已知带有细菌病原体嗜肺军团菌的吞噬体富含磷脂酰肌醇4-磷酸(PtdIns4P),这对于锚定其毒力因子的子集以及可能与支持细胞内细菌生长的含军团菌液泡(LCV)的生物发生有关的信号事件很重要。在这里,我们证明了效应子MavQ是一种磷酸肌醇3激酶,可特异性催化磷脂酰肌醇(PtdIns)转化为PtdIns3P。MavQ的产物随后被效应物LepB磷酸化以产生PtdIns(3,4)P2,其3-磷酸随后被另一个效应物SidF去除以产生PtdIns4P。我们还表明,MavQ与LCV相关,并且ΔmavQ突变体在PtdIns4P结合效应子的锚定中显示出表型,类似于ΔlepB或ΔsidF突变体。我们的结果建立了嗜肺乳杆菌通过由MavQ组成的催化轴从头生物合成PtdIns4P的机制,LepB,和其吞噬体表面的SidF。
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 ∆mavQ mutant displays phenotypes in the anchoring of a PtdIns4P-binding effector similar to those of ∆lepB or ∆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.