title: Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance.
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.
authors.affiliation: 1] Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. [2] State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. [3].
authors.forename: Hongtai
authors.initials: H
authors.lastname: Zhang
authors.forename: Dongfang
authors.initials: D
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.forename: Joy
authors.initials: J
authors.lastname: Fleming
authors.forename: Nan
authors.initials: N
authors.lastname: Lin
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Zhangyi
authors.initials: Z
authors.lastname: Liu
authors.forename: Chuanyou
authors.initials: C
authors.lastname: Li
authors.forename: Nicholas
authors.initials: N
authors.lastname: Galwey
authors.forename: Jiaoyu
authors.initials: J
authors.lastname: Deng
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yunrong
authors.initials: Y
authors.lastname: Gao
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Shihua
authors.initials: S
authors.lastname: Wang
authors.forename: Yufen
authors.initials: Y
authors.lastname: Huang
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zhong
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Ruifu
authors.initials: R
authors.lastname: Yang
authors.forename: Guofeng
authors.initials: G
authors.lastname: Zhu
authors.forename: Haiying
authors.initials: H
authors.lastname: Hang
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.forename: Fabin
authors.initials: F
authors.lastname: Li
authors.forename: Kanglin
authors.initials: K
authors.lastname: Wan
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Xian-En
authors.initials: XE
authors.lastname: Zhang
authors.forename: Lijun
authors.initials: L
authors.lastname: Bi
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D002681:China; D004352:Drug Resistance, Microbial / Q000235:genetics*; D016680:Genome, Bacterial; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D020641:Polymorphism, Single Nucleotide
chemical_list: D000995:Antitubercular Agents