Related Experiment Videos
[Molecular and cellular bases of intestinal epithelial cell invasion by Shigella flexneri]
1Unité de pathogénie microbienne moléculaire, Inserm U 389, Institut Pasteur, Paris, France.
Abstract:
A key step in the pathogenesis of shigellosis is the capacity of the causative bacteria, shigellae, to invade colonic and rectal epithelial cells in humans. This invasive process encompasses several steps: entry into epithelial cells by induction of a macropinocytic event caused by secreted Ipa proteins. the bacterium then escapes from the vacuole and reaches the cytoplasmic compartment in which it divides rapidly and becomes motile via the expression of a surface protein, IcsA, whose polar localization achieves directed polymerization of actin filaments that push the bacterial body forward. Bacteria then engage the inner face of the cellular membrane in the junctional area and form protrusions allowing their passage into the adjacent cell. Lysis of the double membrane eventually allows access to the cytoplasmic compartment of the adjacent cell, thus providing the bacterium with a very efficient mechanism of epithelial colonization.
Insights
Shigella bacteria invade human colon cells using secreted proteins to enter cells and escape vacuoles. They then use actin-based motility to spread between cells, causing epithelial colonization and shigellosis.
Area of Science:
- Microbiology
- Cell Biology
- Pathogenesis
Context:
- Shigellosis is a severe diarrheal disease caused by Shigella bacteria.
- Bacterial invasion of host epithelial cells is critical for shigellosis pathogenesis.
- Understanding bacterial invasion mechanisms is key to developing treatments.
Purpose:
- To elucidate the multi-step process of Shigella invasion and intracellular replication within human colonic epithelial cells.
- To detail the roles of secreted Ipa proteins and surface protein IcsA in bacterial pathogenesis.
Summary:
- Shigella initiates invasion by inducing macropinocytosis via secreted Ipa proteins, followed by vacuolar escape into the cytoplasm.
- Intracellularly, Shigella divides, becomes motile through IcsA-mediated actin polymerization, and propels itself towards adjacent cells.
- The bacteria form membrane protrusions, lyse the double membrane, and access adjacent cell cytoplasm, facilitating efficient epithelial colonization.
Impact:
- Provides a detailed molecular understanding of Shigella's invasive strategy.
- Highlights key bacterial factors (Ipa proteins, IcsA) essential for pathogenesis.
- Informs potential therapeutic targets for preventing or treating shigellosis.