Modulation of phagosome phosphoinositide dynamics by a Legionella phosphoinositide 3-kinase

The phagosome harboring the bacterial pathogen Legionella pneumophila is known to be enriched with phosphatidylinositol 4-phosphate (PtdIns4P), which is important for anchoring a subset of its virulence factors and potentially for signaling events implicated in the biogenesis of the Legionella-containing vacuole (LCV) that supports intracellular bacterial growth. Here we demonstrate that the effector MavQ is a phosphoinositide 3-kinase that specifically catalyzes the conversion of phosphatidylinositol (PtdIns) into PtdIns3P. The product of MavQ is subsequently phosphorylated by the effector LepB to yield PtdIns(3,4)P2, whose 3-phosphate is then removed by another effector SidF to generate PtdIns4P. We also show that MavQ is associated with the LCV and the increment mavQ mutant displays phenotypes in the anchoring of a PtdIns4P-binding effector similar to those of increment lepB or increment sidF mutants. Our results establish a mechanism of de novo PtdIns4P biosynthesis by L. pneumophila via a catalysis axis comprised of MavQ, LepB, and SidF on the surface of its phagosome.

Automated summary

The study reveals a mechanism of de novo PtdIns4P biosynthesis by Legionella pneumophila via a catalysis axis comprised of MavQ, LepB, and SidF on the surface of its phagosome.