The bacterial type three secretion system induces mechanoporation of vacuolar membranes
Endomembrane breaching is a crucial strategy employed by intracellular pathogens enclosed within vacuoles to access the nutrient-rich cytosol for intracellular replication. While bacteria use various mechanisms to compromise host membranes, the specific processes and factors involved are often unknown. Shigella flexneri, a major human pathogen, accesses the cytosol relying on the Type Three Secretion System (T3SS) and secreted effectors. Using in-cell correlative light and electron microscopy, we tracked the sequential steps of Shigella host cell entry. Moreover, we captured the T3SS, which projects a needle from the bacterial surface, in the process of puncturing holes in the vacuolar membrane. This initial puncture ensures disruption of the vacuole. Together this introduces the concept of mechanoporation via a bacterial secretion system as a crucial process for bacterial pathogen-induced membrane damage.
Authors
- Anna Sartori-Rupp (ORCID: https://orcid.org/0000-0001-8540-9910)
- Anastasia D. Gazi (ORCID: https://orcid.org/0000-0002-2922-3625)
- Keith T. Egger (ORCID: https://orcid.org/0000-0003-2119-3334)
- François Bontems (ORCID: https://orcid.org/0000-0002-4166-4845)
- Jost Enninga (ORCID: https://orcid.org/0000-0002-5218-349X)
- Elif Begüm Gökerküçük (ORCID: https://orcid.org/0000-0003-2213-4301)
- Matthijn Vos (ORCID: https://orcid.org/0000-0002-6046-9949)
- Léa Swistak (ORCID: https://orcid.org/0000-0002-5637-2415)
- Camila Valenzuela (ORCID: https://orcid.org/0000-0002-5642-6188)
- Jean-Yves Tinévez (ORCID: https://orcid.org/0000-0002-0998-4718)
- Marvin Albert (ORCID: https://orcid.org/0000-0003-2536-2545)
- Cammie F. Lesser (ORCID: https://orcid.org/0000-0002-1702-6333)
- Perrine Paul‐Gilloteaux (ORCID: https://orcid.org/0000-0002-4822-165X)
- Stéphane Tachon
Institutions
- Centre National de la Recherche Scientifique (FR)
- Institut de Chimie des Substances Naturelles (FR)
- Harvard University (US)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- Massachusetts General Hospital (US)
- Boston VA Research Institute (US)
- Nantes Université (FR)
Publication Details
- Journal
- PLoS Biology
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1371/journal.pbio.3003135
- Citations
- 2
- Primary Topic
- Vibrio bacteria research studies
- Type
- article
- Field-Weighted Citation Impact
- 3.60
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- European Research Council