A genome-wide analysis of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis Beijing genotype
A genome-wide analysis of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis Beijing genotype
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结核分枝杆菌北京基因型多重耐药和广泛耐药菌株的全基因组分析
DOI：
10.1007/s00438-013-0758-4
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发表时间：
2013-09-01
影响因子：
3.1
通讯作者：
Li, Yao
中科院分区：
文献类型：
--
作者：
Wu, Wei;Zheng, Huajun;Li, Yao
结核分枝杆菌（MTB）北京基因型是世界上传播最成功的MTB谱系之一。在我国，耐多药结核病发病率明显高于全球平均水平，其中北京基因型菌株所占耐多药菌株比例最大。为了研究北京基因型通常与结核病暴发和耐药性相关的流行病学发现的遗传基础，我们利用全基因组测序确定了四种临床分离株的基因组序列：两种广泛耐药菌株（XDR1219、XDR1221）和两种多重耐药菌株（WX1、WX3）。鉴定出四种北京毒株的大量单独和共有的 SNP。我们的分离株几乎包含所有经典的耐药相关突变。两种XDR菌株中导致耐药的突变与临床定量耐药水平一致。 COG分析显示，北京菌株的细胞壁/膜/包膜生物发生（COG M）、次生代谢物生物合成、转运和分解代谢（COG Q）、脂质转运和代谢（COG I）和防御机制（COG V）的突变丰度显着较高。研究的四个北京毒株的共有突变基因在三个 DNA 修复途径中显着过高。我们的分析促进了对北京株基因组多态性的认识，并为其广泛传播能力和耐药性提供了分子遗传学基础。
The Beijing genotype of Mycobacterium tuberculosis (MTB) is one of the most successful MTB lineages that has disseminated in the world. In China, the rate of multidrug-resistant (MDR) tuberculosis is significantly higher than the global average rate, and the Beijing genotype strains take the largest share of MDR strains. To study the genetic basis of the epidemiological findings that Beijing genotype has often been associated with tuberculosis outbreaks and drug resistance, we determined the genome sequences of four clinical isolates: two extensively drug resistant (XDR1219, XDR1221) and two multidrug resistant (WX1, WX3), using whole-genome sequencing. A large number of individual and shared SNPs of the four Beijing strains were identified. Our isolates harbored almost all classic drug resistance-associated mutations. The mutations responsible for drug resistance in the two XDR strains were consistent with the clinical quantitative drug resistance levels. COG analysis revealed that Beijing strains have significantly higher abundances of the mutations responsible for cell wall/membrane/envelope biogenesis (COG M), secondary metabolites biosynthesis, transport and catabolism (COG Q), lipid transport and metabolism (COG I) and defense mechanisms (COG V). The shared mutated genes of the four studied Beijing strains were significantly overrepresented in three DNA repair pathways. Our analyses promote the understanding of the genome polymorphism of the Beijing family strains and provide the molecular genetic basis for their wide dissemination capacity and drug resistance.