Shigella entry unveils a calcium/calpain-dependent mechanism for inhibiting sumoylation

Abstract

Disruption of the sumoylation/desumoylation equilibrium is associated with several disease states such as cancer and infections, however the mechanisms regulating the global SUMO balance remain poorly defined. Here, we show that infection by Shigella flexneri, the causative agent of human bacillary dysentery, switches off host sumoylation during epithelial cell infection in vitro and in vivo and that this effect is mainly mediated by a calcium/calpain-induced cleavage of the SUMO E1 enzyme SAE2, thus leading to sumoylation inhibition. Furthermore, we describe a mechanism by which Shigella promotes its own invasion by altering the sumoylation state of RhoGDIa, a master negative regulator of RhoGTPase activity and actin polymerization. Together, our data suggest that SUMO modification is essential to restrain pathogenic bacterial entry by limiting cytoskeletal rearrangement induced by bacterial effectors. Moreover, these findings identify calcium-activated calpains as powerful modulators of cellular sumoylation levels with potentially broad implications in several physiological and pathological situations.

Article and author information

Author details

  1. Pierre Lapaquette

    Nuclear Organization and Oncogenesis, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Sabrina Fritah

    Nuclear Organization and Oncogenesis, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Nouara Lhocine

    Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexandra Andrieux

    Nuclear Organization and Oncogenesis, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Giulia Nigro

    Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Joëlle Mounier

    Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Philippe Sansonetti

    Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Anne Dejean

    Nuclear Organization and Oncogenesis, Institut Pasteur, Paris, France
    For correspondence
    anne.dejean@pasteur.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4778-6840

Funding

Ligue Contre le Cancer (Post-doc fellowship to P. Lapaquette and labelled team to A. Dejean)

  • Pierre Lapaquette
  • Anne Dejean

Institut Pasteur

  • Philippe Sansonetti
  • Anne Dejean

Institut National Du Cancer

  • Anne Dejean

H2020 European Research Council (SUMOSTRESS)

  • Anne Dejean

Sidaction

  • Sabrina Fritah

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal experiments were performed accordingly to the guidelines of the Institut Pasteur's ethical committee for animal use in research (CETEA number 2013-0028).

Reviewing Editor

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Publication history

  1. Received: April 6, 2017
  2. Accepted: December 11, 2017
  3. Accepted Manuscript published: December 12, 2017 (version 1)
  4. Accepted Manuscript updated: December 13, 2017 (version 2)
  5. Accepted Manuscript updated: December 14, 2017 (version 3)
  6. Version of Record published: December 27, 2017 (version 4)

Copyright

© 2017, Lapaquette et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Pierre Lapaquette
  2. Sabrina Fritah
  3. Nouara Lhocine
  4. Alexandra Andrieux
  5. Giulia Nigro
  6. Joëlle Mounier
  7. Philippe Sansonetti
  8. Anne Dejean
(2017)
Shigella entry unveils a calcium/calpain-dependent mechanism for inhibiting sumoylation
eLife 6:e27444.
https://doi.org/10.7554/eLife.27444

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