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Published on: January 6, 2014
Pseudomonas aeruginosa Transmigrates at Epithelial Cell-Cell Junctions, Exploiting Sites of Cell Division and
Guillaume Golovkine1,2,3,4, Eric Faudry1,2,3,4, Stéphanie Bouillot1,2,3,4
1University Grenoble Alpes, Grenoble, France.
Abstract:
To achieve systemic infection, bacterial pathogens must overcome the critical and challenging step of transmigration across epithelial barriers. This is particularly true for opportunistic pathogens such as Pseudomonas aeruginosa, an agent which causes nosocomial infections. Despite extensive study, details on the mechanisms used by this bacterium to transmigrate across epithelial tissues, as well as the entry sites it uses, remain speculative. Here, using real-time microscopy and a model epithelial barrier, we show that P. aeruginosa employs a paracellular transmigration route, taking advantage of altered cell-cell junctions at sites of cell division or when senescent cells are expelled from the cell layer. Once a bacterium transmigrates, it is followed by a cohort of bacteria using the same entry point. The basal compartment is then invaded radially from the initial penetration site. Effective transmigration and propagation require type 4 pili, the type 3 secretion system (T3SS) and a flagellum, although flagellum-deficient bacteria can occasionally invade the basal compartment from wounded areas. In the basal compartment, the bacteria inject the T3SS toxins into host cells, disrupting the cytoskeleton and focal contacts to allow their progression under the cells. Thus, P. aeruginosa exploits intrinsic host cell processes to breach the epithelium and invade the subcellular compartment.
Insights
Pseudomonas aeruginosa breaches epithelial barriers via a paracellular route, exploiting cell division and senescence. This opportunistic pathogen uses type 4 pili and the type 3 secretion system (T3SS) to cause systemic infections.
Area of Science:
- Microbiology
- Cell Biology
- Infectious Diseases
Background:
- Bacterial pathogens must cross epithelial barriers to cause systemic infections.
- Pseudomonas aeruginosa is an opportunistic pathogen responsible for nosocomial infections.
- Mechanisms and entry sites for P. aeruginosa epithelial transmigration remain unclear.
Purpose of the Study:
- To elucidate the mechanisms and entry sites used by P. aeruginosa for epithelial transmigration.
- To understand how P. aeruginosa invades host tissues and causes infection.
Main Methods:
- Real-time microscopy was employed to observe P. aeruginosa transmigration across a model epithelial barrier.
- The study analyzed bacterial behavior and host cell interactions during invasion.
Main Results:
- P. aeruginosa utilizes a paracellular route, entering through altered cell junctions during cell division or senescence.
- Transmigration is facilitated by type 4 pili and the type 3 secretion system (T3SS).
- In the basal compartment, P. aeruginosa injects T3SS toxins to disrupt host cell cytoskeleton and focal contacts, enabling further invasion.
Conclusions:
- P. aeruginosa exploits host cell processes, specifically altered cell junctions, to breach epithelial barriers.
- The bacterium uses a coordinated transmigration strategy, with subsequent bacteria following initial entry points.
- Successful invasion and propagation depend on T4P, T3SS, and flagella, highlighting key virulence factors.
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