The bacterial type three secretion system induces mechanoporation of vacuolar membranes

Léa Swistak1, Marvin Albert2, Camila Valenzuela1

  • 1Institut Pasteur, Université Paris Cité, CNRS UMR3691, Dynamics of Host-Pathogen Interactions Unit, Paris, France.

Plos Biology
|May 1, 2025
PubMed

Insights

Intracellular pathogens like Shigella flexneri breach host cell vacuoles using a specialized secretion system. This mechanism, called mechanoporation, creates holes in the vacuole, allowing bacterial entry into the cytosol.

Area of Science:

  • Microbiology
  • Cell Biology
  • Pathogenesis

Background:

  • Intracellular pathogens require access to the host cell cytosol for replication.
  • Vacuolar membranes pose a barrier that pathogens must overcome.
  • The mechanisms by which bacteria breach vacuolar membranes are not fully understood.

Purpose of the Study:

  • To investigate the mechanism by which Shigella flexneri breaches the host vacuolar membrane.
  • To visualize the role of the Type Three Secretion System (T3SS) in vacuole disruption.

Main Methods:

  • In-cell correlative light and electron microscopy (IC-CLEM) was employed.
  • Sequential steps of Shigella host cell entry were tracked.
  • The T3SS needle's interaction with the vacuolar membrane was visualized.

Main Results:

  • Shigella flexneri utilizes its T3SS to puncture the vacuolar membrane.
  • The T3SS needle directly creates holes in the vacuole.
  • This process, termed mechanoporation, facilitates entry into the host cytosol.

Conclusions:

  • Mechanoporation via a bacterial secretion system is a key mechanism for vacuolar membrane damage.
  • The T3SS plays a direct role in breaching the host vacuole for Shigella entry.
  • Understanding this process offers insights into bacterial pathogenesis and host-cell invasion strategies.

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