Antifungal resistance development in a human pathogenic fungus

Each year, about 50 people in the Netherlands die due to an infection with the fungus Aspergillus fumigatus that is resistant to medical azoles. Currently, there are no alternatives with similar efficacy as azoles for controlling aspergillus disease.

Azoles also represent a main class for crop protection and thus have a major role in global food production. It is therefore crucial to preserve this class for medical treatment without impairing agricultural practices. Evidence is mounting that resistance to medical azoles is a side effect of environmental azole fungicide use, as identical resistance mutations, characterized by a unique combination of genetic changes, are observed in environmental and clinical isolates. Recent insights indicate that plant waste containing azole fungicide residues are “hotspots” for resistance development. However, it is unknown how azole resistance mutations have evolved and how possible fitness costs are overcome.


Given the continued emergence of new resistance mutations in “hotspots” and the rapid global spread of azole-resistant A. fumigatus, this non-durable situation urgently needs fundamental research which results shall be the basis for effective interventions. The overall goal of my research is to understand selection and evolution of azole resistance in A. fumigatus.


I am addressing Where, When and How azole-resistance evolves in A. fumigatus, and I have defined the following key objectives; To determine the environmental niches of A. fumigatus and its characteristics and the frequency for (a)sexual and parasexual reproduction in these niches (Where). To investigate how the mode of reproduction affects the generation of genotype diversity in relation to the evolution of azole-resistance in A. fumigatus (When). And finally, to provide evidence that antifungal compounds can select for specific mutations that underpin azole-resistance in A. fumigatus (How).

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