Mycobacterium tuberculosis Transcriptome Profiling in Mice with Genetically Different Susceptibility to Tuberculosis

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Abstract


Whole transcriptome profiling is now almost routinely used in various fields of biology, including microbiology. In vivo transcriptome studies usually provide relevant information about the biological processes in the organism and thus are indispensable for the formulation of hypotheses, testing, and correcting. In this study, we describe the results of genome-wide transcriptional profiling of the major human bacterial pathogen M. tuberculosis during its persistence in lungs. Two mouse strains differing in their susceptibility to tuberculosis were used for experimental infection with M. tuberculosis. Mycobacterial transcriptomes obtained from the infected tissues of the mice at two different time points were analyzed by deep sequencing and compared. It was hypothesized that the changes in the M. tuberculosis transcriptome may attest to the activation of the metabolism of lipids and amino acids, transition to anaerobic respiration, and increased expression of the factors modulating the immune response. A total of 209 genes were determined whose expression increased with disease progression in both host strains (commonly upregulated genes, CUG). Among them, the genes related to the functional categories of lipid metabolism, cell wall, and cell processes are of great interest. It was assumed that the products of these genes are involved in M. tuberculosis adaptation to the host immune system defense, thus being potential targets for drug development.


T. A. Skvortsov

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry

Author for correspondence.
Email: timofey@ibch.ru

Russian Federation

D. V. Ignatov

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry

Email: timofey@ibch.ru

Russian Federation

K. B. Majorov

Central Institute for Tuberculosis

Email: timofey@ibch.ru

Russian Federation

A. S. Apt

Central Institute for Tuberculosis

Email: timofey@ibch.ru

Russian Federation

T. L. Azhikina

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry

Email: timofey@ibch.ru

Russian Federation

  1. Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C., Harris D., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. 3rd // Nature 1998, V.393, №6685, P.537-544
  2. Wilson M., DeRisi J., Kristensen H.H., Imboden P., Rane S., Brown P.O., Schoolnik G.K. // Proc. Natl. Acad. Sci. USA. 1999, V.96, №22, P.12833-12838
  3. Butcher P.D. // Tuberculosis (Edinb.). 2004, V.84, №3-4, P.131-137
  4. Kendall S.L., Rison S.C., Movahedzadeh F., Frita R., Stoker N.G. // Trends Microbiol. 2004, V.12, №12, P.537-544
  5. Skvortsov T.A., Azhikina T.L. // Russian Journal of Bioorganic Chemistry. 2010, V.36, №5, P.550-559
  6. Skvortsov T.A., Azhikina T.L. // ssian Journal of Bioorganic Chemistry. 2012, V.38, №4, P.391-405
  7. Ignatov D.V., Skvortsov T.A., Majorov K.B., Apt A.S., Azhikina T.L. // Acta Naturae 2010, V.2, №3, P.78-84
  8. Azhikina T.L., Skvortsov T.A., Radaeva T.V., Mardanov A.V., Ravin N.V., Apt A.S., Sverdlov E.D. // Biotechniques. 2010, V.48, №2, P.139-144
  9. Audic S., Claverie J.M. // Genome Res. 1997, V.7, №10, P.986-995
  10. Kondratieva E., Logunova N., Majorov K., Averbakh M., Apt A. // PLoS One 2010, V.5, №5, P.e10515
  11. Arnvig K., Young D. // RN A Biology 2012, V.9, №4, P.427-436
  12. Arnvig K.B., Comas I., Thomson N.R., Houghton J., Boshoff H.I., Croucher N.J., Rose G., Perkins T.T., Parkhill J., Dougan G. // PLoS Pathog. 2011, V.7, №11, P.e1002342
  13. Sassetti C.M., Boyd D.H., Rubin E.J. // Mol. Microbiol. 2003, V.48, №1, P.77-84
  14. Shi L., Sohaskey C.D., Kana B.D., Dawes S., North R.J., Mizrahi V., Gennaro M.L. // Proc. Natl. Acad. Sci. USA. 2005, V.102, №43, P.15629-15634
  15. Stokes R.W., Waddell S.J. // Future Microbiol. 2009, V.4, №10, P.1317-1335
  16. Waddell S.J. // Drug Discov. Today: Dis. Mech. 2010, V.7, №1, P.e61-e73
  17. Karboul A., Mazza A., Gey van Pittius N.C., Ho J.L., Brousseau R., Mardassi H. // Journal of Bacteriology 2008, V.190, №23, P.7838-7846
  18. Hinchey J., Jeon B.Y., Alley H., Chen B., Goldberg M., Derrick S., Morris S., Jacobs W.R., Jr. I.O., Porcelli S.A., Lee S. // PLoS One 2011, V.6, №1, P.e15857
  19. Homolka S., Niemann S., Russell D.G., Rohde K.H. // PLoS Pathog. 2010, V.6, №7, P.e1000988
  20. Ward S.K., Abomoelak B., Marcus S., Talaat A.M. // Front. Microbiol. 2010, V.1, P.121
  21. Raman K., Vashisht R., Chandra N. // Mol. BioSystems 2009, V.5, №12, P.1740-1751
  22. Raman K., Yeturu K., Chandra N. // BMC Systems Biol. 2008, V.2, №1, P.109
  23. Kalapanulak S. // High quality genome-scale metabolic network reconstruction of mycobacterium tuberculosis and comparison with human metabolic network: application for drug targets identification. Edinburgh: Univ. of Edinburgh 2009
  24. Nisa S.Y. // ParA: a novel target for anti-tubercular drug discovery // Wellington: Victoria Univ. of Wellington 2010
  25. Srivastava V., Jain A., Srivastava B.S., Srivastava R. // Tuberculosis 2008, V.88, №3, P.171-177
  26. Srivastava V., Rouanet C., Srivastava R., Ramalingam B., Locht C., Srivastava B.S. // Microbiology 2007, V.153, №3, P.659-666
  27. Boshoff H.I.M., Myers T.G., Copp B.R., McNeil M.R., Wilson M.A., Barry C.E. // J. Biol. Chem. 2004, V.279, №38, P.40174-4014
  28. Shi T., Fu T., Xie J. // Curr. Microbiology 2011, V.63, №5, P.470-476

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Copyright (c) 2013 Skvortsov T.A., Ignatov D.V., Majorov K.B., Apt A.S., Azhikina T.L.

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