Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest.
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.
Fratti
Rutilio A
RA
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Chua
Jennifer
J
Vergne
Isabelle
I
Deretic
Vojo
V
D006031:Glycosylation; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D010586:Phagocytes / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010716:Phosphatidylinositols / Q000502:physiology*; D050765:Qa-SNARE Proteins; D033921:Vesicular Transport Proteins
D008565:Membrane Proteins; D010716:Phosphatidylinositols; D050765:Qa-SNARE Proteins; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; D019869:Phosphatidylinositol 3-Kinases