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Chinese Journal of Antituberculosis ›› 2022, Vol. 44 ›› Issue (11): 1126-1134.doi: 10.19982/j.issn.1000-6621.20220224

• Original Articles • Previous Articles     Next Articles

Analysis on characteristic of drug resistance-associated gene mutations and the correlation with genotypes among Mycobacterium tuberculosis isolates in Zhejiang Province

Wu Kunyang1, Lu Yewei2, Zhang Mingwu1, Zhu Yelei1, Li Xiangchen2, Pan Junhang1, Wang Xiaomeng1, Wang Wei3, Jiang Minmin4, Peng Xiaojun2, Wang Weixin2, Gao Junshun2, Liu Zhengwei1()   

  1. 1Laboratory for Department of TB Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China
    2Department of Bioinformatics, Cosmos Wisdom Biotech Co., Ltd., Hangzhou 311215, China
    3Department of Clinical Laboratory, the First Hospital of Jiaxing, Jiaxing 314001, China
    4Department of Clinical Laboratory, the First People’s Hospital of Jiashan, Jiaxing 314199, China
  • Received:2022-06-08 Online:2022-11-10 Published:2022-11-03
  • Contact: Liu Zhengwei E-mail:zhwliu@cdc.zj.cn
  • Supported by:
    Zhejiang Provincial Medical and Health Science and Technology Plan Project(2020keyan512)

Abstract:

Objective: To evaluate the drug resistance analysis and detection performance of whole-genome sequencing (WGS) on the characteristic of drug resistance-associated gene mutations and its correlation with genotypes among Mycobacterium tuberculosis (MTB) isolates in Zhejiang Province. Methods: WGS analysis of 14 drugs was performed on 808 MTB strains collected from the fifth tuberculosis drug resistance surveillance project in Zhejiang Province from 2018 and 2019. MTB genotypes and drug resistance-related gene mutations were identified, meanwhile, their relationship and the consistency of WGS drug susceptibility test results and phenotypic drug susceptibility test results of isoniazid were analyzed. Results: Of the 808 MTB strains, 153 were identified with drug-resistant gene mutations related to 11 anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol, pyrazinamide, streptomycin, fluoroquinolones, amikacin, kanamycin, capreomycin, ethionamide, para-aminosalicylic acid) and the overall mutation rate was 18.9%. The major drug resistance-associated gene mutation types were katG-315-S/T (isoniazid, 60.0% (45/75)), rpoB-450-S/L (rifampicin, 57.1% (16/28)), embB-306-M/V (ethambutol, 43.8% (7/16)), rpsL-43-K/R (streptomycin, 65.5% (36/55)), gyrA-94-D/G (fluoroquinolones, 36.6% (15/41)), rrs-1402-C/A (amikacin, 3/3), rrs-1402-C/A (kanamycin, 3/4), rrs-1402-C/A (capreomycin, 3/3), inhA-15-C/T (ethionamide, 65.0% (13/20)) and thyA-75-H/N (para-aminosalicylic acid, 7/8). Drug resistance-associated mutations on rpsL gene were detected only in Beijing genotype strains (6.8% (40/586) vs. 0.0% (0/222), χ2=15.943, P=0.000). The mutation rate of katG-315 was higher in Beijing genotype strains (6.8% (40/586)) than non-Beijing genotype strains (3.2% (7/222)) and the difference was statistically significant (χ2=3.964, P=0.046). The sensitivity, specificity, positive predictive value, negative predictive value, consistency rate and Kappa value of the WGS drug resistance profiling method for isoniazid were 87.5% (49/56), 98.0% (680/694), 77.8% (49/63), 99.0% (680/687), 97.2% (729/750) and 0.808, respectively. Conclusion: The major drug resistance-associated gene mutations of 11 drugs were on katG, rpoB, embB, pncA, rpsL, gyrA, rrs, thyA and inhA among Zhejiang Province MTB strains. Mutations on rpsL, katG-315 and rpsL-43 were related with Beijing genotypes. The WGS drug resistance profiling method has comprehensive detection performance for isoniazid, but the performance of some drug-resistant gene mutations is poor.

Key words: Mycobacterium tuberculosis, Drug resistance,bacterial, Sequence analysis,DNA, Mutation, Genotype

CLC Number: