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Chinese Journal of Antituberculosis ›› 2012, Vol. 34 ›› Issue (6): 354-359.

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Correlation between levels of isoniazid and rifampicin resistance and targeted gene mutations in Mycobacterium tuberculosis

LI Gui-lian, ZHANG Jing-rui, ZHAO Xiu-qin,YANG Ao, LIAN Lu-lu, WAN Kang-lin   

  1. Department of tuberculosis Control of National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, State Key Laboratory for Infectious Disease Prevention and Control, Beijing 102206, China
  • Received:2012-01-11 Online:2012-06-10 Published:2012-06-13
  • Contact: WAN Kang-lin E-mail:wankanglin@icdc.cn

Abstract: Objective  To determine the correlation between isoniazid resistance level and the mutations in katG, inhA promoter and oxyR-ahpC, and the correlation between rifampicin resistance level and the mutations in rpoB in Mycobacterium tuberculosisMethods  Microplate alamar blue assay was used to determine the isoniazid MIC in 59 isoniazid-resistant Mycobacterium tuberculosis clinical isolates and the rifampicin MIC in 30 rifampicin resistant isolates, and direct sequencing was used to detect the mutations of katG, inhA promoter and oxyR-ahpC in isoniazid-resistant isolates and the mutations of rpoB in rifampicin-resistant isolates.  Results  Among isoniazid-resistant isolates with MIC from 0.2500 to 1.0000 μg/ml and MIC≥2.0000 μg/ml, 7 out of 13 and 2 out of 46 isolates carried mutations in inhA promoter respectively,and 2 out of 13 and 35 out of 46 isolates carried mutation in codon katG 315 respectively, the χ2 values were 15.57 and 13.48, respectively, the P values were all 0.000. Among rifampicin-resistant isolates with MIC from 0.5000 to 16.0000 μg/ml and MIC≥32.0000 μg/ml, 5 out of 8 and 21 out of 22 isolates carried mutations in codon rpoB 531 and 526, the exact P value was 0.048.   Conclusion  Mutations in inhA promoter and katG 315 were correlated with low level and high level of isoniazid resistance respectively. rpoB mutations in codon 531 and 526 were associated with high level of rifampicin resistance.

Key words: Mycobacterium tuberculosis, Microbial sensitivity tests, Rifampin, Isoniazid, Mutation