RRC ID 76734
Author Khateb A, Gago S, Bromley M, Richardson M, Bowyer P.
Title Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus.
Journal Antimicrob Agents Chemother
Abstract 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.
Volume 67(4)
Pages e0125322
Published 2023-4-18
DOI 10.1128/aac.01253-22
PMID 36975834
PMC PMC10112202
MeSH Aneuploidy Antifungal Agents / pharmacology Antifungal Agents / therapeutic use Aspergillosis* / drug therapy Aspergillus fumigatus / genetics Aspergillus fumigatus / metabolism Azoles / pharmacology Drug Resistance, Fungal / genetics Fungal Proteins / genetics Fungal Proteins / metabolism Humans Microbial Sensitivity Tests Pulmonary Aspergillosis* / drug therapy
IF 4.904
Resource
Pathogenic eukaryotic microorganisms Aspergillus fumigatus IFM 58401