Molecular Genetics and Genomics

, Volume 288, Issue 9, pp 425–436 | Cite as

A genome-wide analysis of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis Beijing genotype

  • Wei Wu
  • Huajun Zheng
  • Lu Zhang
  • Zilu Wen
  • Shulin Zhang
  • Hao Pei
  • Guohua Yu
  • Yongqiang Zhu
  • Zhenling Cui
  • Zhongyi Hu
  • Honghai Wang
  • Yao Li
Original Paper

Abstract

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.

Keywords

Mycobacterium tuberculosis Resistance Beijing genotype Genome DNA repair 

Abbreviations

MTB

Mycobacterium tuberculosis

MDR

Multidrug resistant

COG

Clusters of Orthologous Groups of proteins

TB

Tuberculosis

RIF

Rifampicin

INH

Isoniazid

MDR-TB

Multidrug-resistant tuberculosis

XDR-TB

Extensively drug-resistant tuberculosis

FQs

Fluoroquinolones

SNPs

Single nucleotide polymorphisms

MIC

Minimum inhibitory concentration

ORFs

Open reading frames

TBDB

TB Drug Resistance Mutation Database

STR

Streptomycin

EMB

Ethambutol

OFX

Ofloxacin

QRDR

Quinolone resistance-determining region

KAN

Kanamycin

AMI

Amikacin

CAP

Capreomycin

MMR

Mismatch repair

BER

Base excision repair

NER

Nucleotide excision repair

NHEJ

Non-homologous end joining

WGS

Whole-genome sequence

DIM

Phthiocerol dimycocerosates

PGL

Phenolglycolipids

ROS

Reactive oxygen species

RNI

Reactive nitrogen intermediates

Supplementary material

438_2013_758_MOESM1_ESM.xlsx (350 kb)
Supplementary material 1 (XLSX 349 kb)
438_2013_758_MOESM2_ESM.xlsx (102 kb)
Supplementary material 2 (XLSX 101 kb)
438_2013_758_MOESM3_ESM.xlsx (17 kb)
Supplementary material 3 (XLSX 17 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Wei Wu
    • 1
  • Huajun Zheng
    • 2
  • Lu Zhang
    • 1
  • Zilu Wen
    • 3
  • Shulin Zhang
    • 3
  • Hao Pei
    • 4
  • Guohua Yu
    • 1
  • Yongqiang Zhu
    • 2
  • Zhenling Cui
    • 5
  • Zhongyi Hu
    • 5
  • Honghai Wang
    • 1
  • Yao Li
    • 1
  1. 1.College of Life SciencesFudan UniversityShanghaiPeople’s Republic of China
  2. 2.Shanghai-MOST Key Laboratory of Health and Disease GenomicsChinese National Human Genome Center at ShanghaiShanghaiPeople’s Republic of China
  3. 3.Department of Medical Microbiology and ParasitologyShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
  4. 4.Wuxi Hospital of Infection DiseaseWuxiPeople’s Republic of China
  5. 5.Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Medical SchoolTongji UniversityShanghaiPeople’s Republic of China

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