Thanks to visit codestin.com
Credit goes to link.springer.com

Skip to main content
Springer Nature Link
Log in

The Actinobacterial mce Operon: Structure and Functions

  • Published:
Biology Bulletin Reviews Aims and scope Submit manuscript

Abstract

The results of studies on mce operons of the causative agent Mycobacterium tuberculosis and actinobacteria are summarized. Mce transporters belong to a group of cell-wall proteins. The genome of M. tuberculosis contains four mce operons that encode complexes, each of which consists of two integral membrane proteins (YrbEB) followed by six other Mce proteins (MceA–F). These proteins are functionally similar to ABC transporters. Despite their significant role in the pathogenesis of M. tuberculosis infection, Mce proteins remain poorly studied due to their complex structure and operon regulation. However, a number of their functions have been characterized; they include the penetration of host cells by M. tuberculosis and its survival, as well as the transport of cholesterol and mycolic acids, which are pathogenicity factors of no small importance. The expression of mce operons depends on many factors, such as the growth phase, the culture medium, and the localization of M. tuberculosis infection. Today, strains of M. tuberculosis and M. bovis with deleted mce operons are considered candidates for the development of new attenuated vaccines that might one day replace the M. bovis BCG vaccine, which is no longer deemed strong enough to hold back the tuberculosis epidemic.

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

Access this article

Log in via an institution

Subscribe and save

Springer+
from £29.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Explore related subjects

Discover the latest articles, books and news in related subjects, suggested using machine learning.

REFERENCES

  1. Ahmad, S., El-Shazly, S., Mustafa, A.S., et al., Mammalian cell-entry proteins encoded by the mce3 operon of Mycobacterium tuberculosis are expressed during natural infection in humans, Scand. J. Immunol., 2004, vol. 60, no. 4, pp. 382–391.

    Article  CAS  PubMed  Google Scholar 

  2. Ahmad, S., El-Shazly, S., Mustafa, AS., et al., The six mammalian cell entry proteins (Mce3A-F) encoded by the mce3 operon are expressed during in vitro growth of Mycobacterium tuberculosis,Scand. J. Immunol., 2005, vol. 62, no. 1, pp. 16–24.

    Article  CAS  PubMed  Google Scholar 

  3. Arruda, S., Bomfim, G., Knights, R., et al., Cloning of an M. tuberculosis DNA fragment associated with entry and survival inside cells, Science, 1993, vol. 261, no. 5127, pp. 1454–1457.

    Article  CAS  PubMed  Google Scholar 

  4. Beste, D.J.V., Espasa, M., Bonde, B., et al., The genetic requirements for fast and slow growth in mycobacteria, PLoS One, 2009, vol. 4, p. e5349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Casali, N. and Riley, L.W., A phylogenomic analysis of the actinomycetales mce operons, BMC Genomics, 2007, vol. 26, no. 8, p. 60.

    Article  CAS  Google Scholar 

  6. Chitale, S., Ehrt, S., Kawamura, I., et al., Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry, Cell. Microbiol., 2001, vol. 3, no. 4, рр. 247–254

    Article  CAS  PubMed  Google Scholar 

  7. Cole, S.T., Brosch, R., Parkhill, J., et al., Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence, Nature, 1998, vol. 393, no. 6685, pp. 537–544.

    Article  CAS  PubMed  Google Scholar 

  8. Cosate, M.R., Siqueira, G.H., de Souza, G.O., et al., Mammalian cell entry (Mce) protein of Leptospira interrogans binds extracellular matrix components, plasminogen and β2 integrin, Microbiol. Immunol., 2016, vol. 60, no. 9, pp. 586–598.

    Article  CAS  PubMed  Google Scholar 

  9. Dunphy, K.Y., Senaratne, R.H., Masuzawa, M., et al., Attenuation of Mycobacterium tuberculosis functionally disrupted in a fatty acyl-coenzyme A synthetase gene fadD5, J. Infect. Dis., 2010, vol. 201, pp. 1232–1239.

    Article  CAS  PubMed  Google Scholar 

  10. El-Shazly, S., Ahmad, S., Mustafa, A.S., et al., Internalization by HeLa cells of latex beads coated with mammalian cell entry (Mce) proteins encoded by the mce3 operon of Mycobacterium tuberculosis,J. Med. Microbiol., 2007, vol. 56, no. 9, pp. 1145–1151.

    Article  CAS  PubMed  Google Scholar 

  11. Forrellad, M.A., Klepp, L.I., Gioffre, A., et al., Virulence factors of the Mycobacterium tuberculosis complex, Virulence, 2013, vol. 4, no. 1, pp. 3–66.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Forrellad, M.A., McNeil, M., Santangelo, M.L., et al., Role of the Mce1 transporter in the lipid homeostasis of Mycobacterium tuberculosis,Tuberculosis (Edinburgh), 2014, vol. 94, no. 2, pp. 170–177.

    Article  CAS  PubMed  Google Scholar 

  13. García, E., Bianco, M.V., Blanco, F.C., et al., Mycobacterium bovis deleted in mce2 and phoP loci protects C57BL/6 mice against tuberculosis, J. Infect. Dev. Countries, 2016, vol. 10, no. 8, pp. 892–894.

    Article  Google Scholar 

  14. García-Fernández, J., Papavinasasundaram, K., Galán, B., et al., Molecular and functional analysis of the mce4 operon in Mycobacterium smegmatis,Environ. Microbiol., 2017, vol. 19, no. 9, pp. 3689–3699.

    Article  CAS  PubMed  Google Scholar 

  15. Ghosh, P., Hsu, C., Alyamani, E.J., et al., Genome-wide analysis of the emerging infection with Mycobacterium avium subspecies paratuberculosis in the Arabian camels (Camelus dromedarius), PLoS One, 2012, vol. 7, no. 2, p. e31947.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gioffré, A., Infante, E., Aguilar, D., et al., Mutation in mce operons attenuates Mycobacterium tuberculosis virulence, Microb. Infect. Inst. Pasteur, 2005, vol. 7, pp. 325–334.

    Article  CAS  Google Scholar 

  17. Global Tuberculosis Report 2017, Geneva: World Health Org., 2019.

  18. Hemati, Z., Derakhshandeh, A., Haghkhah, M., et al., Mammalian cell entry operons; novel and major subset candidates for diagnostics with special reference to Mycobacterium avium subspecies paratuberculosis infection, Vet. Quart., 2019, vol. 39, no. 1, pp. 65–75.

    Article  CAS  Google Scholar 

  19. Khan, S., Islam, A., Hassan, M.I., et al., Purification and structural characterization of Mce4A from Mycobacterium tuberculosis,Int. J. Biol. Macromol., 2016, vol. 93, pp. 235–241.

    Article  CAS  PubMed  Google Scholar 

  20. Kumar, A., Bose, M., and Brahmachari, V., Analysis of expression profile of mammalian cell entry (mce) operons of Mycobacterium tuberculosis,Infect. Immun., 2003, vol. 71, no. 10, pp. 6083–6087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lange, C., Chesov, D., Heyckendorf, J., et al., Drug-resistant tuberculosis: an update on disease burden, diagnosis and treatment, Respirology, 2018, vol. 23, no. 7, pp. 656–673.

    Article  PubMed  Google Scholar 

  22. Lu, S., Tager, L.A., Chitale, S., and Riley, L.W., A cell-penetrating peptide derived from mammalian cell uptake protein of Mycobacterium tuberculosis,Anal. Biochem., 2006, vol. 353, no. 1, pp. 7–14.

    Article  CAS  PubMed  Google Scholar 

  23. Marimani, M., Ahmad, A., and Duse, A., The role of epigenetics, bacterial and host factors in progression of Mycobacterium tuberculosis infection, Tuberculosis (Edinburgh), 2018, vol. 113, pp. 200–214.

    Article  CAS  PubMed  Google Scholar 

  24. Marjanovic, O., Iavarone, A.T., and Riley, L.W., Sulfolipid accumulation in Mycobacterium tuberculosis disrupted in the mce2 operon, J. Microbiol., 2011, vol. 49, no. 3, pp. 441–447.

    Article  CAS  PubMed  Google Scholar 

  25. Marjanovic, O., Miyata, T., Goodridge, A., et al., Mce2 operon mutant strain of Mycobacterium tuberculosis is attenuated in C57BL/6 mice, Tuberculosis (Edinburgh), 2010, vol. 90, no. 1, pp. 50–56.

    Article  CAS  PubMed  Google Scholar 

  26. Mikheecheva, N.E., Zaychikova, M.V., Melerzanov, A.V., et al., A nonsynonymous SNP catalog of Mycobacterium tuberculosis virulence genes and its use for detecting new potentially virulent sublineages, Gen. Biol. Evol., 2017, vol. 9, no. 4, pp. 887–899.

    Article  CAS  Google Scholar 

  27. Miller, C.D., Hall, K., Liang, Y.N., et al., Isolation and characterization of polycyclic aromatic hydrocarbon-degrading Mycobacterium isolates from soil, Microb. Ecol., 2004, vol. 48, no. 2, pp. 230–238.

    Article  CAS  PubMed  Google Scholar 

  28. Mitra, D., Saha, B., Das, D., et al., Correlating sequential homology of Mce1A, Mce2A, Mce3A and Mce4A with their possible functions in mammalian cell entry of Mycobacterium tuberculosis performing homology modeling, Tuberculosis (Edinburgh), 2005, vol. 85, nos. 5–6, pp. 337–345.

    Article  CAS  PubMed  Google Scholar 

  29. Mohn, W.W., van der Geize, R., Stewart, G.R., et al., The actinobacterial mce4 locus encodes a steroid transporter, J. Biol. Chem., 2008, vol. 283, no. 51, pp. 35368–35374.

    Article  CAS  PubMed  Google Scholar 

  30. Nakayama, T. and Zhang-Akiyama, Q.M., pqiABC and yebST, putative mce operons of Escherichia coli, encode transport pathways and contribute to membrane integrity, J. Bacteriol., 2016, vol. 199, no. 1, p. e00606-16.

    PubMed  PubMed Central  Google Scholar 

  31. Pagliarulo, C., Salvatore, P., De Vitis, L.R., et al., Regulation and differential expression of gdhA encoding NADP-specific glutamate dehydrogenase in Neisseria meningitidis clinical isolates, Mol. Microbiol., 2004, vol. 51, no. 6, pp. 1757–1772.

    Article  CAS  PubMed  Google Scholar 

  32. Parker, S.L., Tsai, Y.L., and Palmer, C.J., Comparison of PCR-generated fragments of the mce gene from Mycobacterium tuberculosis, M. avium, M. intracellulare, and M. scrofulaceum,Clin. Diagn. Lab. Immunol., 1995, vol. 2, no. 6, pp. 770–775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Pasricha, R., Chandolia, A., Ponnan, P., et al., Single nucleotide polymorphism in the genes of mce1 and mce4 operons of Mycobacterium tuberculosis: analysis of clinical isolates and standard reference strains, BMC Microbiol., 2011, vol. 11, p. 41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Prozorov, A.A., Fedorova, I.A., Bekker, O.B., et al., The virulence factors of Mycobacterium tuberculosis: genetic control, new conceptions, Russ. J. Genet., 2014, vol. 50, no. 8, pp. 775–797.

    Article  CAS  Google Scholar 

  35. Qiang, L., Wang, J., Zhang, Y., et al., Mycobacterium tuberculosis Mce2E suppresses the macrophage innate immune response and promotes epithelial cell proliferation, Cell Mol. Immunol., 2019, vol. 16, no. 4, pp. 380–391.

    Article  CAS  PubMed  Google Scholar 

  36. Queiroz, A., Medina-Cleghorn, D., Marjanovic, O., et al., Comparative metabolic profiling of mce1 operon mutant vs wild-type Mycobacterium tuberculosis strains, Pathog. Dis., 2015, vol. 73, no. 8, art. ID ftv066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ribeiro, S.C., Gomes, L.L., Amaral, E.P., et al., Mycobacterium tuberculosis strains of the modern sublineage of the Beijing family are more likely to display increased virulence than strains of the ancient sublineage, J. Clin. Microbiol., 2014, vol. 52, pp. 2615–2624.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Rodríguez, D.C., Ocampo, M., Varela, Y., et al., Mce4F Mycobacterium tuberculosis protein peptides can inhibit invasion of human cell lines, Pathog. Dis., 2015, vol. 73, no. 3, art. ID ftu020.

    Article  CAS  PubMed  Google Scholar 

  39. Saini, N.K., Sharma, M., Chandolia, A., et al., Characterization of Mce4A protein of Mycobacterium tuberculosis: role in invasion and survival, BMC Microbiol., 2008, vol. 8, no. 1, p. 200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Santangelo, M.P., Blanco, F.C., Bianco, M.V., et al., Study of the role of Mce3R on the transcription of mce genes of Mycobacterium tuberculosis,BMC Microbiol., 2008, vol. 8, no. 1, p. 38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Shimono, N., Morici, L., Casali, N., et al., Hypervirulent mutant of Mycobacterium tuberculosis resulting from disruption of the mce1 operon, Proc. Natl. Acad. Sci. U.S.A., 2003, vol. 100, pp. 15 918–1592.

    Article  CAS  Google Scholar 

  42. Singh, P., Katoch, V.M., Mohanty, K.K., et al., Analysis of expression profile of mce operon genes (mce1, mce2, mce3 operon) in different Mycobacterium tuberculosis isolates at different growth phases, Indian J. Med. Res., 2016, vol. 143, no. 4, pp. 487–494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Stavrum, R., Valvatne, H., Stavrum, A.-K., et al., Mycobacterium tuberculosis Mce1 protein complex initiates rapid induction of transcription of genes involved in substrate trafficking, Genes Immun., 2012, vol. 13, no. 6, pp. 496–502.

    Article  CAS  PubMed  Google Scholar 

  44. Timms, V.J., Hassan, K.A., Mitchell, H.M., et al., Comparative genomics between human and animal associated subspecies of the Mycobacterium avium complex: a basis for pathogenicity, BMC Genomics, 2015, vol. 16, р. 695.

  45. Uchiya, K., Takahashi, H., Yagi, T., et al., Comparative genome analysis of Mycobacterium avium revealed genetic diversity in strains that cause pulmonary and disseminated disease, PLoS One, 2013, vol. 8, no. 8, p. e71831.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Xu, G., Li, Y., Yang, J., et al., Mycobacterium bovis Mce4E protein may play a role in modulating cytokine expression profile in alveolar macrophage, Int. J. Tuberc. Lung Dis., 2008, vol. 12, pp. 664–669.

    CAS  PubMed  Google Scholar 

  47. Zhang, F. and Xie, J.P., Mammalian cell entry gene family of Mycobacterium tuberculosis,Mol. Cell Biochem., 2011, vol. 352, nos. 1–2, pp. 1–10.

    Article  CAS  PubMed  Google Scholar 

  48. Zhang, Y., Li, J., Li, B., et al., Mycobacterium tuberculosis Mce3C promotes mycobacteria entry into macrophages through activation of β2 integrin-mediated signaling pathway, Cell Microbiol., 2018, vol. 20, no. 2. https://doi.org/10.1111/cmi.12800

Download references

Author information

Authors and Affiliations

  1. Vavilov Institute of General Genetics, Russian Academy of Sciences, 117971, Moscow, Russia

    M. V. Zaychikova & V. N. Danilenko

Authors
  1. M. V. Zaychikova
    View author publications

    Search author on:PubMed Google Scholar

  2. V. N. Danilenko
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to M. V. Zaychikova.

Ethics declarations

FUNDING

This work was supported by a grant from the Russian National Fund, project no. 17-75-20060 “Search for biotargets of potential anti-tuberculosis drugs of the azolo[1,2,4,5]tetrazine class” (2017–2019).

COMPLIANCE WITH ETHICAL STANDARDS

Conflict of interests. The authors declare that they have no conflicts of interest.

Statement on the welfare of humans or animals. This article does not contain any studies involving animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zaychikova, M.V., Danilenko, V.N. The Actinobacterial mce Operon: Structure and Functions. Biol Bull Rev 10, 520–525 (2020). https://doi.org/10.1134/S2079086420060079

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1134/S2079086420060079

Keywords: