Identification of genetic markers of drug resistance based on whole genomes of clinical isolates of M.tuberculosis

Authors

  • U. A. Kozhamkulov Nazarbayev University, Private institution «National Laboratory Astana», Republic of Kazakhstan, Astana
  • U. E. Kairov Nazarbayev University, Private institution «National Laboratory Astana», Republic of Kazakhstan, Astana
  • S. E. Rakhimova Nazarbayev University, Private institution «National Laboratory Astana», Republic of Kazakhstan, Astana
  • D. A. Yerezhepov Nazarbayev University, Private institution «National Laboratory Astana», Republic of Kazakhstan, Astana
  • A. Zh. Akhmetova Nazarbayev University, Private institution «National Laboratory Astana», Republic of Kazakhstan, Astana
  • A. B. Molkenov Nazarbayev University, Private institution «National Laboratory Astana», Republic of Kazakhstan, Astana
  • A. Utyubayev Nazarbayev University, Private institution «National Laboratory Astana», Republic of Kazakhstan, Astana
  • A. R. Akilzhanova Nazarbayev University, Private institution «National Laboratory Astana», Republic of Kazakhstan, Astana
        86 44

Keywords:

tuberculosis, Mycobacterium tuberculosis, DNA, whole genome sequencing, drug resistance, mutations.

Abstract

Whole genome sequencing of 20 clinical isolated of M. tuberculosis using modern methods and instruments of next-generation sequencing. Most of the studied isolates (18) belong to Beijing family (Southern East Asian), with only two isolates were belong to T (Euro-American) and MANU-1 (Indo-Oceanic).

The genetic markers for diagnostics of drug resistant forms of tuberculosis (MDR и XDR штаммы M.tuberculosis) were studied. The analysis of genetic loci of clinical isolates of M.tuberculosis that determine the resistance to TB drugs among found genomic variants, and corresponding genes. We found from 13 to 30 genetic loci with genomic variants among whole genome data of these 20 isolates of M.tuberculosis. We found that genomic variants in four genes coding proteins of РЕ/РРЕ family and which are unique and represented only by Mycobacterium species are very specific and found only in MDR and XDR strains of mycobacteria. Proteins of this family can play a significant role as virulence factors and may contribute to the successful infection.

References

Литература

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12 Kozhamkulov U., Akhmetova A., Rakhimova S., Belova E., Alenova A., Bismilda V.,
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13 Akhmetova A, Kozhamkulov U, Bismilda V, Chingissova L, Abildaev T, Dymova M, Filipenko M, Ramanculov E Mutations in the pncA and rpsA genes among 77 Mycobacterium tuberculosis isolates in Kazakhstan. International Journal Tuberculosis and Lung Diseases 2015 Feb;19(2):179-84. DOI: 10.5588/ijtld.14.0305.
14 Ibrayeva, U. Kozhamkulov, D. Raiymbek, A. Alenova, S. Igilikova, E. Zholdybayeva, T. Abildaev, K. Momynaliev. Molecular epidemiology of Mycobacterium tuberculosis strains circulating in the penitentiary system of Kazakhstan // International Journal Tuberculosis and Lung Diseases. 2014 Mar; 18(3):298-301.DOI: 10.5588/ijtld.13.0558.
15 Skiba Y, Mokrousov I, Ismagulova G, Maltseva E, Yurkevich N, Bismilda V, Chingissova L, Abildaev T, Aitkhozhina N. Molecular snapshot of Mycobacterium tuberculosis population in Kazakhstan: A country-wide study Tuberculosis (Edinb). 2015 Sep;95(5):538-46. DOI 10.1016/j.tube.2015.04.012.
16 Ulykbek Kairov, Ulan Kozhamkulov, Askhat Molkenov, Saule Rakhimova et al. Draft Genome Sequences of Two Clinical Isolates of Mycobacterium tuberculosis from Sputum of Kazakh Patients // May/June 2015.- Volume 3 Issue 3 e00466-15. DOI:10.1128/genomeA.00466-15
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18 Banu S., Honore N., Saint-Joanis B., Philpott D., Prevost M.C., Cole S.T. Are the PE-PGRS proteins of Mycobacterium tuberculosis variable surface antigens? // Molecular microbiology. -2002. -Vol. 44, № 1. - P. 9-19. DOI: 10.1046/j.1365-2958.2002.02813.x
19 Mukhopadhyay S., Balaji K.N. The PE and PPE proteins of Mycobacterium tuberculosis // Tuberculosis. -2011. -Vol. 91, № 5. - P. 441-447. DOI: 10.1016/j.tube.2011.04.004
20 Adindla S., Guruprasad L. Sequence analysis corresponding to the PPE and PE proteins in Mycobacterium tuberculosis and other genomes // Journal of biosciences. -2003. -Vol. 28, № 2. - P. 169-179. DOI: 10.1007/BF02706216

References

1 World Health Organisation. Global tuberculosis report (2015) 20th edition, World Health Organisation, Geneva, Switzerland ISBN 978-92-4-156505-9
2 Barzon L, Lavezzo E, Militello V, Toppo S, Palu G (2011) Applications of next-generation sequencing technologies to diagnostic virology, Int J Mol Sci, 12:7861-7884. DOI: 10.3390/ijms12117861
3 Kоser CU, Ellington MJ, Cartwright EJP, Gillespie SH, Brown NM, Farrington M, Holden MTG, Dougan G, Bentley SD, Parkhill J, Peacock SJ (2012) Routine use of microbial whole genome sequencing in diagnostic and public health microbiology, PLoS Pathogen, 8 (8):1–9. DOI: 10.1371/journal.ppat.1002824
4 Hershberg R, Lipatov M, Small PM, Sheffer H, Niemann S, Homolka S, Roach JC, Kremer K, Petrov DA, Feldman MW, Gagneux S (2008) High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography, Plos Biol, 6(12): e311, 2658-2671. DOI: 10.1371/journal.pbio.0060311
5 Niemann S, Köser CU, Gagneux S, Plinke C, Homolka S, Bignell H, Carter RJ, Cheetham RK, Cox A, Gormley NA, Kokko-Gonzales P, Murray LJ, Rigatti R, Smith VP, Arends FPM, Cox HS, Smith G, Archer JAC (2009) Genomic diversity among drug sensitive and multidrug resistant isolates of Mycobacterium tuberculosis with identical DNA fingerprints, PLoS ONE, 4(10): e7407, 1-7. DOI: 10.1371/journal.pone.0007407
6 Ioerger TR, Koo S, No E-G, Chen XH, Larsen MH, Michelle H, Jacobs WR, Pillay M, Sturm AW, Sacchettini JC (2009) Genome analysis of multi- and extensively drug-resistant tuberculosis from KwaZulu-Natal, South Africa, PLoS ONE, 4(11): e7778, 1-9. DOI: 10.1371/journal.pone.0007778
7 Gardy JL, Johnston JC, Sui SJH, Sui SJH, Cook VJ, Shah LN, Brodkin E, Rempel S, Moore R, Zhao YJ, Holt R, Varhol R, Birol I, Lem M, Sharma MK, Elwood K, Jones SJM, Brinkman FSL, Brunham RC, Tang P (2011) Whole-genome sequencing and social network analysis of a tuberculosis outbreak, N Engl J Med, 364(8):730e9. DOI: 10.1056/NEJMoa1003176
8 Ford CB, Lin PL, Chase MR, Shah RR, Iartchouk O, Galagan J, Mohaideen N, Ioerger TR, Sacchettini JC, Lipsitch M, Flynn JL, Fortune SM (2011) Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection, Nat Genet, 43(5): 482e6. DOI: 10.1038/ng.811
9 Fleischmann RD, Alland D, Eisen JA, Carpenter L, White O, Peterson J, DeBoy R, Dodson R, Gwinn M, Haft D, Hickey E, Kolonay JF, Nelson WC, Umayam LA, Ermolaeva M, Salzberg SL, Delcher A, Utterback T, Weidman J, Khouri H, Gill J, Mikula A, Bishai W, Jacobs WR, Venter JC, Fraser CM (2002) Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains, J Bacteriol, 184:5479–5490. DOI: 10.1128/JB.184.19.5479-5490.2002
10 Tsolaki AG, Hirsh AE, DeRiemer K, Enciso JA, Wong MZ, Hannan M, de la Salmoniere YOL, Aman K, Kato-Maeda M, Small PM (2004) Functional and evolutionary genomics of Mycobacterium tuberculosis: insights from genomic deletions in 100 strains, Proc Natl Acad Sci USA, 101:4865–4870. DOI: 10.1073/pnas.0305634101
11 Sreevatsan S, Pan X, Stockbauer KE, Connell ND, Kreiswirth BN, Whittam TS and Musser JM (1997) Restricted structural gene polymorphism in the M. tuberculosis complex indicates evolutionarily recent global dissemination, Proc Natl Acad Sci USA, 94:9869–9874.
12 Kozhamkulov U, Akhmetova A, Rakhimova S, Belova E, Alenova A, Bismilda V, Chingissova L, Ismailov Sh, Ramanculov E, Momynaliev K (2011) Molecular characterization of rifampicin- and isoniazid-resistant Mycobacterium tuberculosis strains isolated in Kazakhstan, Japanese Journal of Infectious Disease, 64:253-255.
13 Akhmetova A, Kozhamkulov U, Bismilda V, Chingissova L, Abildaev T, Dymova M, Filipenko M, Ramanculov E (2015) Mutations in the pncA and rpsA genes among 77 Mycobacterium tuberculosis isolates in Kazakhstan. International Journal Tuberculosis and Lung Diseases, 19(2):179-84. DOI: 10.5588/ijtld.14.0305
14 Ibrayeva A, Kozhamkulov U, Raiymbek D, Alenova A, Igilikova S, Zholdybayeva E, Abildaev T, Momynaliev K (2014) Molecular epidemiology of Mycobacterium tuberculosis strains circulating in the penitentiary system of Kazakhstan, International Journal Tuberculosis and Lung Diseases, 18(3):298-301. DOI: 10.5588/ijtld.13.0558
15 Skiba Y, Mokrousov I, Ismagulova G, Maltseva E, Yurkevich N, Bismilda V, Chingissova L, Abildaev T, Aitkhozhina N (2015) Molecular snapshot of Mycobacterium tuberculosis population in Kazakhstan: A country-wide study Tuberculosis, 95(5):538-46. DOI 10.1016/j.tube.2015.04.012
16 Kairov U, Kozhamkulov U, Molkenov A, Rakhimova S, et al. (2015) Draft Genome Sequences of Two Clinical Isolates of Mycobacterium tuberculosis from Sputum of Kazakh Patients, 3 (3): e00466-15. DOI:10.1128/genomeA.00466-15
17 Van Soolingen D, de Haas PE, Hermans PW, van Embden JD (1994) DNA fingerprinting of Mycobacterium tuberculosis, Methods Enzymol, 235:196–205
18 Banu S, Honore N, Saint-Joanis B, Philpott D, Prevost MC, Cole ST (2002) Are the PE-PGRS proteins of Mycobacterium tuberculosis variable surface antigens? // Molecular microbiology, 44(1):9-19. DOI: 10.1046/j.1365-2958.2002.02813.x
19 Mukhopadhyay S, Balaji KN (2011) The PE and PPE proteins of Mycobacterium tuberculosis, Tuberculosis, 91(5):441-447. DOI: 10.1016/j.tube.2011.04.004
20 Adindla S, Guruprasad L (2003) Sequence analysis corresponding to the PPE and PE proteins in Mycobacterium tuberculosis and other genomes, Journal of biosciences, 28(2):169-179. DOI: 10.1007/BF02706216

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How to Cite

Kozhamkulov, U. A., Kairov, U. E., Rakhimova, S. E., Yerezhepov, D. A., Akhmetova, A. Z., Molkenov, A. B., Utyubayev, A., & Akilzhanova, A. R. (2016). Identification of genetic markers of drug resistance based on whole genomes of clinical isolates of M.tuberculosis. Experimental Biology, 67(2), 94–103. Retrieved from https://bb.kaznu.kz/index.php/biology/article/view/1185

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МOLECULAR BIOLOGY AND GENETICS