Aspergillus fumigatus is a globally distributed fungal pathogen that can infect humans and is commonly found in the environment. Azole antifungals are the primary treatment for A. fumigatus infections; however, the emergence of azole resistance has become an important public health issue. This resistance is often linked to the use of agricultural fungicides and is primarily caused by tandem repeats (TRs) in the cyp51A promoter, along with mutations in the coding region, leading to pan-azole resistance. Azole-resistant A. fumigatus has been identified in patients across the United States and has been found in environmental soil samples from 38 states. A previous study conducted in the southeastern United States detected azole-resistant A. fumigatus in the environment. To further investigate the persistence of these resistant strains, soil samples were collected over three time periods. Whole genome sequencing was performed on isolates from each sampling date, and results were compared to publicly available isolates using phylogenetic, principal component, and ADMIXTURE analyses. These findings demonstrated that the same strains of TR-based azole-resistant A. fumigatus persisted in the same environmental hotspot over time. Additionally, we observed high levels of recombination between different clades, which may contribute to the ongoing presence of A. fumigatus in the United States. These findings highlight the environmental persistence of azole-resistant strains and underscore the need for monitoring antifungal resistance in environmental settings to better understand its potential clinical implications.IMPORTANCEAspergillus fumigatus is a fungal pathogen that poses a substantial threat to humans, particularly in high-risk populations, with mortality rates reaching 90%. It is also a saprophyte that is commonly found in agricultural settings. Azoles are the primary antifungal treatment for A. fumigatus infections; however, azole-resistant strains have emerged, particularly in Europe and Asia, over the past two decades. Recently, such strains have also been isolated from clinical cases in the United States and identified in environmental soil samples from 38 states. In this study, azole-resistant A. fumigatus was isolated with three different variants of tandem repeat mutations in the cyp51A promoter region from southeastern U.S. soil samples collected over three time periods. These findings demonstrate that resistant strains can persist in the environment for at least 12 months, suggesting that established environmental hotspots can serve as ongoing reservoirs for resistant strains.
Celia-Sanchez et al. (2026) studied this question.