Aneuploidy is associated with azole resistance in Aspergillus fumigatus

Aiah Khateb; Sara Gago; Michael Bromley; Malcolm Richardson; Paul Bowyer

Aneuploidy is associated with azole resistance in Aspergillus fumigatus

Aiah Khateb, Sara Gago, Michael Bromley, Malcolm Richardson, Paul Bowyer

Research output: Contribution to journal › Article › peer-review

Abstract

Azole resistance in Aspergillus fumigatus is on the rise. Non-target 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. 7/16 CPA isolates showed genomic duplications compared to 0/18 invasive isolates. Duplication of regions including cyp51A increased gene expression. Our results suggest aneuploidy as an azole resistance mechanism in CPA.

Original language	English
Journal	Antimicrobial Agents and Chemotherapy
Publication status	Accepted/In press - 9 Feb 2023

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Bowyer_Aneuploidy-amended-v3
Accepted author manuscript, 599 KB
Embargo ends: 1/01/33

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title = "Aneuploidy is associated with azole resistance in Aspergillus fumigatus",

abstract = "Azole resistance in Aspergillus fumigatus is on the rise. Non-target 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. 7/16 CPA isolates showed genomic duplications compared to 0/18 invasive isolates. Duplication of regions including cyp51A increased gene expression. Our results suggest aneuploidy as an azole resistance mechanism in CPA.",

author = "Aiah Khateb and Sara Gago and Michael Bromley and Malcolm Richardson and Paul Bowyer",

year = "2023",

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journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

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T1 - Aneuploidy is associated with azole resistance in Aspergillus fumigatus

AU - Khateb, Aiah

AU - Gago, Sara

AU - Bromley, Michael

AU - Richardson, Malcolm

AU - Bowyer, Paul

PY - 2023/2/9

Y1 - 2023/2/9

N2 - Azole resistance in Aspergillus fumigatus is on the rise. Non-target 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. 7/16 CPA isolates showed genomic duplications compared to 0/18 invasive isolates. Duplication of regions including cyp51A increased gene expression. Our results suggest aneuploidy as an azole resistance mechanism in CPA.

AB - Azole resistance in Aspergillus fumigatus is on the rise. Non-target 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. 7/16 CPA isolates showed genomic duplications compared to 0/18 invasive isolates. Duplication of regions including cyp51A increased gene expression. Our results suggest aneuploidy as an azole resistance mechanism in CPA.

M3 - Article

SN - 0066-4804

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

ER -

Aneuploidy is associated with azole resistance in Aspergillus fumigatus

Abstract

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