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Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis

Nature volume 455, pages 1114–1118 (2008)Cite this article

Abstract

The ability to cross host barriers is an essential virulence determinant of invasive microbial pathogens. Listeria monocytogenes is a model microorganism that crosses human intestinal and placental barriers, and causes severe maternofetal infections by an unknown mechanism1. Several studies have helped to characterize the bacterial invasion proteins InlA and InlB2. However, their respective species specificity has complicated investigations on their in vivo role3,4. Here we describe two novel and complementary animal models for human listeriosis: the gerbil, a natural host for L. monocytogenes, and a knock-in mouse line ubiquitously expressing humanized E-cadherin. Using these two models, we uncover the essential and interdependent roles of InlA and InlB in fetoplacental listeriosis, and thereby decipher the molecular mechanism underlying the ability of a microbe to target and cross the placental barrier.

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Figure 1: InlA and InlB internalization pathways in gerbils.
Figure 2: In vivo real-time imaging of fetoplacental listeriosis in gerbils.
Figure 3: Interdependent roles of InlA and InlB in placental invasion and fetal infection in gerbils.
Figure 4: Infection of primary epithelial cells and mice expressing a humanized mEcad able to interact with InlA.

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Data deposits

The Gerbil Ecad and Gerbil Met nucleotide sequences are deposited in GenBank under accession numbers EU878370 and EU878371, respectively.

References

  1. Mylonakis, E., Paliou, M., Hohmann, E. L., Calderwood, S. B. & Wing, E. J. Listeriosis during pregnancy: a case series and review of 222 cases. Medicine (Baltimore) 81, 260–269 (2002)

    Article  Google Scholar 

  2. Hamon, M., Bierne, H. & Cossart, P. Listeria monocytogenes: a multifaceted model. Nature Rev. Microbiol. 4, 423–434 (2006)

    Article  CAS  Google Scholar 

  3. Lecuit, M. et al. A single amino acid in E-cadherin responsible for host specificity towards the human pathogen Listeria monocytogenes . EMBO J. 18, 3956–3963 (1999)

    Article  CAS  Google Scholar 

  4. Khelef, N., Lecuit, M., Bierne, H. & Cossart, P. Species specificity of the Listeria monocytogenes InlB protein. Cell. Microbiol. 8, 457–470 (2006)

    Article  CAS  Google Scholar 

  5. Lecuit, M. Human listeriosis and animal models. Microbes Infect. 9, 1216–1225 (2007)

    Article  CAS  Google Scholar 

  6. Abram, M. et al. Murine model of pregnancy-associated Listeria monocytogenes infection. FEMS Immunol. Med. Microbiol. 35, 177–182 (2003)

    Article  CAS  Google Scholar 

  7. Cossart, P., Pizarro-Cerda, J. & Lecuit, M. Invasion of mammalian cells by Listeria monocytogenes: functional mimicry to subvert cellular functions. Trends Cell Biol. 13, 23–31 (2003)

    Article  CAS  Google Scholar 

  8. Pizarro-Cerda, J. & Cossart, P. Bacterial adhesion and entry into host cells. Cell 124, 715–727 (2006)

    Article  CAS  Google Scholar 

  9. Mengaud, J., Ohayon, H., Gounon, P., Mege, R. M. & Cossart, P. E-cadherin is the receptor for internalin, a surface protein required for entry of L. monocytogenes into epithelial cells. Cell 84, 923–932 (1996)

    Article  CAS  Google Scholar 

  10. Shen, Y., Naujokas, M., Park, M. & Ireton, K. InIB-dependent internalization of Listeria is mediated by the Met receptor tyrosine kinase. Cell 103, 501–510 (2000)

    Article  CAS  Google Scholar 

  11. Braun, L., Ghebrehiwet, B. & Cossart, P. gC1q-R/p32, a C1q-binding protein, is a receptor for the InlB invasion protein of Listeria monocytogenes . EMBO J. 19, 1458–1466 (2000)

    Article  CAS  Google Scholar 

  12. Jonquieres, R., Pizarro-Cerda, J. & Cossart, P. Synergy between the N- and C-terminal domains of InlB for efficient invasion of non-phagocytic cells by Listeria monocytogenes . Mol. Microbiol. 42, 955–965 (2001)

    Article  CAS  Google Scholar 

  13. Lecuit, M. et al. A transgenic model for listeriosis: role of internalin in crossing the intestinal barrier. Science 292, 1722–1725 (2001)

    Article  ADS  CAS  Google Scholar 

  14. Jacquet, C. et al. A molecular marker for evaluating the pathogenic potential of foodborne Listeria monocytogenes . J. Infect. Dis. 189, 2094–2100 (2004)

    Article  CAS  Google Scholar 

  15. Lecuit, M. et al. Targeting and crossing of the human maternofetal barrier by Listeria monocytogenes: role of internalin interaction with trophoblast E-cadherin. Proc. Natl Acad. Sci. USA 101, 6152–6157 (2004)

    Article  ADS  CAS  Google Scholar 

  16. Bakardjiev, A. I., Stacy, B. A., Fisher, S. J. & Portnoy, D. A. Listeriosis in the pregnant guinea pig: a model of vertical transmission. Infect. Immun. 72, 489–497 (2004)

    Article  CAS  Google Scholar 

  17. Le Monnier, A. et al. ActA is required for crossing of the fetoplacental barrier by Listeria monocytogenes . Infect. Immun. 75, 950–957 (2007)

    Article  CAS  Google Scholar 

  18. Pirie, J. H. H. A new disease of veld rodents. ‘Tiger river disease’. Publ. S. Afr. Inst. Med. Res. 3, 163–186 (1927)

    Google Scholar 

  19. Schubert, W. D. et al. Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin. Cell 111, 825–836 (2002)

    Article  CAS  Google Scholar 

  20. Niemann, H. H. et al. Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB. Cell 130, 235–246 (2007)

    Article  CAS  Google Scholar 

  21. Lecuit, M. & Cossart, P. Genetically-modified-animal models for human infections: the Listeria paradigm. Trends Mol. Med. 8, 537–542 (2002)

    Article  CAS  Google Scholar 

  22. Glaser, P. et al. Comparative genomics of Listeria species. Science 294, 849–852 (2001)

    ADS  CAS  PubMed  Google Scholar 

  23. Vazquez-Boland, J. A. et al. Listeria pathogenesis and molecular virulence determinants. Clin. Microbiol. Rev. 14, 584–640 (2001)

    Article  CAS  Google Scholar 

  24. Lecuit, M., Ohayon, H., Braun, L., Mengaud, J. & Cossart, P. Internalin of Listeria monocytogenes with an intact leucine-rich repeat region is sufficient to promote internalization. Infect. Immun. 65, 5309–5319 (1997)

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Braun, L., Ohayon, H. & Cossart, P. The InIB protein of Listeria monocytogenes is sufficient to promote entry into mammalian cells. Mol. Microbiol. 27, 1077–1087 (1998)

    Article  CAS  Google Scholar 

  26. Rubin, L. L. et al. A cell culture model of the blood–brain barrier. J. Cell Biol. 115, 1725–1735 (1991)

    Article  CAS  Google Scholar 

  27. Bierne, H. & Cossart, P. InlB, a surface protein of Listeria monocytogenes that behaves as an invasin and a growth factor. J. Cell Sci. 115, 3357–3367 (2002)

    CAS  PubMed  Google Scholar 

  28. Athman, R. et al. Shigella flexneri infection is dependent on villin in the mouse intestine and in primary cultures of intestinal epithelial cells. Cell. Microbiol. 7, 1109–1116 (2005)

    Article  CAS  Google Scholar 

  29. Dramsi, S., Levi, S., Triller, A. & Cossart, P. Entry of Listeria monocytogenes into neurons occurs by cell-to-cell spread: an in vitro study. Infect. Immun. 66, 4461–4468 (1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Perez-Garcia, C. C. et al. A simple procedure to perform intravenous injections in the Mongolian gerbil (Meriones unguiculatus). Lab. Anim. 37, 68–71 (2003)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This paper is dedicated to the memory of Charles Babinet, our friend and colleague, who died a few days before the submission of this manuscript. We thank his collaborators S. Vandormael-Pournin, C. Kress and M. Cohen-Tannoudji, as well as L. Larue and S. Tajbakhsh for help in generating the knock-in mice. We thank C. Hill for the gift of the pPL2lux-P hlyA plasmid, M.-A. Nahori for help with animal experiments, P. Roux for help with confocal imaging, P.-M. Lledo and M. Gabellec for help with vibratome sectioning, V. Masse for help with statistical analysis and O. Lortholary for his support. We also thank S. Mostowy for reading the paper. This work received financial support from the Institut Pasteur, Inserm and INRA. O. Disson received financial support from the Fondation pour la Recherche Médicale (FRM) and Inserm, P.C. is an Howard Hughes Medical Institute international research scholar and M.L. is a recipient of an Inserm interface contract.

Author Contributions M.L. planned the project and analysed the experiments, together with P.C., as well as O. Disson, S.G., E.H. and G.N. O. Disson, S.G., E.H. and G.N. performed the experiments. Engineering of knock-in mice was done with F.L.-V. and C.B. O. Dussurget was involved in bioluminescence imaging; M.R. and A.L.M. were involved in the epidemiological study. M.L. wrote the manuscript and all co-authors commented on it.

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Author notes

  1. Olivier Disson, Solène Grayo and Eugénie Huillet: These authors contributed equally to this work.

  2. Charles Babinet: Deceased.

Authors and Affiliations

  1. Institut Pasteur, Groupe Microorganismes et Barrières de l’Hôte, Unité des Interactions Bactéries-Cellules, F-75015 Paris, France

    Olivier Disson, Solène Grayo, Georgios Nikitas & Marc Lecuit

  2. Inserm Avenir U604, F-75015 Paris, France

    Olivier Disson, Solène Grayo, Georgios Nikitas & Marc Lecuit

  3. Institut Pasteur, Centre National de Référence des Listeria, F-75015 Paris, France

    Solène Grayo, Marie Ragon, Alban Le Monnier & Marc Lecuit

  4. Institut Pasteur, Unité des Interactions Bactéries-Cellules, F-75015 Paris, France

    Eugénie Huillet, Olivier Dussurget & Pascale Cossart

  5. Inserm U604, F-75015 Paris, France

    Eugénie Huillet, Olivier Dussurget & Pascale Cossart

  6. INRA USC2020, F-75015 Paris, France

    Eugénie Huillet, Olivier Dussurget & Pascale Cossart

  7. Institut Pasteur, Centre d’Ingénierie Génétique Murine, F-75015 Paris, France

    Francina Langa-Vives

  8. Institut Pasteur, Unité de Biologie du Développement, F-75015 Paris, France

    Charles Babinet

  9. Centre d’Infectiologie Necker-Pasteur, Service des Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, F-75015 Paris, France

    Marc Lecuit

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  1. Olivier Disson
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Corresponding author

Correspondence to Marc Lecuit.

Supplementary information

Supplementary Information

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Disson, O., Grayo, S., Huillet, E. et al. Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis. Nature 455, 1114–1118 (2008). https://doi.org/10.1038/nature07303

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