A slime weapon against fungal infections – wissenschaft.de

Hope in the fight against the infamous candidiasis: Scientists have identified substances in mucosal secretions that can control Candida albicans. Special representatives of the so-called glycans inhibit the development of a normally harmless inhabitant of the mucosa into its harmful form. Scientists have also managed to artificially produce the active ingredients of the mucus. This could lead to the development of a new class of drugs that can replace stubborn pathogens relatively naturally.

The human body is home to a motley community of microbes that normally don’t cause any problems and are even important to our health. However, the microbiome also includes potential bad people – bacteria or fungi that can do harm if they get out of hand. One of such difficult representatives is the yeast Candida albicans, which is found on the mucous membranes of most people. In its spherical form it is trouble-free. But under certain circumstances, the fungus begins to form invasive networks. Through this so-called Then only the chemistry club can help – but there are only a few effective antifungal agents, and they have problematic side effects. Accordingly, there is a need for alternative treatment options.

Traces of mucus

An international team led by Rachel Hevey of the University of Basel and Katharina Ribbeck of the Massachusetts Institute of Technology in Cambridge is currently looking for substances with antifungal properties. The approach of scientists is to make the substances of our natural defense system useful. In the case of mucous membranes, a key role is played by their characteristic: secretion. Studies in the last few years have shown that mucus provides not only physical but also pharmacological protection. There were already indications that the mucus contains active ingredients that counteract the problematic development of Candida. However, it is not known exactly which ingredients are responsible for this effect.

In their research, the researchers focused on a group of special sugar molecules in human mucus that have already been shown to affect certain pathogens. These so-called glycans are the main constituent of mucins, which in turn are responsible for the gel-like texture of the mucus. First, the scientists made it clear through experiments with mucus samples that the secretions can actually inhibit the formation of Candida albicans fibers. They then analyzed the molecular composition of the active mucus samples. They identified over a hundred different glycans with potential antimicrobial activity.

potential for medicine

Of the representatives that were most common in all samples, the team then synthesized six candidates for further analysis. “It is almost impossible to isolate glycans from mucus samples,” explains Hevey. “Therefore, the only way to study their properties in more detail is to synthesize them. But it is an extremely complex chemical process. ‘ However, thanks to a specially developed method for synthesizing these molecules, the team finally managed to artificially replicate glycans and produce them in useful quantities. Scientists were then able to use these substances to test cultures of Candida albicans in the laboratory.

This confirmed that the synthesized glycans were able to suppress fibrosis of the yeast fungus, i.e. change from harmless to infectious. According to the researchers, their work on other bacterial and fungal pathogens also shows that these polysaccharides have significant medical potential. They could therefore become the basis for the development of a new class of drugs. “It is becoming clear that the mucus contains an extensive library of small molecules with many virulence inhibitors against any problematic pathogens that are just waiting to be discovered and used,” says Ribbeck.

The development of drugs against fungal infections is of particular importance, says Hevey: “There is an urgent need for new antifungal agents. For a long time, glycans were thought to be responsible only for the mucosa of mucus. We can now see that they can actually pave the way for new, much-needed drugs against these problematic pathogens. ‘ Scientists will continue to work towards this goal. Among other things, they are currently looking for ways to bring glycans to different areas of the body.

Source: University of Basel, Research Paper: Nature Chemical Biology, doi: 10.1038 / s41589-022-01035-1

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