The Mycobacterium tuberculosis Phagosome

  • Esteban A. Roberts
  • Vojo Deretic
Part of the Methods in Molecular Biology™ book series (MIMB, volume 445)

Summary

Tuberculosis is currently the most devastating human bacterial disease, causing millions of deaths annually and infecting an overwhelming percentage of the global population. Its success as a scourge lies in the ability of Mycobacterium tuberculosis to prevent normal phagolysosome biogenesis, essential to the destruction of invading microorganisms, inside macrophages. Recent work has identified host GTPases involved in the block of normal phagolysosome biogenesis during mycobacterial infection and has provided a set of methods, in particular efficient macrophage transfection, which will prove essential in examining the role of host effectors in this process.

Key Words

M. tuberculosis phagosome Rabs maturation Rab conversion 

References

  1. 1.
    Russell, D. G., Mwandumba, H. C., and Rhoades. E. E. (2002) Mycobacterium and the coat of many lipids. J. Cell Biol. 158, 421.CrossRefPubMedGoogle Scholar
  2. 2.
    Via, L. E., Deretic, D., Ulmer, R. J., Hibler, N. S., Huber, L. A., and Deretic, V. (1997) Arrest of mycobacterial phagosome maturation is caused by a block in vesicle fusion between stages controlled by rab5 and rab7. J. Biol. Chem. 272, 13326.CrossRefPubMedGoogle Scholar
  3. 3.
    Sturgill-Koszycki, S., Schaible, U. E., and Russell, D. G. (1996) Mycobacterium-containing phagosomes are accessible to early endosomes and reflect a transitional state in normal phagosome biogenesis. EMBO J. 15, 6960.Google Scholar
  4. 4.
    Clemens, D. L., and Horwitz, M. A. (1996) The Mycobacterium tuberculosis phagosome interacts with early endosomes and is accessible to exogenously administered transferrin. J. Exp. Med. 184, 1349.CrossRefPubMedGoogle Scholar
  5. 5.
    Pereira-Leal, J. B., and Seabra, M. C. (2001) Evolution of the Rab family of small GTP-binding proteins. J. Mol. Biol. 313, 889.CrossRefPubMedGoogle Scholar
  6. 6.
    Pfeffer, S. R. (2005) Structural clues to Rab GTPase functional diversity. J. Biol. Chem. 280, 15485.CrossRefPubMedGoogle Scholar
  7. 7.
    Fratti, R. A., Backer, J. M., Gruenberg, J., Corvera, S., and Deretic, V. (2001) Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest. J. Cell Biol. 154, 631.CrossRefPubMedGoogle Scholar
  8. 8.
    Kelley, V. A. and Schorey, J. S. (2003) Mycobacterium’s arrest of phagosome maturation in macrophages requires Rab5 activity and accessibility to iron. Mol. Biol. Cell 14, 3366.Google Scholar
  9. 9.
    Clemens, D. L., Lee, B. Y., and Horwitz, M. A. (2000) Mycobacterium tuberculosis and Legionella pneumophila phagosomes exhibit arrested maturation despite acquisition of Rab7. Infect. Immun. 68, 5154.Google Scholar
  10. 10.
    Clemens, D. L., Lee, B. Y., and Horwitz, M. A.. (2000) Deviant expression of Rab5 on phagosomes containing the intracellular pathogens Mycobacterium tuberculosis and Legionella pneumophila is associated with altered phagosomal fate. Infect. Immun. 68, 2671.Google Scholar
  11. 11.
    Rink, J., Ghigo, E., Kalaidzidis, Y., and Zerial, M. (2005) Rab conversion as a mechanism of progression from early to late endosomes. Cell 122, 735.CrossRefPubMedGoogle Scholar
  12. 12.
    Deretic, V. (2005) Ay, there’s the Rab: organelle maturation by Rab conversion. Dev. Cell 9, 446.CrossRefPubMedGoogle Scholar
  13. 13.
    Roberts, E. A., Chua, J., Kyei, G. B., and Deretic, V. (2006) Higher order Rab programming in phagolysosome biogenesis. J. Cell Biol. 174, 923.CrossRefPubMedGoogle Scholar
  14. 14.
    Kyei, G. B., Vergne, I., Chua, J., et al. (2006) Rab14 is critical for maintenance of Mycobacterium tuberculosis phagosome maturation arrest. EMBO J. 25, 5250.Google Scholar
  15. 15.
    Escher, G., Hoang, A., Georges, S., et al. (2005) Demethylation using the epigenetic modifier, 5-azacytidine, increases the efficiency of transient transfection of macrophages. J. Lipid Res. 46, 356.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Esteban A. Roberts
    • 1
  • Vojo Deretic
    • 2
  1. 1.Department of Molecular Genetics and MicrobiologyUniversity of New Mexico School of MedicineAlbuquerque
  2. 2.Health Sciences Center, Department Molecular Genetics and MicrobiologyUniversity of New Mexico Health Sciences CenterAlbuquerqueUSA

Personalised recommendations