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Viruses and bacteria frequently manage to infect the human body. The corona epidemic provides further terrifying proof of this. We don’t need to be so ‘scared of fungi. At least not yet, because fungal infections are still learning how to invade the human immune system. Research by the Westfälische Wilhelms Universität Münster (WWU) provides new insights into how they go about this.

So, fungal infections tend be less dangerous in general. This is because they are easily recognized by the human immune system. Their cells are surrounded by a solid cell wall of chitin (a kind of carbohydrate) and other complex sugars. So to speak, chitin is the alarm signal for the immune system. And the immune system invariably reacts to chitin with a whole arsenal of defensive weapons.

Enzymes for the defense system

Except that the unfortunate thing is that some fungi have learned to avoid these counterattacks before being fatally recognized. They possess certain enzymes (chitosan deacetylase) that enable them to modify some of the chitin building blocks. This creates what’s called chitosan, a biopolymer which is invisible to the immune system.

One of the more aggressive fungi types is the cryptococcus neoformans. This can lead to fatal infections. This fungus has four genes that seem to encode these kinds of enzymes. Up until now, researchers had only been able to determine that three of them are capable of actually altering chitin building blocks. The function of the fourth protein was unknown.

Model of the enzyme chitosan deacetylase with the chitosan pictured in the middle in green.

Scientists from the WWU have now examined this fourth enzyme in detail and discovered that the enzyme is a chitosan deacetylase that had not been previously defined. The study was published in the scientific journal PNAS (Proceedings of the National Academy of Sciences).

E-coli bacterium

Researchers led by Professor Bruno Moerschbacher of the Institute of Plant Biotechnology and Biology at WWU developed biotechnological methods for the introduction of such genes into the E. coli bacterium. They were also able to characterize in detail the enzymes produced in this bacterium.

“Apparently, the chitin dacetylases need several chitin building blocks in succession in the chain in order to be able to attack the molecule and remove an acetic acid,” biochemist Moerschbacher explains. “That’s why there are always some chitin building blocks left over at the end. The new chitosan deacetylase is therefore able to effectively remove these last acetic acid molecules.”

New medicines

The idea that it was only this last step that made the fungus really invisible to the human immune system was obvious. And sure enough: in collaboration with dermatologists from the University Medical Center Hamburg-Eppendorf, researchers were able to establish that a chitosan, which still contains many acetic acid molecules, stimulates the immune system even more effectively than chitin does. The only way to produce a product that no longer activates the immune system is to treat it with chitosan deacetylase.

Chitosan deacetylase is therefore a crucial agent used by a fungus to attack its host under the chitin-radar. Complete removal of the acetic acid molecules from the chitin acts as a kind of magic cape, rendering the fungus invisible to the immune system. “This makes chitosan deacetylase an interesting target for new drugs,” emphasizes Christian Gorzelanny from the University Medical Center Hamburg-Eppendorf.