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Imaging Ca2+ Responses During Shigella Infection of Epithelial Cells
Published on: May 24, 2018
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.
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 RhoGDIα, 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.
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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