Azole resistance mechanisms and population structure of Aspergillus fumigatus on retail plant products

<p><em>Aspergillus fumigatus </em>is a ubiquitous saprotroph and human-pathogenic fungus that is life-threatening to the immunocompromised. Triazole-resistant <em>A. fumigatus</em><em> </em>was found in patients without prior treatment with azoles, leading researchers to conclude that resistance had developed in agricultural environments where azoles are used against plant pathogens. Previous studies have documented azole-resistant <em>A. fumigatus </em>across agricultural environments, but few have looked at retail plant products. Our objectives were to determine if azole-resistant <em>A. fumigatus </em>is prevalent<em> </em>in retail plant products produced in the United States (U.S.), as well as to identify the resistance mechanism(s) and population genetic structure of these isolates. Five hundred twenty-five isolates were collected from retail plant products and screened for azole resistance. Twenty-four isolates collected from compost, soil, flower bulbs, and raw peanuts were pan-azole resistant. Resistant isolates had the TR₃₄/L98H, TR₄₆/Y121F/T289A, G448S, and H147Y <em>cyp51A </em>alleles, all known to underly pan-azole resistance, as well as  WT alleles, suggesting that non-cyp51A-mechanisms contribute to pan-azole resistance in some isolates. Minimum spanning networks showed two lineages containing isolates with TR alleles or the F46Y/M172V/E427K allele, and discriminant analysis of principle components (DAPC) identified three primary clusters. This is consistent with previous studies detecting three clades of <em>A. fumigatus</em> and identifying pan-azole-resistant isolates with TR alleles in a single clade. We found pan-azole resistance in U.S. retail plant products, particularly compost and flower bulbs, which indicates the risk of exposure to these products for susceptible populations and that highly resistant isolates are likely distributed worldwide on these products.</p>