Search for cause of resistance in Aspergillus fumigatus

Search for cause of resistance in Aspergillus fumigatus

How can the fungus Aspergillus fumigatus become resistant? The answer to that question is of vital importance to people with weakened immune systems. There may be clues to be found in the agricultural use of fungicides. For this reason, researchers from Plant Research International and the St. Radboud University Medical Centre in Nijmegen are working closely together.

Aspergillus fumigatus is a fungus which can occur anywhere indoors and outdoors and can cause infections in people with weakened immune systems.Tissue aspect of an invasive aspergillosis. Localised deviations surrounded by signs of bleeding.
Aspergillus fumigatus is a fungus which can occur anywhere indoors and outdoors and can cause infections in people with weakened immune systems.Tissue aspect of an invasive aspergillosis. Localised deviations surrounded by signs of bleeding.
Normally, these can be successfully treated with anti-fungal agents. But increasingly, Aspergillus strains are proving to be resistant to these fungicides.
The fact that fungi can become resistant to fungicides is well established in agriculture. This can be explained by the often intensive use of those fungicides in, for example, bananas and wheat. However, in human medicine, the use of anti-fungal agents is so low that the development of resistance in patients virtually does not occur. The selection pressure which is leading to resistant Aspergillus strains is therefore coming from somewhere else.

Resistant strains

The researchers discovered that a proportion of the Aspergillus strains they had collected from various sources were indeed resistant. They then tested whether the strains found were resistant to thirty agricultural fungicides and to medicines containing comparable substances. This proved to be the case for five fungicides.
The researchers also looked at the interaction between the fungi and the active substances in the fungicides. The gene of the fungicides codes for a protein with a three-dimensional structure, to which the active substance of the fungicide attaches. The five fungicides were the only ones that fitted exactly, which is a further indication that Aspergillus is under selection pressure in the environment.
But this in itself does not explain how the resistance occurs and which substance causes the change. It could be caused by a fungicide but equally it could be caused by something else because comparable active substances are also widely used in paint, sealants, clothing, and wallpaper glue, and on fences. The proof of which substance and application is causing the selection pressure has not yet been delivered. Our researchers are working together closely with researchers from the St. Radboud University Medical Centre to solve this riddle.

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    Resistance to Aspergillus fumigatus