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非整倍体与烟曲霉中唑类药物耐药性有关。

Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus.

机构信息

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.

Department of Medical Laboratory Technology, Collage of Applied Medical Science, Taibah University, Medina, Saudi Arabia.

出版信息

Antimicrob Agents Chemother. 2023 Apr 18;67(4):e0125322. doi: 10.1128/aac.01253-22. Epub 2023 Mar 28.

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 51A, increased gene expression. Our results suggest aneuploidy as an azole resistance mechanism in CPA.

摘要

烟曲霉中的唑类耐药性正在上升。非靶介导机制是慢性肺部曲霉病(CPA)中唑类耐药的常见原因。在这里,我们使用全基因组测序来研究耐药机制。对 16 株来自 CPA 的唑类耐药烟曲霉分离株进行测序,以评估基因组重排。与 18 株侵袭性分离株相比,16 株 CPA 分离株中有 7 株显示基因组重复,而没有分离株显示。包括 51A 在内的区域的重复增加了基因表达。我们的研究结果表明,非整倍体是 CPA 中唑类耐药的一种机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/846c/10112202/decb3800949d/aac.01253-22-f001.jpg

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