Mycobacterium tuberculosisglycosylated phosphatidylinositol causes phagosome maturation arrest

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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 howMycobacterium tuberculosiscauses phagosome maturation arrest. A glycosylatedM. tuberculosisphosphatidylinositol [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 theM. tuberculosisproduct responsible for the inhibition of phagosomal maturation.