title: Genotyping and molecular characteristics of multidrug-resistant Mycobacterium tuberculosis isolates from China.
abstract: OBJECTIVE
  The aim of this study was to explore the population structure of multidrug-resistant (MDR) tuberculosis strains and distribution of resistance-associated nucleotide alteration among the different genotype MDR strains in China.
  
  
  METHODS
  The genotypes of 376 MDR strain were analyzed by 15-loci MIRU-VNTR and RD105 deletion-targeted multiplex PCR (DTM-PCR) method. In addition, all the MDR isolates were sequenced for genetic mutations conferring rifampicin (rpoB) and isonizid resistance (katG, inhA and oxyR-ahpC).
  
  
  RESULTS
  Among the 376 MDR isolates, 261 (69.4%) belonged to Beijing genotype, including 177 modern Beijing strains (67.8%) and 84 ancient Beijing (32.2%) strains. The percentages of streptomycin-resistant, kanamycin-resistant, pre-XDR and XDR TB in modern Beijing genotype were significantly lower than ancient genotype (P < 0.05). The Beijing MDR strains had significantly higher proportions of ofloxacin-resistant and pre-XDR isolates than non-Beijing strains (P < 0.01). In addition, the clustering rate of modern Beijing strains was significantly higher than that of ancient Beijing strains (46.3% vs. 11.9%, P < 0.01). 94.7% and 79.3% of MDR isolates harbored genetic mutations conferring rifampicin and isonizid resistance, respectively, and the most prevalent mutation was located in codon rpoB531 and katG315. In addition, the rpoB531 and katG mutation were more frequently observed among Beijing genotype strains than non-Beijing strains, while non-Beijing genotype showed stronger association with isolates lacking mutation in rifampicin resistance determination region (P < 0.05).
  
  
  CONCLUSIONS
  Our findings demonstrated that ancient Beijing MDR strains were associated with drug resistance, while modern Beijing MDR strains were more likely to be clustered.
authors.affiliation: Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, China; National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Liaoning Provincial Center for Disease Control and Prevention, Shenyang, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Geping
authors.initials: G
authors.lastname: Qu
authors.affiliation: Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Jichun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, China; National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address: pangyu@chinatb.org.
authors.forename: Yu
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, China. Electronic address: liuchangting301@163.com.
authors.forename: Changting
authors.initials: C
authors.lastname: Liu
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address: zhaoyanlin@chinatb.org.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002374:Catalase / Q000235:genetics; D002681:China; D012321:DNA-Directed RNA Polymerases; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D007538:Isoniazid / Q000494:pharmacology; D017720:Molecular Epidemiology; D058889:Molecular Typing; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification*; D010088:Oxidoreductases / Q000235:genetics; D010802:Phylogeny; D012293:Rifampin / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; D012321:DNA-Directed RNA Polymerases; D007538:Isoniazid; D012293:Rifampin
keywords: Genotyping; Multidrug-resistant; Mycobacterium tuberculosis