding infections pose problems, but treatment is also extremely difficult given the lack of effective antifungal treatment options for infections at this advanced stage.

Immune response to Candida albicans decoded
The Vienna research team was not only able to demonstrate in its current studies how the immune system successfully defends itself against an invasion of Candida albicans. They also developed a protein that can be used against the invasive Candida infection. The human immune system has the task of unmasking intruders, whereby viruses, bacteria but also fungal pathogens are identified by so-called "immunoreceptors" based on a typical signature on the outer cell wall, the scientists explain. The researchers report that these immunoreceptors dock onto the outside wall of the pathogen, which alarms and activates the body's own defense cells, which then kill the pathogen.

Enzyme CBL-B vitally important
According to the findings of the research team around the molecular biologists Gerald Wirnsberger and Florian Zwolanek from the work groups of Josef Penninger (IMBA) and Karl Kuchler (MFPL), the enzyme CBL-B and a signal transmitter called SYK play a special role in the immune response against Candida infections . Here, SYK works with the immune receptor on the cell surface and passes on “the signal for the targeted defense against the fungal pathogen, while CBL-B slows down the signal transmission for the immune response and finally switches it off by destroying SYK,” according to MedUni Vienna . The researchers therefore developed a completely new protein, a so-called “inhibitor”, with which they were able to specifically block CBL-B in mice. In the subsequent experiments, the protein was successfully used to ward off an invasive Candida infection, while mice in which CBL-B was active succumbed to systemic Candida infection within a short period of time, the scientists report. This opens up a new path to therapy against invasive fungal infections.

Milestone in the treatment of invasive fungal infections
According to Karl Kuchler (MFPL), the research results are “a first milestone in a completely new type of treatment for Candida albicans.” For the first time, the immune response that is modulated by CBL-B has been successfully targeted. "This innovative therapy method could prove to be very clinically successful, especially in combination with existing therapy methods in which only the growth of the fungi can be blocked," emphasizes the expert. Josef Penninger, scientific director of the IMBA, was equally optimistic. “It will become increasingly important for the medicine of tomorrow to decipher the molecular puzzles of the immune system in order to be able to strengthen this body's protective shield against a certain intruder. We have now succeeded in doing this with the often fatal Candida albicans mushroom, ”Penninger concludes. (fp)

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