title: Whole genome analysis of an MDR Beijing/W strain of Mycobacterium tuberculosis with large genomic deletions associated with resistance to isoniazid.
abstract: Mycobacterium tuberculosis (M.tb) is one of the most prevalent bacterial pathogens in the world. With geographical wide spread and hypervirulence, Beijing/W family is the most successful M.tb lineage. China is a country of high tuberculosis (TB) and high multiple drug-resistant TB (MDR-TB) burden, and the Beijing/W family strains take the largest share of MDR strains. To study the genetic basis of Beijing/W family strains' virulence and drug resistance, we performed the whole genome sequencing of M.tb strain W146, a clinical Beijing/W genotype MDR isolated from Wuxi, Jiangsu province, China. Compared with genome sequence of M.tb strain H37Rv, we found that strain W146 lacks three large fragments and the missing of furA-katG operon confers isoniazid resistance. Besides the missing of furA-katG operon, strain W146 harbored almost all known drug resistance-associated mutations. Comparison analysis of single nucleotide polymorphisms (SNPs) and indels between strain W146 and Beijing/W genotype strains and non-Beijing/W genotype strains revealed that strain W146 possessed some unique mutations, which may be related to drug resistance, transmission and pathogenicity. These findings will help to understand the large sequence polymorphisms (LSPs) and the transmission and drug resistance related genetic characteristics of the Beijing/W genotype of M.tb.
authors: Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Qiufen
authors: Q
authors: Zhang
authors: Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Baoshan
authors: B
authors: Wan
authors: Department of Laboratory Medicine, East Hospital Affiliated to Tongji University, Shanghai 200120, China.
authors: Aiping
authors: A
authors: Zhou
authors: Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Jinjing
authors: J
authors: Ni
authors: Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Zhihong
authors: Z
authors: Xu
authors: Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Shuxian
authors: S
authors: Li
authors: Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: taojing00@sjtu.edu.cn.
authors: Jing
authors: J
authors: Tao
authors: Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: yfyao@sjtu.edu.cn.
authors: YuFeng
authors: Y
authors: Yao
mesh_terms: D001483:Base Sequence; D016680:Genome, Bacterial; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D007538:Isoniazid / Q000494:pharmacology / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D010641:Phenotype; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D007538:Isoniazid
keywords: Beijing/W genotype; Genome sequencing; Isoniazid resistance; Large sequence polymorphisms; Mycobacterium tuberculosis