New discoveries about deadly fungi – perhaps key to treatment

Aspergillus fumigatus growing on petri dishes. Credit: Jan-Peter Kasper, University of Jena

Aspergillus fumigatus kills as many people as malaria and tuberculosis, but is less well known. It is found everywhere, for example in the ground or in our compost, but it is usually not dangerous to healthy people.

Those who die from it often have a poor immune system or are hospitalized for lung infections, such as COVID-19.

Aspergillus is also a growing problem in agriculture because the fungus causes deadly infections in both plants and animals. In the same way that many bacteria are resistant to antibiotics, this fungus is now becoming increasingly resistant to a limited repertoire of treatments. Therefore, it is important to find new ways to fight fungal infections.

Researchers at the Department of Biomedicine of the UiB School of Medicine, together with researchers from the Faculty of Mathematics and Natural Sciences and the German research team, discovered the enzyme on the surface of the fungus.

The newly discovered enzyme breaks down a vital molecule important for the energy metabolism of cells: the NAD molecule, which is created in our body from vitamin B3.

Without NAD, cells cannot survive. Therefore, the breakdown of NAD could affect immune cells and weaken our immune system in the fight against fungal infection.

Collected old scientific observations

Similar enzymes are found in bacteria that cause infections such as tuberculosis, streptococcus or cholera. The idea that fungi can also have an enzyme that breaks down NAD on their surface was set in the 1950s:

“The activity of the enzyme that breaks down NAD has been detected on the surface of the fungus, but the identity of the enzyme has never been established. However, the fungus is often used in research laboratories and is not known to be pathogenic.” , study leader.

They want to re-examine the hypothesis that an enzyme that degrades NAD may contribute to pathogenic mechanisms in fungi such as Aspergillus fumigatus.

“We measured strong enzyme activity on the surface of the spores from Aspergillus fumigatus. We were surprised,” says researcher and first author Øyvind Strømland.

Modern technology enables the study of enzymes

“Using an elegant biochemical method, we identified fragments of the protein sequence from this enzyme. Since the entire genome of the fungus is known, we could use those fragments to identify the gene encoding the enzyme,” Ziegler says.

“The next step was to use genetic information and create a version of this gene that” trained “laboratory cell lines can produce enough protein for detailed molecular studies,” he continues.

In this way, the researchers were able to study how the enzyme breaks down NAD.

“There are two things that are most important here. Extremely sensitive analytical technology has made it possible to identify enzyme fragments. Another important element is that we now have a genome sequence and can easily identify a gene. That was not possible in the ’50s,” Ziegler said.

He can design new antifungal drugs

The researchers are clear that, although it is known from other diseases that similar bacterial enzymes break down NAD in infected cells, it cannot be said with certainty that this is the case with the enzyme from Aspergillus fumigatus.

However, they now know much more about the enzyme through their research, and it is hoped that this knowledge can help discover new ways to treat fungal infections.

Interestingly, their bioinformatics analyzes revealed that this type of enzyme is predominantly present in pathogenic fungi.

“If we could make a drug with NAD-like molecules, they could block the enzyme in our cells,” the researchers suggest.

A new family of enzymes reveals the Achilles’ heel of fungal pathogens

More information:
Øyvind Strømland et al, Detection of fungal surface NADases that are predominantly present in pathogenic species, Nature Communications (2021). DOI: 10.1038 / s41467-021-21307-z

Provided by the University of Bergen

Citation: New discoveries about the deadly fungus – perhaps the key to healing (2021, March 19) retrieved March 19, 2021 from

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