Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance

被引：269

作者：

Zhang, Hongtai ^{[1
,2
]}

Li, Dongfang ^{[3
,4
]}

Zhao, Lili ^{[5
,6
]}

Fleming, Joy ^{[1
]}

Lin, Nan ^{[7
]}

Wang, Ting ^{[1
]}

Liu, Zhangyi ^{[3
]}

Li, Chuanyou ^{[8
]}

Galwey, Nicholas ^{[1
]}

Deng, Jiaoyu ^{[9
]}

Zhou, Ying ^{[1
]}

Zhu, Yuanfang ^{[3
]}

Gao, Yunrong ^{[1
]}

Wang, Tong ^{[3
]}

Wang, Shihua ^{[7
]}

Huang, Yufen ^{[3
]}

Wang, Ming ^{[1
]}

Zhong, Qiu ^{[10
]}

Zhou, Lin ^{[10
]}

Chen, Tao ^{[10
]}

Zhou, Jie ^{[11
]}

Yang, Ruifu ^{[3
]}

Zhu, Guofeng ^{[12
]}

Hang, Haiying ^{[1
]}

Zhang, Jia ^{[1
]}

Li, Fabin ^{[13
]}

Wan, Kanglin ^{[5
,6
]}

Wang, Jun ^{[3
]}

Zhang, Xian-En ^{[2
,9
]}

Bi, Lijun ^{[1
]}

机构：

[1] Chinese Acad Sci, Inst Biophys, Key Lab Noncoding RNA, Beijing 100080, Peoples R China

[2] Chinese Acad Sci, Inst Biophys, State Key Lab Biomacromol, Beijing 100080, Peoples R China

[3] BGI Shenzhen, Shenzhen, Peoples R China

[4] Shenzhen Key Lab Unknown Pathogen Identificat, Shenzhen, Peoples R China

[5] Chinese Ctr Dis Control & Prevent, Natl Inst Communicable Dis Control & Prevent, Beijing, Peoples R China

[6] State Key Lab Infect Dis Prevent & Control, Beijing, Peoples R China

[7] Fujian Agr & Forestry Univ, Coll Life Sci, Fuzhou, Peoples R China

[8] Capital Med Univ, Beijing Chest Hosp, Beijing, Peoples R China

[9] Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Peoples R China

[10] Ctr TB Control Guangdong Prov, Guangzhou, Guangdong, Peoples R China

[11] Fourth Peoples Hosp, Foshan, Peoples R China

[12] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China

[13] Heilongjiang Ctr TB Control & Prevent, Harbin, Peoples R China

来源：

NATURE GENETICS | 2013年 / 45卷 / 10期

基金：

中国国家自然科学基金;

关键词：

LONG-TERM EXPERIMENT; ISONIAZID RESISTANCE; MULTIDRUG-RESISTANT; MUTATION-RATE; EVOLUTION; BIOSYNTHESIS; MECHANISMS; DIVERSITY; VIRULENCE; TARGET;

D O I：

10.1038/ng.2735

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The worldwide emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis threatens to make this disease incurable(1,2). Drug resistance mechanisms are only partially understood(3-5), 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(6-8), 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.

引用

页码：1255 / U217

页数：8

共 58 条

[1]

[Anonymous], 2011, Global Tuberculosis Control 2011

[2]

[Anonymous], 2009, TREATM TUB GUID NAT, V4th edn

[3]

[Anonymous], 2009, GUID SURV DRUG RES T, V4

[4]

[Anonymous], POL GUID TB DRUG SUS

[5] Sequence-Based Analysis Uncovers an Abundance of Non-Coding RNA in the Total Transcriptome of Mycobacterium tuberculosis [J].

Arnvig, Kristine B. ;

Comas, Inaki ;

Thomson, Nicholas R. ;

Houghton, Joanna ;

Boshoff, Helena I. ;

Croucher, Nicholas J. ;

Rose, Graham ;

Perkins, Timothy T. ;

Parkhill, Julian ;

Dougan, Gordon ;

Young, Douglas B. .

PLOS PATHOGENS, 2011, 7 (11)

[6] Genome evolution and adaptation in a long-term experiment with Escherichia coli [J].

Barrick, Jeffrey E. ;

Yu, Dong Su ;

Yoon, Sung Ho ;

Jeong, Haeyoung ;

Oh, Tae Kwang ;

Schneider, Dominique ;

Lenski, Richard E. ;

Kim, Jihyun F. .

NATURE, 2009, 461 (7268) :1243-U74

[7] Tandem repeats finder: a program to analyze DNA sequences [J].

Benson, G .

NUCLEIC ACIDS RESEARCH, 1999, 27 (02) :573-580

[8] Biosynthesis of mycobacterial arabinogalactan:: identification of a novel α(1→3) arabinofuranosyltransferase [J].

Birch, Helen L. ;

Alderwick, Luke J. ;

Bhatt, Apoorva ;

Rittmann, Doris ;

Krumbach, Karin ;

Singh, Albel ;

Bai, Yu ;

Lowary, Todd L. ;

Eggeling, Lothar ;

Besra, Gurdyal S. .

MOLECULAR MICROBIOLOGY, 2008, 69 (05) :1191-1206

[9] Microevolution of extensively drug-resistant tuberculosis in Russia [J].

Casali, Nicola ;

Nikolayevskyy, Vladyslav ;

Balabanova, Yanina ;

Ignatyeva, Olga ;

Kontsevaya, Irina ;

Harris, Simon R. ;

Bentley, Stephen D. ;

Parkhill, Julian ;

Nejentsev, Sergey ;

Hoffner, Sven E. ;

Horstmann, Rolf D. ;

Brown, Timothy ;

Drobniewski, Francis .

GENOME RESEARCH, 2012, 22 (04) :735-745

[10] Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence [J].

Cole, ST ;

Brosch, R ;

Parkhill, J ;

Garnier, T ;

Churcher, C ;

Harris, D ;

Gordon, SV ;

Eiglmeier, K ;

Gas, S ;

Barry, CE ;

Tekaia, F ;

Badcock, K ;

Basham, D ;

Brown, D ;

Chillingworth, T ;

Connor, R ;

Davies, R ;

Devlin, K ;

Feltwell, T ;

Gentles, S ;

Hamlin, N ;

Holroyd, S ;

Hornby, T ;

Jagels, K ;

Krogh, A ;

McLean, J ;

Moule, S ;

Murphy, L ;

Oliver, K ;

Osborne, J ;

Quail, MA ;

Rajandream, MA ;

Rogers, J ;

Rutter, S ;

Seeger, K ;

Skelton, J ;

Squares, R ;

Squares, S ;

Sulston, JE ;

Taylor, K ;

Whitehead, S ;

Barrell, BG .

NATURE, 1998, 393 (6685) :537-+

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