Pan-azole- and multi-fungicide-resistant Aspergillus fumigatus is widespread in the United States

• Published in: Applied and environmental microbiology 2024-04, Vol.90 (4), p.e0178223
• Main Authors: Celia-Sanchez, B N, Mangum, B, Gómez Londoño, L F, Wang, C, Shuman, B, Brewer, M T, Momany, M
• Format: Article
• Language: English
• Subjects: Antifungal Agents - pharmacology; Aspergillus fumigatus; Azoles; Azoles - pharmacology; Drug resistance; Drug Resistance, Fungal - genetics; Drugs; Environmental Microbiology; Fungal Proteins - genetics; Fungi; Fungicides; Fungicides, Industrial - pharmacology; Gene flow; Heterocyclic compounds; Humans; Microbial Sensitivity Tests; Pathogens; Pesticides; Phylogeny; United States
• ISSN: 0099-2240; 1098-5336; 1098-5336
• DOI: 10.1128/aem.01782-23

is an important global fungal pathogen of humans. Azole drugs are among the most effective treatments for infection. Azoles are also widely used in agriculture as fungicides against fungal pathogens of crops. Azole-resistant has been increasing in Europe and Asia for two decades where clinical resistance is thought to be driven by agricultural use of azole fungicides. The most prevalent mechanisms of azole resistance in are tandem repeats (TR) in the promoter coupled with mutations in the coding region which result in resistance to multiple azole drugs (pan-azole resistance). Azole-resistant has been isolated from patients in the United States (U.S.), but little is known about its environmental distribution. To better understand the distribution of azole-resistant in the U.S., we collected isolates from agricultural sites in eight states and tested 202 isolates for sensitivity to azoles. We found azole-resistant in agricultural environments in seven states showing that it is widespread in the U.S. We sequenced environmental isolates representing the range of U.S. sample sites and compared them with publicly available environmental worldwide isolates in phylogenetic, principal component, and ADMIXTURE analyses. We found worldwide isolates fell into three clades, and TR-based pan-azole resistance was largely in a single clade that was strongly associated with resistance to multiple agricultural fungicides. We also found high levels of gene flow indicating recombination between clades highlighting the potential for azole-resistance to continue spreading in the U.S.IMPORTANCE is a fungal pathogen of humans that causes over 250,000 invasive infections each year. It is found in soils, plant debris, and compost. Azoles are the first line of defense antifungal drugs against . Azoles are also used as agricultural fungicides to combat other fungi that attack plants. Azole-resistant has been a problem in Europe and Asia for 20 years and has recently been reported in patients in the United States (U.S.). Until this study, we did not know much about azole-resistant in agricultural settings in the U.S. In this study, we isolated azole-resistant from multiple states and compared it to isolates from around the world. We show that which is resistant to azoles and to other strictly agricultural fungicides is widespread in the U.S.