Tubercular mycobacteria can escape their proliferation niche and spread from cell to cell via an ejection structure
Event details
| Date | 08.01.2009 |
| Hour | 12:15 |
| Speaker | Thierry Soldati |
| Location | |
| Category | Conferences - Seminars |
Tubercular mycobacteria such as M. tuberculosis and M. marinum utilise common strategies to invade phagocytes of the innate immune system, manipulate their otherwise bactericidal phagocytic apparatus and increase the success of cell-to-cell transmission. M. marinum is the closest relative to the tuberculosis group of mycobacteria and provides a powerful model to study the pathogenesis of tuberculosis in genetically tractable model organisms, such as Drosophila and zebrafish. Using the soil amoeba Dictyostelium discoideum as a host, we have identified and characterized mycobacterial and host factors that modulate resistance to infection and cell-to-cell spreading (Hagedorn & Soldati, Cell Microbiol, 2007, 9:2716-33)
In particular, we discovered that both M. marinum and M. tuberculosis can escape from their vacuole into the cytosol, and are ejected from the cell through an F-actin structure, the ejectosome. This appears to be a conserved strategy because, upon infection of human peripheral blood monocytes and murine microglial cells, flotillin-1 accumulation at the M. marinum replication niche and vacuole rupture were also observed. Upon ejection of M. marinum, despite local loss of membrane integrity, neither host cell leakage nor lysis was observed. Ejection is crucial for the maintenance of an infection and is a concerted process that requires both host and pathogen factors. Disruption of the Dictyostelium gene for the RacH GTPase led to intracellular accumulation of bacteria. Also, no ejectosome was formed in cells infected with M. marinum lacking the major conserved mycobacterial virulence locus RD1. We propose that this specific strategy evolved as a necessity for the release of a cytosolic pathogen in a mutually beneficial manner, and discuss its evolutionary origin and relevance for dissemination of a mycobacterial infection.
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- General public
- Free
Contact
- Gisou van der Goot