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Listeria monocytogenes impairs SUMOylation for efficient infection

An Author Correction to this article was published on 16 April 2020


During infection, pathogenic bacteria manipulate the host cell in various ways to allow their own replication, propagation and escape from host immune responses. Post-translational modifications are unique mechanisms that allow cells to rapidly, locally and specifically modify activity or interactions of key proteins. Some of these modifications, including phosphorylation and ubiquitylation1,2, can be induced by pathogens. However, the effects of pathogenic bacteria on SUMOylation, an essential post-translational modification in eukaryotic cells3, remain largely unknown. Here we show that infection with Listeria monocytogenes leads to a decrease in the levels of cellular SUMO-conjugated proteins. This event is triggered by the bacterial virulence factor listeriolysin O (LLO), which induces a proteasome-independent degradation of Ubc9, an essential enzyme of the SUMOylation machinery, and a proteasome-dependent degradation of some SUMOylated proteins. The effect of LLO on Ubc9 is dependent on the pore-forming capacity of the toxin and is shared by other bacterial pore-forming toxins like perfringolysin O (PFO) and pneumolysin (PLY). Ubc9 degradation was also observed in vivo in infected mice. Furthermore, we show that SUMO overexpression impairs bacterial infection. Together, our results reveal that Listeria, and probably other pathogens, dampen the host response by decreasing the SUMOylation level of proteins critical for infection.

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Figure 1: Decrease in SUMO-conjugated proteins upon infection with Listeria.
Figure 2: L. monocytogenes induces a specific degradation of Ubc9.
Figure 3: Characterization of LLO-mediated Ubc9 degradation.
Figure 4: Roles of SUMOylation in Listeria infection.


  1. Hamon, M. A. & Cossart, P. Histone modifications and chromatin remodeling during bacterial infections. Cell Host Microbe 4, 100–109 (2008)

    Article  CAS  Google Scholar 

  2. Rytkonen, A. & Holden, D. W. Bacterial interference of ubiquitination and deubiquitination. Cell Host Microbe 1, 13–22 (2007)

    Article  CAS  Google Scholar 

  3. Geiss-Friedlander, R. & Melchior, F. Concepts in sumoylation: a decade on. Nature Rev. Mol. Cell Biol. 8, 947–956 (2007)

    Article  CAS  Google Scholar 

  4. Cossart, P. & Toledo-Arana, A. Listeria monocytogenes, a unique model in infection biology: an overview. Microbes Infect. 10, 1041–1050 (2008)

    Article  CAS  Google Scholar 

  5. Veiga, E. & Cossart, P. Listeria hijacks the clathrin-dependent endocytic machinery to invade mammalian cells. Nature Cell Biol. 7, 894–900 (2005)

    Article  CAS  Google Scholar 

  6. Bonazzi, M., Veiga, E., Cerda, J. P. & Cossart, P. Successive post-translational modifications of E-cadherin are required for InlA-mediated internalisation of Listeria monocytogenes. Cell. Microbiol. 10, 2208–2222 (2008)

    Article  CAS  Google Scholar 

  7. Hamon, M. A. et al. Histone modifications induced by a family of bacterial toxins. Proc. Natl Acad. Sci. USA 104, 13467–13472 (2007)

    Article  ADS  CAS  Google Scholar 

  8. Vertegaal, A. C. et al. Distinct and overlapping sets of SUMO-1 and SUMO-2 target proteins revealed by quantitative proteomics. Mol. Cell. Proteomics 5, 2298–2310 (2006)

    Article  CAS  Google Scholar 

  9. Hochstrasser, M. Origin and function of ubiquitin-like proteins. Nature 458, 422–429 (2009)

    Article  ADS  CAS  Google Scholar 

  10. Nacerddine, K. et al. The SUMO pathway is essential for nuclear integrity and chromosome segregation in mice. Dev. Cell 9, 769–779 (2005)

    Article  CAS  Google Scholar 

  11. Hay, R. T. SUMO-specific proteases: a twist in the tail. Trends Cell Biol. 17, 370–376 (2007)

    Article  CAS  Google Scholar 

  12. Zhao, J. Sumoylation regulates diverse biological processes. Cell. Mol. Life Sci. 64, 3017–3033 (2007)

    Article  CAS  Google Scholar 

  13. Boggio, R. & Chiocca, S. Viruses and sumoylation: recent highlights. Curr. Opin. Microbiol. 9, 430–436 (2006)

    Article  CAS  Google Scholar 

  14. Gevaert, K. et al. Stable isotopic labeling in proteomics. Proteomics 8, 4873–4885 (2008)

    Article  CAS  Google Scholar 

  15. Saitoh, H. & Hinchey, J. Functional heterogeneity of small ubiquitin-related protein modifiers SUMO-1 versus SUMO-2/3. J. Biol. Chem. 275, 6252–6258 (2000)

    Article  CAS  Google Scholar 

  16. Golebiowski, F. et al. System-wide changes to SUMO modifications in response to heat shock. Sci. Signal. 2, ra24 (2009)

    Article  Google Scholar 

  17. Schnupf, P. & Portnoy, D. A. Listeriolysin O: a phagosome-specific lysin. Microbes Infect. 9, 1176–1187 (2007)

    Article  CAS  Google Scholar 

  18. Matunis, M. J., Coutavas, E. & Blobel, G. A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex. J. Cell Biol. 135, 1457–1470 (1996)

    Article  CAS  Google Scholar 

  19. Nato, F. et al. Production and characterization of neutralizing and nonneutralizing monoclonal antibodies against listeriolysin O. Infect. Immun. 59, 4641–4646 (1991)

    Article  CAS  Google Scholar 

  20. Michel, E., Reich, K. A., Favier, R., Berche, P. & Cossart, P. Attenuated mutants of the intracellular bacterium Listeria monocytogenes obtained by single amino acid substitutions in listeriolysin O. Mol. Microbiol. 4, 2167–2178 (1990)

    Article  CAS  Google Scholar 

  21. Hotze, E. M. et al. Monomer-monomer interactions drive the prepore to pore conversion of a beta-barrel-forming cholesterol-dependent cytolysin. J. Biol. Chem. 277, 11597–11605 (2002)

    Article  CAS  Google Scholar 

  22. Boggio, R., Colombo, R., Hay, R. T., Draetta, G. F. & Chiocca, S. A mechanism for inhibiting the SUMO pathway. Mol. Cell 16, 549–561 (2004)

    Article  CAS  Google Scholar 

  23. Boggio, R., Passafaro, A. & Chiocca, S. Targeting SUMO E1 to ubiquitin ligases: a viral strategy to counteract sumoylation. J. Biol. Chem. 282, 15376–15382 (2007)

    Article  CAS  Google Scholar 

  24. Dramsi, S. & Cossart, P. Listeriolysin O-mediated calcium influx potentiates entry of Listeria monocytogenes into the human Hep-2 epithelial cell line. Infect. Immun. 71, 3614–3618 (2003)

    Article  CAS  Google Scholar 

  25. Tang, P., Rosenshine, I., Cossart, P. & Finlay, B. B. Listeriolysin O activates mitogen-activated protein kinase in eucaryotic cells. Infect. Immun. 64, 2359–2361 (1996)

    Article  CAS  Google Scholar 

  26. Lin, X., Liang, M., Liang, Y. Y., Brunicardi, F. C. & Feng, X. H. SUMO-1/Ubc9 promotes nuclear accumulation and metabolic stability of tumor suppressor Smad4. J. Biol. Chem. 278, 31043–31048 (2003)

    Article  CAS  Google Scholar 

  27. Kang, J. S., Saunier, E. F., Akhurst, R. J. & Derynck, R. The type I TGF-beta receptor is covalently modified and regulated by sumoylation. Nature Cell Biol. 10, 654–664 (2008)

    Article  CAS  Google Scholar 

  28. Fitzpatrick, D. R. & Bielefeldt-Ohmann, H. Transforming growth factor beta in infectious disease: always there for the host and the pathogen. Trends Microbiol. 7, 232–236 (1999)

    Article  CAS  Google Scholar 

  29. Nakane, A. et al. Transforming growth factor beta is protective in host resistance against Listeria monocytogenes infection in mice. Infect. Immun. 64, 3901–3904 (1996)

    Article  CAS  Google Scholar 

  30. Glomski, I. J., Gedde, M. M., Tsang, A. W., Swanson, J. A. & Portnoy, D. A. The Listeria monocytogenes hemolysin has an acidic pH optimum to compartmentalize activity and prevent damage to infected host cells. J. Cell Biol. 156, 1029–1038 (2002)

    Article  CAS  Google Scholar 

  31. Dramsi, S. et al. Entry of Listeria monocytogenes into hepatocytes requires expression of inIB, a surface protein of the internalin multigene family. Mol. Microbiol. 16, 251–261 (1995)

    Article  CAS  Google Scholar 

  32. Bischof, O. et al. The E3 SUMO ligase PIASy is a regulator of cellular senescence and apoptosis. Mol. Cell 22, 783–794 (2006)

    Article  CAS  Google Scholar 

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We thank V. Villiers for technical assistance. Work in the P.C. laboratory received financial support from Institut Pasteur, INSERM, INRA and European Research Council (ERC, Advanced Grant 233348). We further acknowledge support by research grants from the Fund for Scientific Research – Flanders (Belgium) (project number G.0042.07), the Concerted Research Actions (project BOF07/GOA/012) from Ghent University and the Inter University Attraction Poles (IUAP06). D.R. is supported by a fellowship from the Association pour la Recherche sur le Cancer, F.I. is a Research Assistant of the Research Foundation – Flanders (Fonds Wetenschappelijk Onderzoek – Vlaanderen) and P.C. is an international research scholar of the Howard Hughes Medical Institute.

Author Contributions P.C. planned the project. D.R., K.G., J.V., A.D. and P.C. designed the research, D.R., M.H., E.G., M.-A.N., F.I. and H. N.-K. performed the experiments. D.R., M.H., K.G., J.V. and P.C. analysed the experiments. D.R. and P.C. wrote the paper and co-authors commented on it.

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Correspondence to Pascale Cossart.

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Ribet, D., Hamon, M., Gouin, E. et al. Listeria monocytogenes impairs SUMOylation for efficient infection. Nature 464, 1192–1195 (2010).

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