A coat protein on phagosomes involved in the intracellular survival of mycobacteria

Mycobacteria are intracellular pathogens that can survive within macrophage phagosomes, thereby evading host defense strategies by largely unknown mec hanisms. We have identified a WD repeat host protein that was recruited to and actively retained on phagosomes by living, but not dead, mycobacteria. This protein, termed TACO, represents a component of the phagosome coat tha t is normally released prior to phagosome fusion with or maturation into ly sosomes. In macrophages lacking TACO, mycobacteria were readily transported to lysosomes followed by their degradation. Expression of TACO in nonmacro phages prevented lysosomal delivery of mycobacteria and prolonged their int racellular survival. Active retention of TACO on phagosomes by living mycob acteria thus represents a mechanism preventing cargo delivery to lysosomes, allowing mycobacteria to survive within macrophages.