Project
Antifungal resistance in Aspergillus fumigatus
Aspergillus fumigatus is a fungus that can cause severe illness in a growing group of immunocompromised individuals. Treatment with antifungal medicine more frequently fails due to increasing levels of antifungal resistance in A. fumigatus. In the Netherlands, it has been established that the environment is a primary source of this resistance due to the environmental application of antifungals, for example as pesticides in agriculture. I study how this antifungal resistance arises and spreads through the environment.
Background
The air we breathe is contains fungal spores, produced by fungi as a mode of reproduction. Although we can inhale up to a hundred spores every day, these spores are harmless to most of us as our immune system can remove them from our lungs before they can grow and cause serious infection. There are patients however, whose immune system is weakened or suppressed and they are at risk for fungal infection. Luckily, we can treat most fungal infections with a class of antifungal medication called azoles. But treatments with these azoles fail more and more often because fungi have become resistant to them. Meaning that the treatment with azoles doesn’t stop these fungi from growing. Key here is that many types of antifungals are not just used as medication but also as pesticides in agriculture, and other environmental applications. This causes pathogenic fungi to become cross-resistant to medications they may have never been in contact with.
The most notable of these pathogenic fungi is called Aspergillus fumigatus. This fungus normally grows in heaps of dead plant material we make for composting in our gardens, or those made at an industrial scale in agriculture. It thrives at the high temperatures these heaps reach during the composting process. It is in these plant waste heaps where Aspergillus fumigatus encounters antifungal pesticides. In these heaps containing high concentrations of azoles we find a high percentage of azole-resistant Aspergillus fumigatus growing in very large numbers, which is why we refer to them as resistance hotspots.
Project description
The focus of my project is on the ecology and evolution of triazole resistance in Aspergillus fumigatus. How does selection for triazole resistance takes place in resistance hotspots, and how does it persist outside of the hotspots where there is less or no selection pressure? To better understand the aerial dispersal of resistant A. fumigatus spores and the resulting health risks caused by their inhalation I am also working on the improvement and standardization of environmental air sampling methods. Improving these methods will allow is to ask fundamental questions such as: Are there spatial and temporal differences in aerial resistance levels? Because airborne spores form the most direct health risk, monitoring them will be a powerful tool in effectively addressing the issue.