We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
WASH-driven actin polymerization is required for efficient mycobacterial phagosome maturation arrest.
- Authors
Kolonko, Margot; Geffken, Anna Christina; Blumer, Tanja; Hagens, Kristine; Schaible, Ulrich Emil; Hagedorn, Monica
- Abstract
Pathogenic mycobacteria survive in phagocytic host cells primarily as a result of their ability to prevent fusion of their vacuole with lysosomes, thereby avoiding a bactericidal environment. The molecular mechanisms to establish and maintain this replication compartment are not well understood. By combining molecular and microscopical approaches we show here that after phagocytosis the actin nucleation-promoting factor WASH associates and generates F-actin on the mycobacterial vacuole. Disruption of WASH or depolymerization of F-actin leads to the accumulation of the proton-pumping V- ATPase around the mycobacterial vacuole, its acidification and reduces the viability of intracellular mycobacteria. This effect is observed for M . marinum in the model phagocyte D ictyostelium but also for M . marinum and M . tuberculosis in mammalian phagocytes. This demonstrates an evolutionarily conserved mechanism by which pathogenic mycobacteria subvert the actin-polymerization activity of WASH to prevent phagosome acidification and maturation, as a prerequisite to generate and maintain a replicative niche.
- Subjects
ACTIN; POLYMERIZATION; MYCOBACTERIA; PATHOGENIC bacteria; PHAGOCYTOSIS; PHAGOSOMES; MOLECULAR microbiology; LYSOSOMES
- Publication
Cellular Microbiology, 2014, Vol 16, Issue 2, p232
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1111/cmi.12217