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P. Tarlykov

National Center for Biotechnology, 13/5, Korgalzhyn road, Nur-Sultan, Kazakhstan

S. Atavliyeva

National Center for Biotechnology, 13/5, Korgalzhyn road, Nur-Sultan, Kazakhstan


 Drug-resistant tuberculosis is a global problem for humanity, especially in the countries of Southeast Asia, Eastern Europe and the CIS. In Kazakhstan, the rate of drug-resistant tuberculosis among newly diagnosed patients is more than 20%. Moreover, the Republic of Kazakhstan ranks second among the thirty countries with a high disease burden according to the World Health Organization. In this regard, it becomes obvious that it is necessary to study the nature of resistance of locally circulating strains of mycobacteria. The use of genetic typing methods will allow tracking the spread of tuberculosis pathogens of any family, which, in turn, will provide a personalized approach to treatment. The strains of the Mycobacterium tuberculosis complex capable of infecting humans include seven phylogenetic lineages, initially associated with their geographical distribution. In this study, the genomes of three drug-resistant clinical isolates of the Latin American Mediterranean family (LAM) circulating in Kazakhstan were studied. We used whole genome sequencing to study the distribution and drug resistance of isolates. Phylogenetic analysis grouped the genomes described in this study with sequences from Russia, Uzbekistan and Kazakhstan, also belonging to the LAM family. One isolate was identified as having extensive drug resistance to seven anti-TB drugs. Our results suggest that at least two drug-resistant genotypes of the LAM family are circulating in Kazakhstan. Thus, the use of genetic methods is becoming more and more popular and effective in combating the spread of tuberculosis infection.


Mycobacterium tuberculosis, genome, tuberculosis, phylogeny, DNA, mutation, antibiotic resistance

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de Almeida I.N., Vasconcellos S.E., de Assis Figueredo L.J., Dantas N.G., Augusto C.J., Hadaad J.P. Frequency of the Mycobacterium tuberculosis RD(Rio) genotype and its association with multidrug-resistant tuberculosis. BMC Infect Dis., 2019, vol. 19, no. 1, pp. 556. Crossref

Coll F., McNerney R., Guerra-Assuncao J.A., Glynn J.R., Perdigao J., Viveiros M. et al. A robust SNP barcode for typing Mycobacterium tuberculosis complex strains. Nat. Commun., 2014, vol. 5, pp. 4812. Crossref

Sola C., Filliol I., Legrand E., Mokrousov I., Rastogi N. Mycobacterium tuberculosis Phylogeny Reconstruction Based on Combined Numerical Analysis with IS1081, IS6110, VNTR, and DR-Based Spoligotyping Suggests the Existence of Two New Phylogeographical Clades. J Mol Evol., 2001, vol. 53, no. 6, pp.680-689. Crossref

van Soolingen D., Qian L., de Haas P.E., Douglas J.T., Traore H., Portaels F. et al. Predominance of a single genotype of Mycobacterium tuberculosis in countries of East Asia. J Clin Microbiol.,1995, vol.33, no. 12, pp. 3234-3288. Crossref

Stucki D., Brites D., Jeljeli L., Coscolla M., Liu Q., Trauner A. et al. Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages. Nat. Genet., 2016, vol. 48, no. 12, pp. 1535-1543. Crossref

Klotoe B.J., Kacimi S., Costa-Conceicao E., Gomes H.M., Barcellos R.B., Panaiotov S. et al. Genomic characterization of МЛУ/ШЛУ-TB in Kazakhstan by a combination of high-throughput methods predominantly shows the ongoing transmission of L2/Beijing 94-32 central Asian/Russian clusters. BMC Infect Dis., 2019, vol. 9, no. 1, pp. 553. Crossref

Lazzarini L.C., Huard R.C., Boechat N.L., Gomes H.M., Oelemann M.C., Kurepina N et al. Discovery of a novel Mycobacterium tuberculosis lineage that is a major cause of tuberculosis in Rio de Janeiro, Brazil. J Clin Microbiol., 2007, vol. 45, no. 12, pp. 3891-902. Crossref

Dubiley S., Kirillov E., Ignatova A., Stepanshina V., Shemyakin I. Molecular characteristics of the Mycobacterium tuberculosis LAM-RUS family prevalent in Central Russia. J Clin Microbiol., 2007, vol. 45, no. 12, pp. 4036-4038. Crossref

World Health Organisation. Global tuberculosis report 2019. 2019. URL: URL

Merker M., Barbier M., Cox H., Rasigade J.P., Feuerriegel S., Kohl T.A. et al. Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia. eLife, 2018, vol.7. 10.7554/eLife.38200 Crossref

Pillay M., Sturm A.W. Evolution of the Extensively Drug-Resistant F15/LAM4/KZN Strain of Mycobacterium tuberculosis in KwaZulu-Natal, South Africa. Clin Infect Dis., 2007, vol.45, no. 11, pp. 1409-1414. Crossref

Skiba Y., Mokrousov I., Ismagulova G., Maltseva E., Yurkevich N,. Bismilda V. et al. Molecular snapshot of Mycobacterium tuberculosis population in Kazakhstan: a country-wide study. Tuberculosis (Edinb), 2015, vol. 95, no.5, pp. 538-546. Crossref

Mokrousov I., Vyazovaya A., Narvskaya O. Mycobacterium tuberculosis Latin American-Mediterranean family and its sublineages in the light of robust evolutionary markers. J Bacteriol., 2014, vol. 196, no. 10, pp. 1833-41. Crossref

Skiba Y., Mokrousov I., Nabirova D., Vyazovaya A., Maltseva E., Malakhova N. et al. Mycobacterium tuberculosis RD-Rio Strain in Kazakhstan. Emerg Infect Dis., 2019, vol. 25, no.3, pp. 604-606. Crossref

Ei P.W., Aung W.W., Lee J.S., Choi G.E., Chang C.L. Molecular Strain Typing of Mycobacterium tuberculosis: a Review of Frequently Used Methods. J Korean Med Sci., 2016, vol. 31, no. 11, pp. 1673-1683. Crossref

Mokrousov I. On sunspots, click science and molecular iconography. Tuberculosis (Edinb)., 2018, vol.110, pp.91-95. Crossref

van Soolingen D., Hermans P.W., de Haas P.E., Soll D.R., van Embden J.D. Occurrence and stability of insertion sequences in Mycobacterium tuberculosis complex strains: evaluation of an insertion sequence-dependent DNA polymorphism as a tool in the epidemiology of tuberculosis. J Clin Microbiol., 1991, vol. 29, no. 11, pp. 2578-2586. Crossref

Shevtsov A., Tarlykov P., Zholdybayeva E., Shevtsova E., Momynkulov D., Sytnik I. et al. Draft Genome Sequence of the Live Vaccine Strain Brucella abortus. Genome Announc., 2013, vol. 1, no.6. Crossref

Andrews S. FastQC: a quality control tool for high throughput sequence data. URL: URL. 2019.

Nurk S., Bankevich A., Antipov D., Gurevich A.A., Korobeynikov A., Lapidus A. et al. Assembling single-cell genomes and mini-metagenomes from chimeric MDA products. Journal of computational biology: a journal of computational molecular cell biology, 2013, vol.20, no.10, pp. 714-737. Crossref