Azole use in agriculture reduces Aspergillus fumigatus abundance but does not alter its population structure

Antibiotic resistance is an increasing threat to human health. In the case of Aspergillus fumigatus, which is both an environmental saprobe and an opportunistic human fungal pathogen, resistance is suggested to arise from fungicide use in agriculture, as the azoles used for plant protection are almost identical to the frontline antifungals used clinically. However, limiting azole fungicide use on crop fields to preserve their activity for clinical use could threaten the global food supply via a reduction in yield. In this study we clarify the link between fungicide use on crop fields and resistance in a prototypical human pathogen through systematic soil sampling on farms in Germany and surveying fields before and after azole application. We observe a reduction in the abundance of A. fumigatus on fields following azole treatment - a finding that was not observed on an organic control field not applying azoles. However, the overall resistance frequency among agricultural isolates is low, with only 1-3% of isolates from 2016-2018 displaying resistance to medical azoles. Isolates collected after the growing season and azole exposure show a subtle, but consistent decrease in susceptibility to medical and agricultural azoles. Whole genome sequencing indicates that, despite the decrease in fungal abundance, azole application does not significantly affect the population structure and genetic diversity of A. fumigatus in fields. Given the low observed resistance rate among agricultural isolates, as well the lack of genomic impact following azole application, we do not find evidence that azole use on crops is significantly driving resistance in A. fumigatus.