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

Pierre Lapaquette1,2, Sabrina Fritah1,2, Nouara Lhocine3,4

  • 1Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France.

Elife
|December 13, 2017
PubMed

Insights

Shigella flexneri infection inhibits host cell sumoylation by cleaving the SUMO E1 enzyme, SAE2. This process, mediated by calcium and calpains, facilitates bacterial invasion by altering RhoGDIα sumoylation and actin dynamics.

Area of Science:

  • Cellular Biology
  • Microbiology
  • Biochemistry

Background:

  • Disruption of sumoylation/desumoylation balance is linked to diseases like cancer and infections.
  • Mechanisms controlling global SUMO homeostasis are not fully understood.

Purpose of the Study:

  • To investigate how *Shigella flexneri* infection affects host cell sumoylation.
  • To elucidate the molecular mechanisms underlying SUMO balance disruption during infection.
  • To explore the role of SUMOylation in regulating bacterial invasion.

Main Methods:

  • In vitro and in vivo infection models using *Shigella flexneri*.
  • Analysis of SUMO E1 enzyme (SAE2) cleavage and activity.
  • Investigation of RhoGDIα sumoylation status and its impact on RhoGTPase activity.
  • Assessment of actin polymerization and cytoskeletal rearrangements.

Main Results:

  • *Shigella flexneri* infection inhibits host sumoylation in epithelial cells.
  • Calcium/calpain-dependent cleavage of SAE2 is the primary mechanism for sumoylation inhibition.
  • Altered RhoGDIα sumoylation by *Shigella* promotes bacterial invasion.
  • SUMO modification restrains bacterial entry by limiting effector-induced cytoskeletal changes.

Conclusions:

  • *Shigella* infection actively suppresses host sumoylation via calcium-activated calpains targeting SAE2.
  • This suppression facilitates bacterial invasion by modulating RhoGDIα and actin dynamics.
  • Calcium-activated calpains are key regulators of cellular sumoylation with broad pathological implications.

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