Skip to main content
SpringerLink
Log in

cAMP-Dependent Transcription Factor in Mycobacterium tuberculosis Coded by the Rv3676 Gene as a Possible Target for the Development of Antituberculosis Drugs

  • Published:
Applied Biochemistry and Microbiology Aims and scope Submit manuscript

Abstract

Adenylate cyclase Rv2212 plays a key role in the growth of Mycobacterium tuberculosis (Mtb) and its reactivation from the dormant state. This enzyme could potentially be a good target for the development of new antituberculosis drugs. However, enzymes of this type are also important for the metabolism of the host organism, which makes it doubtful that their inhibitors can be used for treatment of the disease. In the Mtb genome, the cAMP-dependent transcription factor (cAMP-TF), which is encoded by the Rv3676 gene, is annotated and absent in the human organism. The Mtb strain with an overexpression of this gene was designed. This strain rapidly grew in vitro and in vivo under stress conditions. Bacteria of the new strain retained the plasmid with the Rv3676 gene in vivo even in the absence of a selection agent, which indicated the advantages for survival with increased cAMP-TF expression. These results demonstrate the importance of Rv3676 for maintenance of the viability of Mtb cells under unfavorable in vitro conditions and their virulence in vivo and were similar to those obtained by overexpression of the adenylate cyclase Rv2212. Transcription factor Rv3676 may be a new target for the development of new antituberculosis drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.

Similar content being viewed by others

REFERENCES

  1. Barry, C.E., Boshoff, H., Dartois, V., Dick, T., Ehrt, S., Flynn, J., Schnappinger, D., Wilkinson, R.J., and Young, D., Nat. Rev. Microbiol., 2009, vol. 7, no. 12, pp. 845–855.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Shleeva, M.O., Kudykina, Y.K., Vostroknutova, G.N., Suzina, N.E., Mulyukin, A.L., and Kaprelyants, A.S., Tuberculosis, 2011, vol. 91, no. 2, pp. 146–154.

    Article  CAS  PubMed  Google Scholar 

  3. Shleeva, M.O., Bagramyan, K., Telkov, M.V., Mukamolova, G.V., Young, M., Kell, D.B., and Kaprelyants, A.S., Microbiology, 2002, vol. 148, no. 5, pp. 1581–1591.

    Article  CAS  PubMed  Google Scholar 

  4. Shleeva, M., Goncharenko, A., Kudykina, Y., Young, D., Young, M., and Kaprelyants, A., PLoS One, 2013, vol. 8, no. 12. e82914.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Motaal, A.A., Tews, I., Schultz, J.E., and Linder, J.U., FEBS J., 2006, vol. 273, no. 18, pp. 4219–4228.

    Article  CAS  PubMed  Google Scholar 

  6. Knapp, G.S. and McDonough, K.A., Microbiol. Spectr., 2014, vol. 2, no. 2, pp. 1–14.

    Article  CAS  Google Scholar 

  7. Shleeva, M.O., Kondratieva, T.K., Demina, G.R., Rubakova, E.I., Goncharenko, A.V., Apt, A.S., and Kaprelyants, A.S., Front. Cell. Infect. Microbiol, 2017, vol. 7, no. 370. https://doi.org/10.3389/fcimb.2017.00370

  8. Baker, D.A. and Kelly, J.M., Mol. Microbiol., 2004, vol. 52, no. 5, pp. 1229–1242.

    Article  CAS  PubMed  Google Scholar 

  9. Nikitushkin, V.D., Demina, G.R., and Kaprelyants, A.S., Biochemistry (Moscow), 2016, vol. 81, no. 13, pp. 1719–1734.

    CAS  PubMed  Google Scholar 

  10. Connell, N.D., Methods Cell Biol., 1994, vol. 45, no. 6, pp. 107–125.

    Article  CAS  PubMed  Google Scholar 

  11. Mukamolova, G., Turapov, O., Young, D.I., Kaprelyants, A.S., Kell, D.B., and Young, M., Mol. Microbiol., 2002, vol. 46, no. 3, pp. 623–635.

    Article  CAS  PubMed  Google Scholar 

  12. Drancourt, M. and Raoult, D., PLoS Negl. Trop. Dis., vol. 1, no. 2. e83.

  13. Nikonenko, B.V., Averbakh, M.M., Apt, A.S., Lavebratt, C., and Schurr, E., Tuber. Lung Dis., vol. 80, no. 1, pp. 15–25.

  14. Kalamidas, S.A., Kuehnel, M.P., Peyron, P., Rybin, V., Rauch, S., Kotoulas, O.B., Houslay, M., Hemmings, B.A., Maximiliano, G., Gutierrez, M.G., Anes, E., and Griffiths, G., J. Cell Sci., 2006, vol. 119, no. 17, pp. 3686–3694.

    Article  CAS  PubMed  Google Scholar 

  15. Agarwal, N., Lamichhane, G., Gupta, R., Nolan, S., and Bishai, W.R., Nature, 2009, vol. 460, no. 7251, pp. 98–102.

    Article  CAS  PubMed  Google Scholar 

  16. Gazdik, M.A. and McDonough, K.A., J. Bacteriol., 2005, vol. 187, no. 8, pp. 2681–2692.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pedroza-Roldán, C., de Jesús Aceves-Sánchez, M., Zaveri, A., Charles-Niño, C., Elizondo-Quiroga, D.E., Hernández-Gutiérrez, R., Allen, K., and Visweswariah, S., Folia Microbiol., 2015, vol. 60, pp. 21–31.

    Article  CAS  Google Scholar 

  18. Rickman, L., Scott, C., Hunt, D.M., Hutchinson, T., Menendez, M.C., Whalan, R., Hinds, J., Colston, M.J., Green, J., and Buxton, R.S., Mol. Microbiol., 2010, vol. 56, no. 5, pp. 1274–1286.

    Article  CAS  Google Scholar 

Download references

Funding

This study was financially supported by the Russian Science Foundation (project no. 16-15-00245, in-vitro experiments) and by the Russian Foundation for Basic Research (project no. 17-04-00119А, in-vivo experiments).

Author information

Authors and Affiliations

  1. Bach Institute of Biochemistry, Federal Research Center of Biotechnology, Russian Academy of Sciences, 119071, Moscow, Russia

    M. O. Shleeva, A. V. Goncharenko & A. S. Kaprelyants

  2. Department of Immunology, Laboratory for Immunogenetics, Central Institute for Tuberculosis, 107564, Moscow, Russia

    T. K. Kondratieva & A. S. Apt

  3. Department of Immunology, School of Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    A. S. Apt

Authors
  1. M. O. Shleeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. K. Kondratieva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. V. Goncharenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. S. Apt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. S. Kaprelyants
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. O. Shleeva.

Ethics declarations

The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

Additional information

Translated by P. Vikhreva

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shleeva, M.O., Kondratieva, T.K., Goncharenko, A.V. et al. cAMP-Dependent Transcription Factor in Mycobacterium tuberculosis Coded by the Rv3676 Gene as a Possible Target for the Development of Antituberculosis Drugs. Appl Biochem Microbiol 55, 380–385 (2019). https://doi.org/10.1134/S0003683819030128

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0003683819030128

Keywords:

Search

Navigation