Prevalence of mutations conferring resistance among multi- and extensively drug-resistant Mycobacterium tuberculosis isolates in China.
To identify the mutations in multi- and extensively drug-resistant tuberculosis isolates and to evaluate the use of molecular markers of resistance, we analyzed 257 multi- and extensively drug-resistant isolates and 64 pan-sensitive isolates from 23 provinces in China. Seven loci associated with drug resistance, including rpoB for rifampin (RIF), katG, inhA and oxyR-ahpC for isoniazid (INH), gyrA and gyrB for ofloxacin (OFX), and rrs for kanmycin (KAN), were examined by DNA sequencing. Compared with the phenotypic data, the sensitivity and specificity for DNA sequencing were 91.1% and 98.4% for RIF, 80.2% and 98.4% for INH, 72.2% and 98.3% for OFX and 40% and 98.2% for KAN, respectively. The most common mutations found in RIF, INH, OFX and KAN resistance were Ser531Leu (48.2%) in rpoB, Ser315Thr (49.8%) in katG, C(-15)T (10.5%) in inhA, Asp94Gly (20.3%), Asp94Ala (12.7%) and Ala90Val (21.5%) in gyrA, and A1401G (40%) in rrs. This molecular information will be helpful to establish new molecular biology-based methods for diagnosing multi- and extensively drug-resistant tuberculosis in China.
State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.|Beijing Chest Hospital, Capital Medical University, Beijing, China.
Yan
Y
Chen
National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Bing
B
Zhao
State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Hai-can
HC
Liu
State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.|Pathogenic Biology Institute, University of South China, Hunan Province, China.
Qing
Q
Sun
State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Xiu-qin
XQ
Zhao
State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Zhi-guang
ZG
Liu
State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Kang-lin
KL
Wan
State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Li-li
LL
Zhao
D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002681:China; D004269:DNA, Bacterial / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D054908:Extensively Drug-Resistant Tuberculosis / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology*; D005798:Genes, Bacterial; D056426:Genetic Loci; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D015242:Ofloxacin / Q000494:pharmacology; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology; D017422:Sequence Analysis, DNA
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C505805:rpoB protein, Mycobacterium tuberculosis; D015242:Ofloxacin; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; D012321:DNA-Directed RNA Polymerases; D007538:Isoniazid; D012293:Rifampin