Evidence for the agricultural origin of antimicrobial resistance in a fungal pathogen of humans

Resistance to clinical antimicrobials is an urgent problem, reducing our ability to combat deadly pathogens of humans. Azole antimicrobials target ergosterol synthesis and are highly effective against fungal pathogens of both humans and plants leading to their widespread use in clinical and agricultural settings. The fungus Aspergillus fumigatus, causes 300,000 life-threatening infections in susceptible human hosts annually and azoles are the most effective treatment. Resistance to clinical azole antifungals has become a major problem in Europe and India over the last decade, where identical mutations in cyp51A, an ergosterol biosynthetic gene, have been found in strains from both clinical and agricultural settings. Shared cyp51A genotypes suggest that clinical azole resistance might have had an agricultural origin; however, until now, independent origins of clinical and agricultural mutations could not be ruled out. Here we show that azole-resistant isolates of A. fumigatus from clinical and agricultural settings also carry mutations conferring resistance to quinone outside inhibitor (QoI) fungicides, which are used exclusively in agricultural settings. This is the first report of a clear marker for the agricultural origin of resistance to a clinical antifungal. We anticipate that our work will increase the understanding of interactions between pathogens of plants and pathogens of humans.