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PtdIns5P activates the host cell PI3-kinase/Akt pathway during Shigella flexneri infection

Caroline Pendaries1, Hélène Tronchère, Laurence Arbibe

  • 1INSERM Unité 563, CPTP, Département d'Oncogenèse et Signalisation dans les Cellules Hématopoiétiques, Hôpital Purpan, Toulouse, France.

The EMBO Journal
|February 17, 2006
PubMed

Insights

Shigella flexneri uses the IpgD virulence factor to produce phosphatidylinositol 5 monophosphate (PtdIns5P), activating host cell Akt signaling. This bacterial mechanism reveals a new pathway for PI 3-kinase/Akt activation crucial for host cell survival.

Area of Science:

  • Microbiology
  • Cell Biology
  • Biochemistry

Background:

  • Shigella flexneri is an invasive bacterial pathogen that utilizes type III secretion systems to deliver virulence factors into host cells.
  • Phosphoinositides are key regulators of cellular processes, including membrane trafficking and signaling pathways.

Purpose of the Study:

  • To investigate the role of the Shigella virulence factor IpgD in host cell signaling.
  • To elucidate the mechanism by which IpgD affects host cell Akt phosphorylation and survival.

Main Methods:

  • Characterization of IpgD's enzymatic activity as a phosphoinositide 4-phosphatase.
  • Analysis of PtdIns5P production and localization during S. flexneri infection.
  • Assessment of Akt phosphorylation in response to IpgD expression or PtdIns5P addition/sequestration.
  • Investigation of PI 3-kinase activation by IpgD and PtdIns5P.

Main Results:

  • IpgD generates phosphatidylinositol 5 monophosphate (PtdIns5P) at bacterial entry sites, colocalizing with phosphorylated Akt.
  • S. flexneri-induced Akt phosphorylation requires IpgD, and ectopic IpgD expression or PtdIns5P addition triggers Akt phosphorylation.
  • PtdIns5P production activates class IA PI 3-kinase through tyrosine phosphorylation, enhancing host cell survival.

Conclusions:

  • Shigella flexneri employs IpgD to produce PtdIns5P, a novel mechanism for activating the PI 3-kinase/Akt pathway.
  • This bacterial-induced signaling pathway plays a significant role in modulating host cell responses, including promoting survival.

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