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Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest.


ABSTRACT: The tubercle bacillus parasitizes macrophages by inhibiting phagosome maturation into the phagolysosome. This phenomenon underlies the tuberculosis pandemic involving 2 billion people. We report here how Mycobacterium tuberculosis causes phagosome maturation arrest. A glycosylated M. tuberculosis phosphatidylinositol [mannose-capped lipoarabinomannan (ManLAM)] interfered with the phagosomal acquisition of the lysosomal cargo and syntaxin 6 from the trans-Golgi network. ManLAM specifically inhibited the pathway dependent on phosphatidylinositol 3-kinase activity and phosphatidylinositol 3-phosphate-binding effectors. These findings identify ManLAM as the M. tuberculosis product responsible for the inhibition of phagosomal maturation.

SUBMITTER: Fratti RA 

PROVIDER: S-EPMC154363 | biostudies-literature | 2003 Apr

REPOSITORIES: biostudies-literature

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Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest.

Fratti Rutilio A RA   Chua Jennifer J   Vergne Isabelle I   Deretic Vojo V  

Proceedings of the National Academy of Sciences of the United States of America 20030417 9


The tubercle bacillus parasitizes macrophages by inhibiting phagosome maturation into the phagolysosome. This phenomenon underlies the tuberculosis pandemic involving 2 billion people. We report here how Mycobacterium tuberculosis causes phagosome maturation arrest. A glycosylated M. tuberculosis phosphatidylinositol [mannose-capped lipoarabinomannan (ManLAM)] interfered with the phagosomal acquisition of the lysosomal cargo and syntaxin 6 from the trans-Golgi network. ManLAM specifically inhibi  ...[more]

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