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Int J Antimicrob Agents. 2015 Feb;45(2):137-43. doi: 10.1016/j.ijantimicag.2014.09.018. Epub 2014 Nov 3.

Molecular characterisation of extensively drug-resistant Mycobacterium tuberculosis isolates in China.

Author information

1
National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, PO Box 5, Changping, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
2
National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, PO Box 5, Changping, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China; Pathogenic Biology Institute, University of South China, Hengyang 421001, Hunan Province, China.
3
Hulunbeier People's Hospital, Hulunbeier 021000, China.
4
National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
5
Zhejiang Prevention and Treatment Center of Tuberculosis, Zhejiang TCM & WM Hospital, Hangzhou 310003, China.
6
Public Central Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing 100045, China.
7
National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, PO Box 5, Changping, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China. Electronic address: wankanglin@icdc.cn.

Abstract

The emergence of extensively drug-resistant tuberculosis (XDR-TB) in China is a great threat to TB control. To determine the molecular characterisation of XDR-TB isolates from China and the correlations between specific drug resistance-associated mutations and different genotype strains, 58 XDR-TB isolates were sequenced in eight drug loci, including katG, inhA, oxyR-ahpC intergenic region, rpoB, eis, rrs, gyrA and gyrB, and were genotyped using spoligotyping and analysis of the noise transfer function region. Compared with the phenotypic data, the sensitivities and specificities for DNA sequencing were 87.9% and 100.0% for isoniazid (INH), 91.4% and 98.3% for rifampicin (RIF), 60.4% and 100.0% for kanamycin (KAN) and 81.0% and 100.0% for ofloxacin (OFX), respectively. A combination of eight drug loci predicted XDR-TB phenotypes with 53.4% sensitivity (31/58 isolates) and 100.0% specificity. The most frequent mutations among these XDR-TB isolates were katG315 and inhA-15 (for INH), 531, 526 and 516 in rpoB (for RIF), rrs1401 and eis-10 (for KAN) and 94, 90 and 91 in gyrA (for OFX). Also, among these XDR-TB isolates, 44 (75.9%) were identified as Beijing genotype strain, of which 31 (70.5%) belonged to the modern Beijing sublineage. inhA-8, rpoB526 and rpoB531 mutations demonstrated significant statistical associations with ancient and modern Beijing family sublineage (P<0.05). However, Beijing and non-Beijing genotypes showed no association with specific resistance-conferring mutations. These results will be helpful in designing new molecular biology-based techniques to diagnose XDR-TB in China.

KEYWORDS:

Extensively drug-resistant tuberculosis; Genotype; Molecular characterisation; Resistance-conferring mutations

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