Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus

Azole resistance in Aspergillus fumigatus is on the rise. Nontarget-mediated mechanisms are a common cause of azole resistance in chronic pulmonary aspergillosis (CPA). Here, we investigate resistance mechanisms using whole-genome sequencing. Sixteen azole-resistant A. fumigatus isolates from CPA were sequenced to assess genome rearrangements. Seven out of 16 CPA isolates showed genomic duplications compared to zero out of 18 invasive isolates. Duplication of regions, including cyp51A, increased gene expression. Our results suggest aneuploidy as an azole resistance mechanism in CPA. Azole resistance in Aspergillus fumigatus is on the rise. Nontarget-mediated mechanisms are a common cause of azole resistance in chronic pulmonary aspergillosis (CPA).

Automated summary

Azole resistance in Aspergillus fumigatus is increasing, and non-target-mediated mechanisms contribute to resistance in chronic pulmonary aspergillosis (CPA). This study used whole-genome sequencing to investigate resistance mechanisms. Sixteen azole-resistant A. fumigatus isolates from CPA were sequenced, and genome rearrangements were assessed. Among them, seven CPA isolates showed genomic duplications, including the cyp51A region, which led to increased gene expression. Our findings suggest that aneuploidy is a resistance mechanism in CPA.