Whole genome analysis of an MDR Beijing/W strain of Mycobacterium tuberculosis with large genomic deletions associated with resistance to isoniazid.
Whole genome analysis of an MDR Beijing/W strain of Mycobacterium tuberculosis with large genomic deletions associated with resistance to isoniazid.
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DOI：
10.1016/j.gene.2016.02.003
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发表时间：
2016-05
期刊：
影响因子：
3.5
通讯作者：
Qiufen Zhang;Baoshan Wan;Aiping Zhou;Jin-jing Ni;Zhihong Xu;Shuxian Li;Jing Tao;Yufeng Yao
中科院分区：
文献类型：
--
作者：
Qiufen Zhang;Baoshan Wan;Aiping Zhou;Jin-jing Ni;Zhihong Xu;Shuxian Li;Jing Tao;Yufeng Yao
结核分枝杆菌（Mycobacterium tuberculosis，M.tb）是世界上最常见的细菌性病原体之一。北京/W家族是我国最成功的结核分枝杆菌分支，具有地理分布广、毒力强等特点。我国是结核病和耐多药结核病的高发国家，耐多药结核病菌株中北京/W家族占最大比例。为了研究北京/W家族耐药菌株毒力和耐药性的遗传基础，我们对江苏省无锡市临床分离的北京/W基因型耐药结核分枝杆菌W146株进行了全基因组测序。与结核分枝杆菌H37 Rv株基因组序列比较，发现W146株缺失3个大片段，缺失的furA-katGoperon赋予异烟肼抗性。除了缺失的offurA-katGoperon外，菌株W146具有几乎所有已知的耐药相关突变。通过对W146株与北京/W基因型和非北京/W基因型的单核苷酸多态性（SNPs）和插入缺失（indels）的比较分析，发现W146株存在一些独特的突变，这些突变可能与耐药性、传播和致病性有关。本研究结果有助于了解北京/W基因型结核分枝杆菌大序列多态性（LSPs）及其传播和耐药相关的遗传特征。
Mycobacterium tuberculosis(M.tb) is one of the most prevalent bacterial pathogens in the world. With geographical wide spread and hypervirulence, Beijing/W family is the most successfulM.tblineage. China is a country of high tuberculosis (TB) and high multiple drug-resistant TB (MDR-TB) burden, and the Beijing/W family strains take the largest share of MDR strains. To study the genetic basis of Beijing/W family strains' virulence and drug resistance, we performed the whole genome sequencing ofM.tbstrain W146, a clinical Beijing/W genotype MDR isolated from Wuxi, Jiangsu province, China. Compared with genome sequence ofM.tbstrain H37Rv, we found that strain W146 lacks three large fragments and the missing offurA-katGoperon confers isoniazid resistance. Besides the missing offurA-katGoperon, strain W146 harbored almost all known drug resistance-associated mutations. Comparison analysis of single nucleotide polymorphisms (SNPs) and indels between strain W146 and Beijing/W genotype strains and non-Beijing/W genotype strains revealed that strain W146 possessed some unique mutations, which may be related to drug resistance, transmission and pathogenicity. These findings will help to understand the large sequence polymorphisms (LSPs) and the transmission and drug resistance related genetic characteristics of the Beijing/W genotype ofM.tb.