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Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis.
TLDR
It is shown that the exclusion ofPI3P from live mycobacterial phagosomes can be only transiently reversed by Ca2+ fluxes, and that live M. tuberculosis secretes a lipid phosphatase, SapM, that hydrolyzes PI3P, inhibits phagosome-late endosome fusion in vitro, and contributes to inhibition of phagosomal maturation. Expand
Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest
TLDR
Findings identify ManLAM as the M. tuberculosis product responsible for the inhibition of phagosomal maturation, which underlies the tuberculosis pandemic involving 2 billion people. Expand
Tuberculosis Toxin Blocking Phagosome Maturation Inhibits a Novel Ca2+/Calmodulin-PI3K hVPS34 Cascade
TLDR
The interference of the trafficking toxin LAM with the calmodulin-dependent production of PI3P described here ensures long-term M. tuberculosis residence in vacuoles sequestered away from the bactericidal and antigen-processing organelles in infected macrophages. Expand
Rab14 is critical for maintenance of Mycobacterium tuberculosis phagosome maturation arrest
TLDR
A critical role for the small GTPase Rab14 is demonstrated in maintaining mycobacterial phagosome maturation block and enables myc Cobacterium tuberculosis phagosomes to maintain early endosomal characteristics and avoid late endOSomal/lysosomal degradative components. Expand
Cell biology of mycobacterium tuberculosis phagosome.
TLDR
The fundamental trafficking processes targeted by M. tuberculosis and the mycobacterial products that interfere with phagosomal maturation are reviewed. Expand
Induction of p38 Mitogen-activated Protein Kinase Reduces Early Endosome Autoantigen 1 (EEA1) Recruitment to Phagosomal Membranes*
TLDR
It is shown that p38 MAPK activity contributes to the arrest of M. tuberculosis phagosome maturation and a negative regulatory role of p38 in phagolysosome biogenesis is demonstrated. Expand
Mechanism of Inducible Nitric Oxide Synthase Exclusion from Mycobacterial Phagosomes
TLDR
The mechanism underlying this process, whereby mycobacteria affect the scaffolding protein EBP50, which normally binds to iNOS and links it to the actin cytoskeleton, is reported, which is consistent with a model for the block in iN OS association with myCobacterial phagosomes as a mechanism dependent primarly on reduced E BP50 recruitment. Expand
Higher order Rab programming in phagolysosome biogenesis
TLDR
It is shown that Rab22a defines the critical checkpoint for Rab7 conversion on phagosomes, allowing or disallowing organellar transition into a late endosomal compartment and preventing Rab7 acquisition and blocking phagolysosomal biogenesis. Expand
Mycobacterium tuberculosis phagosome maturation arrest: mycobacterial phosphatidylinositol analog phosphatidylinositol mannoside stimulates early endosomal fusion.
TLDR
The effects of PIM, along with the previously reported action of LAM, suggest that M. tuberculosis has evolved a two-prong strategy to modify its intracellular niche: its products block acquisition of late endosomal/lysosomal constituents, while facilitating fusion with early endOSomal compartments. Expand
A tale of two lipids: Mycobacterium tuberculosis phagosome maturation arrest.
TLDR
Mycobacterium tuberculosis persistence in human populations relies on its ability to inhibit phagosomal maturation, which includes the action of mycobacterial lipid products, which mimic mammalian phosphatidylinositols, targeting host cell membrane trafficking processes. Expand
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