A genome-wide analysis of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis Beijing genotype
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  • 作者：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)
  • 关键词：Mycobacterium tuberculosis ; Resistance ; Beijing genotype ; Genome ; DNA repair
  • 刊名：Molecular Genetics and Genomics
  • 出版年：2013
  • 出版时间：September 2013
  • 年：2013
  • 卷：288
  • 期：9
  • 页码：425-436
  • 全文大小：453KB
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  • 作者单位：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. College of Life Sciences, Fudan University, Shanghai, 200433, People鈥檚 Republic of China
    2. Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, People鈥檚 Republic of China
    3. Department of Medical Microbiology and Parasitology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People鈥檚 Republic of China
    4. Wuxi Hospital of Infection Disease, Wuxi, 214005, Jiangsu, People鈥檚 Republic of China
    5. Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Medical School, Tongji University, Shanghai, 200433, People鈥檚 Republic of China
  • ISSN：1617-4623
文摘
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.

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