Genetic mutations associated with isoniazid resistance in mycobacterium tuberculosis in Mongolia

Erdenegerel Narmandakh, Oyuntuya Tumenbayar, Tsetsegtuya Borolzoi, Baasansuren Erkhembayar, Tsolmon Boldoo, Naranzul Dambaa, Buyankhishig Burneebaatar, Naranbat Nymadawa, Satoshi Mitarai, Sarantuya Jav, Chen Yuan Chiang

Research output: Contribution to journalArticle

Abstract

Globally, mutations in the katG gene account for the majority of isoniazidresistant strains of Mycobacterium tuberculosis. Buyankhishig et al. analyzed a limited number of Mycobacterium tuberculosis strains in Mongolia and found that isoniazid resistance was mainly attributable to inhA mutations (B. Buyankhishig, T. Oyuntuya, B. Tserelmaa, J. Sarantuya, et al., Int J Mycobacteriol 1:40-44, 2012, https://doi.org/10.1016/j.ijmyco.2012.01.007). The GenoType MTBDRplus assay was performed for isolates collected in the First National Tuberculosis Prevalence Survey and the Third Anti- Tuberculosis Drug Resistance Survey to investigate genetic mutations associated with isoniazid resistance in Mycobacterium tuberculosis in Mongolia. Of the 409 isoniazidresistant isolates detected by the GenoType MTBDRplus assay, 127 (31.1%) were resistant to rifampin, 294 (71.9%) had inhA mutations without katG mutations, 113 (27.6%) had katG mutations without inhA mutations, and 2 (0.5%) had mutations in both the inhA and katG genes. Of the 115 strains with any katG mutation, 114 (99.1%) had mutations in codon 315 (S315T). Of the 296 strains with any inhA mutation, 290 (98.0%) had a C15T mutation. The proportions of isoniazid-resistant strains with katG mutations were 25.3% among new cases and 36.2% among retreatment cases (P=0.03) and 17.0% among rifampin-susceptible strains and 52.8% among rifampinresistant strains (P<0.01). Rifampin resistance was significantly associated with the katG mutation (adjusted odds ratio, 5.36; 95% confidence interval [CI], 3.3 to 8.67, P<0.001). Mutations in inhA predominated in isoniazid-resistant tuberculosis in Mongolia. However, the proportion of katG mutations in isolates from previously treated cases was higher than in those from new cases, and the proportion in cases with rifampin resistance was higher than in cases without rifampin resistance.

Original languageEnglish
Article numbere00537-20
JournalAntimicrobial Agents and Chemotherapy
Volume64
Issue number7
DOIs
Publication statusPublished - Jul 2020

Keywords

  • Drug resistance
  • InhA
  • KatG
  • Mutation
  • Mycobacterium tuberculosis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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  • Cite this

    Narmandakh, E., Tumenbayar, O., Borolzoi, T., Erkhembayar, B., Boldoo, T., Dambaa, N., Burneebaatar, B., Nymadawa, N., Mitarai, S., Jav, S., & Chiang, C. Y. (2020). Genetic mutations associated with isoniazid resistance in mycobacterium tuberculosis in Mongolia. Antimicrobial Agents and Chemotherapy, 64(7), [e00537-20]. https://doi.org/10.1128/AAC.00537-20