Mini Review
Volume 10 Issue 2 - 2021
Molecular Determinants of Isoniazid Drug Resistance Mycobacterium tuberculosis
Z Saifutdinov*, N Shadmanova, N Parpieva, V Antonenka and L Tu
National Reference Laboratory, Republican Scientific and Practical Center of Phthisiology and Pulmonology, Tashkent, Uzbekistan
*Corresponding Author: Z Saifutdinov, National Reference Laboratory, Republican Scientific and Practical Center of Phthisiology and Pulmonology, Tashkent, Uzbekistan.
Received: November 06, 2020; Published: January 30, 2021


Drug-resistant TB (TB) is a serious global problem, not only complicates the treatment of patients with resistant strains of TB, but also poses a threat to the global process to achieve the goals of the TB elimination strategy in the world by the World Health Organization (WHO) [1]. WHO estimates that 1.674 million people died of tuberculosis in 2016 alone, while between 2000 and 2016 they were healed 52.5 million lives thanks to improved diagnosis and treatment. At the same time, 13 of the 22 highest burden countries failed to meet the target for the decline in tuberculosis prevalence in 2014, highlighting the need to improve strategies to combat the disease [2]. Effective TB control is especially challenging among patients with multidrug-resistant TB (MDR-TB), which are resistant to at least isoniazid and rifampicin, the two most potent anti-TB drugs used in standard first-line treatment. For example, 2015 data show that by the end of 2014, 153 countries had reported the circulation of drug-resistant TB strains in the region, eighty of which have continuous surveillance systems, while others rely on epidemiological surveys. In the absence of an effective vaccine against tuberculosis, appropriate antibiotic therapy remains the most important tool in the fight against the spread of tuberculosis. N on at the same time, the factors of resistance, greatly exacerbating transmission from TB that are resistant to the first drug and the second line and show the importance of broader molecular genetic research in this area [1-5].

Keywords: Tuberculosis; Drug Resistance; Molecular Mechanisms of Development of Mycobacterial Resistance; Gene Mutations


  1. World Health Organization. WHO Consolidated Guidelines on Drug Resistant Tuberculosis Treatment. Geneva, Switzerland: WHO (2019).
  2. Global tuberculosis report. World Health Organization, Geneva, Switzerland (2017).
  3. World Health Organization. Global Tuberculosis Report (2018).
  4. Forrellad MA., et al. “Virulence factors of the Mycobacterium tuberculosis complex”. Virulence 1 (20013): 3-66.
  5. Nguyen L. “Antibiotic resistance mechanisms in M. tuberculosis an update”. Archives of Toxicology 90 (2016): 1585-604.
  6. Savinova AA and Usanina LV. “The mechanisms of antibiotic resistance of Mycobacterium tuberculosis”. International Student Scientific Bulletin (2017): 6.
  7. Chernyaeva EN. “Biochemical mechanisms of drug resistance of Mycobacterium tuberculosis”. Saint Petersburg State University Bulletin 2 (2012): 77-91.
  8. Jagielski T., et al. “Mutation profiling for detection of isoniazid resistance in Mycobacterium tuberculosis clinical isolates”. Journal of Antimicrobial Chemotherapy 70 (2015): 3214-3221.
  9. Jagielski T., et al. “Identification and analysis of mutations in the katG gene in multidrug-resistant Mycobacterium tuberculosis clinical isolates”. Pneumonologia i Alergologia Polska 81 (2013): 298-307.
  10. Zhang Y., et al. “The catalase-β-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis”. Nature 358 (1992): 591-593.
  11. Timmins GS and Deretic V. “Mechanisms of action of isoniazid”. Molecular Microbiology 62 (2006): 1220-1227.
  12. Seifer M., et al. “Genetic mutations associated with isoniazid resistance in Mycobacterium tuberculosis: a systematic review”. PloS one 10 (2015): e0119628.
  13. Böttger EC. In Antituberculosis Chemotherapy Volume 40 (eds PR Donald and PD van Helden) Chapter 14 (2011): 128-144.
  14. Vilcheze C and Jacobs WR. “Resistance to isoniazid and ethionamide in Mycobacterium tuberculosis: genes, mutations, and causalities”. Microbiology Spectrum 2 (2013).
  15. Pauline Lempens., et al. “Isoniazid resistance levels of Mycobacterium tuberculosis can largely be predicted by high confidence resistance-conferring Mutations”. Scientific Reports 8 (2018): 3246.
  16. Coll F., et al. “Genome-wide analysis of multi-and extensively drug-resistant Mycobacterium tuberculosis”. Nature Genetics 50 (2018): 307.
  17. Demay C., et al. “SITVITWEB - a publicly available international multimarker database for studying Mycobacterium tuberculosis genetic diversity and molecular epidemiology”. Infection, Genetics and Evolution 4 (2012): 755-766.
  18. Liu L., et al. “The impact of combined gene mutations in inhA and ahpC genes on high levels of isoniazid resistance amongst katG non-315 in multidrug-resistant tuberculosis isolates from China”. Emerg Microbes Infect1 (2018): 183.
  19. Brossier F., et al. “Comparison of a semiautomated commercial repetitive-sequence-based PCR method with spoligotyping, 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat typing, and restriction fragment length polymorphism-based analysis of IS6110 for Mycobacterium tuberculosis typing”. Journal of Clinical Microbiology 11 (2014): 4082-4086.
  20. Zhdanova SN., et al. “Epidemiological substantiation of the distribution of the main clones of the Beijing Mycobacterium tuberculosis genotype in the Irkutsk region”. Journal Mikrobiol Ogii 6 (2017): 88-94.
  21. Casali N., et al. “Evolution and transmission of drug-resistant tuberculosis in a Russian population”. Nature Genetics 3 (2014): 279-286.
  22. De Keijzer J., et al. “Disclosure of selective advantages in the "modern" sublineage of the 134 Mycobacterium tuberculosis Beijing genotype family by quantitative proteomics”. Molecular and Cellular Proteomics 10 (2014): 2632-2645.
  23. VV Sinkov. "Molecular-epidemiological analysis of experimental data on the example of the genotype". Beijing "(Beijing) Mycobacterium tuberculosis (2012).
  24. Surkova LK., et al. “Molecular genetic characteristics of the causative agent of tuberculosis: relationship with the prevalence, course and outcome of the disease. Vesti National Academy of Sciences of Belarus”. Gray Medytsyn Navuk 4 (2016): 114-125.
  25. Bostanabad ZS., et al. “KatG mutations in isoniazid-resistant strains of Mycobacterium tuberculosis isolates from Belarusian patients”. Tuberkuloz ve Toraks 3 (2007): 231-237.
  26. Dymova MA., et al. “Molecular genetic characteristics of M. tuberculosis effluents in patients with pulmonary tuberculosis in Astana”. SB RAMS Bulletin1 (2011): 107-112.
  27. Akhmetova AZh., et al. “Molekulyarnaya characteristic multiresistant strains of M. tuberculosis , circulating in Kazakhstan”. Science and Health21 (2019): 45-52.
  28. C Allen., et al. “Molekulyarno - genetic analysis and cn e CTD mutations in genes katG, inhA, rpo B, encoding drug resistance to isoniazid and rifampicin in patients with tuberculosis and HIV infection”. Tuberculosis and Lung Diseases8 (2016): 54-59.
  29. Hasker E., et al. “The practice of prescribing anti-tuberculosis drugs in Uzbekistan”. International Journal of Tuberculosis and Lung Diseases1 (2011): 135-142.
Citation: Z Saifutdinov., et al. “Molecular Determinants of Isoniazid Drug Resistance Mycobacterium tuberculosis”. EC Pulmonology and Respiratory Medicine 10.2 (2021): 63-68.

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