Land use drives drug resistance in an airborne human fungal pathogen.

Humans are exposed to the mold Aspergillus fumigatus via inhalation, and infections are increasingly resistant to triazole-class antifungals. Ecologically, this fungus is a ubiquitous saprotroph found in terrestrial environments. Although triazole-resistant A. fumigatus is found in large quantities in specific agricultural environments, it is not clear how much these contribute to the overall exposure of individuals to antifungal resistance. Triazoles are also used to protect a wide range of products unrelated to agriculture, and therefore, it could not be excluded that the resistance observed in agricultural settings may be the result of selection beyond agricultural sources. In the case of A. fumigatus, genomics cannot reliably link resistant isolates to specific environmental sources. Therefore, we used a spatial sampling approach to measure population trends in triazole resistance. We conducted a large-scale, unbiased air sampling throughout the Netherlands using a citizen science approach. We find that $\sim $4$\%$ of over 60K screened colonies are resistant to clinical triazoles. Modeling resistance data with spatial land-use data shows that agricultural land use, particularly flower bulbs and greenhouses, can predict peaks in antifungal resistance in airborne A. fumigatus in the Netherlands. Furthermore, genotyping resistant isolates suggests land-use-associated niche differentiation between two dominant resistance haplotypes, with only one of the two showing a significant association with agricultural land use. By linking triazole resistance to land use, this work informs necessary policy-driven changes to reduce human exposure to antifungal-resistant A. fumigatus, and suggests that similar spatial patterns in antifungal resistance may occur in other agriculture-associated fungi as well.