Beijing genotype of Mycobacterium tuberculosis is significantly associated with linezolid resistance in multidrug-resistant and extensively drug-resistant tuberculosis in China.
Linezolid (LNZ) is a promising antimicrobial agent for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). To investigate the efficacy of LNZ among MDR-TB and XDR-TB in China, the LNZ susceptibility of 158 MDR-TB isolates from the national drug resistance survey was determined by the minimum inhibitory concentration method. The 158 MDR-TB isolates were also sequenced in the 23S rRNA, rplC and rplD genes conferring LNZ resistance and were typed using spoligotyping to identify the Beijing genotype of Mycobacterium tuberculosis. Overall, the prevalence of LNZ-resistant isolates was 10.8% (17/158) among MDR-TB isolates circulating in China. Beijing genotype was significantly associated with LNZ resistance in MDR-TB and XDR-TB (odds ratio=4.66, 95% confidence interval 1.03-21.16; P=0.033). In addition, a higher frequency of LNZ-resistant isolates was observed among XDR-TB strains (60%) compared with the MDR (5.6%; P<0.001) and pre-XDR groups (12.2%; P=0.004). Mutations in 23S rRNA and rplC were responsible for only 29.4% of LNZ-resistant M. tuberculosis among MDR-TB isolates, and a novel non-synonymous substitution His155Asp in rplC was first identified to be contributing to low-level LNZ resistance (2μg/mL) in M. tuberculosis. The unsatisfactory correlation between mutant genotypes highlights the urgent need to investigate another mechanism for LNZ resistance that has not yet been described.
Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, 28# Fuxing Road, Haidian District, Beijing 100853, China.
Zhijian
Z
Zhang
Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, 28# Fuxing Road, Haidian District, Beijing 100853, China; National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155 Chang Bai Road, Changping District, Beijing 102206, China. Electronic address: pangyu@chinatb.org.
Yu
Y
Pang
National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155 Chang Bai Road, Changping District, Beijing 102206, China.
Yufeng
Y
Wang
Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, 28# Fuxing Road, Haidian District, Beijing 100853, China. Electronic address: liuchangting301@163.com.
Changting
C
Liu
National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155 Chang Bai Road, Changping District, Beijing 102206, China. Electronic address: zhaoyanlin@chinatb.org.
Yanlin
Y
Zhao
D000081:Acetamides / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology*; D002681:China / Q000453:epidemiology; D024901:Drug Resistance, Multiple, Bacterial; D005838:Genotype; D006801:Humans; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D017720:Molecular Epidemiology; D058889:Molecular Typing; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000187:drug effects* / Q000302:isolation & purification; D023303:Oxazolidinones / Q000494:pharmacology*; D015995:Prevalence; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D017422:Sequence Analysis, DNA; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology / Q000382:microbiology*
D000081:Acetamides; D000995:Antitubercular Agents; D023303:Oxazolidinones; D012338:RNA, Ribosomal, 23S; D000069349:Linezolid
Linezolid; Multidrug resistance; Tuberculosis