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Modulation of phagosome biogenesis by Legionella pneumophila creates an organelle permissive for intracellular growth

Nature Cell Biology volume 1, pages 451–453 (1999)Cite this article

Fundamental to the pathogenic lifestyle of several intracellular bacteria is their ability to modulate trafficking of the phagosomes in which they reside1. The bacterial pathogen Legionella pneumophila resides in a phagosome that restricts its fusion with host endosomes and lysosomes2. The intracellular fate of L. pneumophila is determined by a type-IV-related transport system encoded by 24 dot and icm virulence genes3,4. L. pneumophila dot and icm mutants reside in phagosomes that rapidly fuse with lysosomes, resulting in decreased intracellular survival and a severe intracellular growth defect5,6. Here we show that the primary function of the dot and icm products is to transmit a functionally cis-acting signal to the host macrophage that drives maturation of the L. pneumophila phagosome into a replicative vacuole. We find that L. pneumophila dot and icm mutants are able to grow intracellularly when the bacteria are residing in a phagosome established by L. pneumophila that retains its ability to alter phagosome trafficking. These results show that L. pneumophila tailors the phagosome into a specialized organelle permissive for bacterial growth through the specific actions of the dot/icm genes.

To further address whether there is a signal transmitted by virulent L. pneumophila that has the capacity to act in trans, we used a mixed inoculum consisting of a wild-type and a dotA mutant strain of L. pneumophila to infect bone-marrow-derived macrophages. If the wild-type bacteria were secreting a trans-acting factor, it could potentially restore intracellular growth to a dotA mutant that has lost the ability to alter phagosome trafficking. In these studies, we used a dotA mutant carrying a plasmid that produces green fluorescent protein (GFP). In macrophages that had ingested both wild-type and mutant bacteria, we did not detect replication of dotA mutants in phagosomes that were isolated from those containing wild-type L. pneumophila (Fig. 1b).

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Figure 1: L. pneumophila create an organelle permissive for intracellular replication by altering trafficking of the phagosome in which they reside, but do not affect trafficking of heterologous vacuoles.
Figure 2: Early signalling events mediated by the dot/icm gene products are sufficient to create a vacuole that supports intracellular multiplication of L. pneumophila.

References

  1. Sinai, A. P. & Joiner, K. A. Annu. Rev. Microbiol. 51, 415–462 (1997).

    Article  CAS  Google Scholar 

  2. Horwitz, M. A. J. Exp. Med. 158, 2108–2126 (1983).

    Article  CAS  Google Scholar 

  3. Vogel, J. P., Andrews, H. L., Wong, S. K. & Isberg, R. R. Science 279, 873–876 ( 1998).

    Article  CAS  Google Scholar 

  4. Segal, G., Purcell, M. & Shuman, H. A. Proc. Natl Acad. Sci. USA 95, 1669–1674 (1998).

    Article  CAS  Google Scholar 

  5. Wiater, L. A., Dunn, K., Maxfield, F. R. & Shuman, H. A. Infect. Immun. 66, 4450–4460 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Roy, C. R., Berger, K. & Isberg, R. R. Mol. Microbiol. 28, 663– 674 (1998).

    Article  CAS  Google Scholar 

  7. Mintz, C. S., Chen, J. & Shuman, H. Infect. Immun. 56, 1449– 1455 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Uchiya, K. et al. EMBO J. 18, 3924–3933 (1999).

    Article  CAS  Google Scholar 

  9. Abu Kwaik, Y., Gao, L. Y., Stone, B. J., Venkataraman, C. & Harb, O. S. Appl Environ. Microbiol. 64, 3127–3133 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Horwitz, M. A. J. Exp. Med. 158, 1319–1331 (1983).

    Article  CAS  Google Scholar 

  11. Swanson, M. S. & Isberg, R. R. Infect. Immun. 63, 3609–3620 ( 1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Andrews, H. L., Vogel, J. P. & Isberg, R. R. Infect. Immun. 66, 950– 958 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Zuckman, D. M., Hung, J. B. & Roy, C. R. Mol. Microbiol. 32, 990– 1001 (1999).

    Article  CAS  Google Scholar 

  14. Cormack, B. P., Valdivia, R. H. & Falkow, S. Gene 173, 33– 38 (1996).

    Article  CAS  Google Scholar 

  15. Morales, V. M., Backman, A. & Bagdasarian, M. Gene 97, 39– 47 (1991).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank A. Marra for constructing and providing pAM239; H. Andrews for HL056; and J. Galán and N. Andrews for helpful suggestions during the preparation of this manuscript. This work was funded by NIH grant AI41699.

Correspondence and requests for materials should be addressed to C.R.R.

Supplementary information is available on Nature Cell Biology’s World-Wide Web site (http://cellbio.nature.com ) or as paper copy from the London editorial office of Nature Cell Biology.

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  1. Jörn Coers and Catherine Monahan: These authors contributed equally to this work

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  1. Yale University School of Medicine, Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Room 354, 295 Congress Avenue, New Haven, 06511, Connecticut, USA

    Jörn Coers, Catherine Monahan & Craig R. Roy

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  1. Jörn Coers
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Correspondence to Craig R. Roy.

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Coers, J., Monahan, C. & Roy, C. Modulation of phagosome biogenesis by Legionella pneumophila creates an organelle permissive for intracellular growth. Nat Cell Biol 1, 451–453 (1999). https://doi.org/10.1038/15687

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