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Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus. 2023

Aiah Khateb, and Sara Gago, and Michael Bromley, and Malcom Richardson, and Paul Bowyer
Manchester Fungal Infection Group, Division of Evolution Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Core Technology Facility, Manchester, United Kingdom.

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.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D005656 Fungal Proteins Proteins found in any species of fungus. Fungal Gene Products,Fungal Gene Proteins,Fungal Peptides,Gene Products, Fungal,Yeast Proteins,Gene Proteins, Fungal,Peptides, Fungal,Proteins, Fungal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000782 Aneuploidy The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1). Aneuploid,Aneuploid Cell,Aneuploid Cells,Aneuploidies,Aneuploids,Cell, Aneuploid,Cells, Aneuploid
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics
D001228 Aspergillosis Infections with fungi of the genus ASPERGILLUS. Aspergillus Infection,Aspergilloses,Aspergillus Infections,Infection, Aspergillus,Infections, Aspergillus
D001232 Aspergillus fumigatus A species of imperfect fungi from which the antibiotic fumigatin is obtained. Its spores may cause respiratory infection in birds and mammals. Aspergillus fumigates,Neosartorya fumigata,Sartorya fumigata
D001393 Azoles Five membered rings containing a NITROGEN atom. Azole
D055732 Pulmonary Aspergillosis Infections of the respiratory tract with fungi of the genus ASPERGILLUS. Bronchopulmonary Aspergillosis,Aspergilloses, Bronchopulmonary,Aspergillosis, Bronchopulmonary,Bronchopulmonary Aspergilloses,Lung Aspergillosis,Aspergillose, Bronchopulmonary,Aspergilloses, Lung,Aspergillosis, Lung,Aspergillosis, Pulmonary,Bronchopulmonary Aspergillose,Pulmonary Aspergilloses
D025141 Drug Resistance, Fungal The ability of fungi to resist or to become tolerant to chemotherapeutic agents, antifungal agents, or antibiotics. This resistance may be acquired through gene mutation. Antibiotic Resistance, Fungal,Antifungal Drug Resistance,Resistance, Antifungal Drug

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