Abstract
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 share the same molecular target as 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 azole 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 fungicide application. We observed a reduction in the abundance of A. fumigatus on fields following fungicide treatment in 2017, a finding that was not observed on an organic control field with only natural plant protection agents applied. However, this finding was less pronounced during our 2018 sampling, indicating that the impact of fungicides on A. fumigatus population size is variable and influenced by additional factors. The overall resistance frequency among agricultural isolates is low, with only 1 to 3% of isolates from 2016 to 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 alterations in antifungal susceptibility, fungicide 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 in this context.IMPORTANCE Antibiotic resistance is an increasing threat to human health. In the case of Aspergillus fumigatus, which is an environmental fungus that also causes life-threatening infections in humans, antimicrobial resistance is suggested to arise from fungicide use in agriculture, as the chemicals used for plant protection are almost identical to the antifungals used clinically. However, removing azole fungicides from crop fields threatens the global food supply via a reduction in yield. In this study, we survey crop fields before and after fungicide application. We find a low overall azole resistance rate among agricultural isolates, as well as a lack of genomic and population impact following fungicide application, leading us to conclude azole use on crops does not significantly contribute to resistance in A. fumigatus.
Highlights
Antibiotic resistance is an increasing threat to human health
The median MICs remained unchanged, indicating that the majority of the population following azole exposure does not exhibit a change in MIC. These results indicate that the rate of resistance to clinical azoles among environmental A. fumigatus organisms isolated from agricultural environments is low overall and that exposure to agricultural azoles alone or in combination with other fungicides causes a minor increase in MIC values for some of the population, but the majority of isolates are left unchanged
The use of azole fungicides for plant protection has been previously suggested as a driver of clinical resistance in the environmental saprobe and human pathogen A
Summary
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 share the same molecular target as the frontline antifungals used clinically. We find a low overall azole resistance rate among agricultural isolates, as well as a lack of genomic and population impact following fungicide application, leading us to conclude azole use on crops does not significantly contribute to resistance in A. fumigatus. This must be balanced against the need to preserve the activity of the azoles for clinical use, and, as such, there is an urgent need to identify the contributions of azole fungicide use on food crops to the development of resistance in A. fumigatus We address this through systematic soil sampling conducted on 10 agricultural sites in Germany over a 3-year period, including conventionally managed fields applying azoles fungicides as well as those practicing organic agriculture that do not use these compounds. In the largest published A. fumigatus sequencing effort to date, and the first to focus on the fungus in its natural niche, we use whole-genome sequencing (WGS) to examine the impact of azole fungicides on the population genetics of 64 agriculturally isolated A. fumigatus isolates
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