| Literature DB >> 23995137 |
Hongtai Zhang1, Dongfang Li, Lili Zhao, Joy Fleming, Nan Lin, Ting Wang, Zhangyi Liu, Chuanyou Li, Nicholas Galwey, Jiaoyu Deng, Ying Zhou, Yuanfang Zhu, Yunrong Gao, Tong Wang, Shihua Wang, Yufen Huang, Ming Wang, Qiu Zhong, Lin Zhou, Tao Chen, Jie Zhou, Ruifu Yang, Guofeng Zhu, Haiying Hang, Jia Zhang, Fabin Li, Kanglin Wan, Jun Wang, Xian-En Zhang, Lijun Bi.
Abstract
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.Entities:
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Year: 2013 PMID： 23995137 DOI： 10.1038/ng.2735
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330