<i>Mycobacterium tuberculosis</i> glycosylated phosphatidylinositol causes phagosome maturation arrest

TLDR

Mycobacterium tuberculosis blocks phagosome maturation in macrophages, a key factor driving the global tuberculosis burden. The study aims to determine how M. tuberculosis induces phagosome maturation arrest. Glycosylated phosphatidylinositol ManLAM disrupts lysosomal cargo acquisition and syntaxin‑6 delivery from the trans‑Golgi, specifically inhibiting the PI3K‑dependent pathway and PI3P‑binding effectors.

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.