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 we...

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Autores principales: Khateb, Aiah, Gago, Sara, Bromley, Michael, Richardson, Malcom, Bowyer, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Mechanisms of Resistance
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10112202/
https://www.ncbi.nlm.nih.gov/pubmed/36975834
http://dx.doi.org/10.1128/aac.01253-22
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author Khateb, Aiah
Gago, Sara
Bromley, Michael
Richardson, Malcom
Bowyer, Paul
author_facet Khateb, Aiah
Gago, Sara
Bromley, Michael
Richardson, Malcom
Bowyer, Paul
author_sort Khateb, Aiah
collection PubMed
description 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.
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spelling pubmed-101122022023-04-19 Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus Khateb, Aiah Gago, Sara Bromley, Michael Richardson, Malcom Bowyer, Paul Antimicrob Agents Chemother Mechanisms of Resistance 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. American Society for Microbiology 2023-03-28 /pmc/articles/PMC10112202/ /pubmed/36975834 http://dx.doi.org/10.1128/aac.01253-22 Text en Copyright © 2023 Khateb et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Mechanisms of Resistance
Khateb, Aiah
Gago, Sara
Bromley, Michael
Richardson, Malcom
Bowyer, Paul
Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus
title Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus
title_full Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus
title_fullStr Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus
title_full_unstemmed Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus
title_short Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus
title_sort aneuploidy is associated with azole resistance in aspergillus fumigatus
topic Mechanisms of Resistance
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10112202/
https://www.ncbi.nlm.nih.gov/pubmed/36975834
http://dx.doi.org/10.1128/aac.01253-22
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