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从乌克兰临床分离株中鉴定耐药相关结核分枝杆菌基因的下一代测序。

Next-Generation Sequencing for Characterizing Drug Resistance-Conferring Mycobacterium tuberculosis Genes from Clinical Isolates in the Ukraine.

机构信息

Longhorn Vaccines and Diagnostics, San Antonio, Texas, USA

Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine.

出版信息

J Clin Microbiol. 2018 May 25;56(6). doi: 10.1128/JCM.00009-18. Print 2018 Jun.

DOI:10.1128/JCM.00009-18
PMID:29563202
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5971536/
Abstract

The Ukraine ranks among the top 20 countries with the highest number of multidrug-resistant (MDR) and extensively drug resistant (XDR) cases in the world. However, little is known of the genetic diversity, i.e., resistance signatures, in clinical isolates from this region. We analyzed seven of most prevalent MDR/XDR antibiotic resistance-conferring genes from clinical isolates ( = 75) collected from geographically diverse Ukrainian oblasts and the southern Crimean peninsula. Genomic analysis revealed that 6 (8%) were sensitive, 3 (4%) were resistant to at least one antibiotic but were not MDR, 40 (53%) were MDR, and 26 (35%) were XDR. The majority of isolates (81%) were of the Beijing-like lineage. This is the first study to use next-generation sequencing (NGS) of clinical isolates from the Ukraine to characterize mutations in genes conferring drug resistance. Several isolates harbored drug resistance signatures that have not been observed in other countries with high-burden tuberculosis. Most notably, the absence of gene promoter mutations, a diversity of mutation types in the resistance-determining region, and detection of heteroresistance provide a broader understanding of MDR/XDR from this area of the world.

摘要

乌克兰是世界上拥有最多耐多药(MDR)和广泛耐药(XDR)病例的前 20 个国家之一。然而,人们对该地区临床分离株的遗传多样性(即耐药特征)知之甚少。我们分析了从乌克兰各地理区域和克里米亚半岛南部采集的 75 株临床分离株中最常见的七种耐多药/广泛耐药抗生素耐药基因。基因组分析显示,6 株(8%)对所有抗生素均敏感,3 株(4%)至少对一种抗生素耐药但非 MDR,40 株(53%)为 MDR,26 株(35%)为 XDR。大多数分离株(81%)属于北京样谱系。这是首次使用下一代测序(NGS)对来自乌克兰的临床分离株进行研究,以鉴定耐药基因的突变。一些分离株具有在其他结核病负担高的国家未观察到的耐药特征。值得注意的是,缺失 基因启动子突变、耐药决定区中多样化的突变类型以及异质性耐药的检测,为我们提供了对该地区 MDR/XDR 的更广泛认识。

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