Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance
Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance
复制标题
对来自中国的 161 株结核分枝杆菌分离株进行基因组测序，鉴定出与耐药性相关的基因和基因间区域
DOI：
10.1038/ng.2735
复制
发表时间：
2013-10-01
期刊：
影响因子：
30.8
通讯作者：
Bi, Lijun
中科院分区：
文献类型：
--
作者：
Zhang, Hongtai;Li, Dongfang;Bi, Lijun
世界范围内出现的多药耐药（MDR）和广泛耐药（XDR）结核病有可能使这种疾病无法治愈。目前对耐药机制的认识还不完全清楚，对M。结核病是否足够全面仍不清楚。我们对161株耐药菌株进行了测序和分析，发现72个新基因，28个基因间区域（IGRs），11个非同义SNPs和10个IGR SNPs与耐药有着强而一致的关联。基于我们对分离株中非同义SNP与同义SNP的dN/dS比值的研究，我们认为，此处鉴定的耐药相关基因可能包含这些分离株中由于药物压力而产生的所有非同义SNP，因此应代表这些分离株和抗生素的一组接近完整的耐药相关基因。我们的工作表明，耐药的遗传基础比以前预期的更为复杂，并为阐明未知的耐药机制提供了坚实的基础。
The worldwide emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis threatens to make this disease incurable. Drug resistance mechanisms are only partially understood, and whether the current understanding of the genetic basis of drug resistance in M. tuberculosis is sufficiently comprehensive remains unclear. Here we sequenced and analyzed 161 isolates with a range of drug resistance profiles, discovering 72 new genes, 28 intergenic regions (IGRs), 11 nonsynonymous SNPs and 10 IGR SNPs with strong, consistent associations with drug resistance. On the basis of our examination of the dN/dS ratios of nonsynonymous to synonymous SNPs among the isolates, we suggest that the drug resistance-associated genes identified here likely contain essentially all the nonsynonymous SNPs that have arisen as a result of drug pressure in these isolates and should thus represent a near-complete set of drug resistance-associated genes for these isolates and antibiotics. Our work indicates that the genetic basis of drug resistance is more complex than previously anticipated and provides a strong foundation for elucidating unknown drug resistance mechanisms.