Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis
Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis
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DOI：
10.1073/pnas.0409716102
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发表时间：
2005-03-15
影响因子：
11.1
通讯作者：
Deretic, V
中科院分区：
文献类型：
--
作者：
Vergne, I;Chua, J;Deretic, V
结核分枝杆菌活菌通过干扰巨噬细胞吞噬小体的生物发生而存活于巨噬细胞吞噬小体中。在这里，使用四维显微镜和体外测试，我们报告了含有活的和死亡的分枝杆菌的吞噬体之间的主要差异。磷脂酰肌醇3-磷酸(PI3P)是一种膜转运调节脂质，对吞噬体溶酶体成分的获取是必不可少的，它被保留在含有死亡分枝杆菌的吞噬小体上，但被活细菌从吞噬小体中清除。我们发现，活体分枝杆菌吞噬体内PI3P的排除只能被钙离子通量瞬时逆转，活体结核分枝杆菌分泌一种脂磷酸酶SAPM，该酶能降解PI3P，抑制体外吞噬小体-晚期内小体融合，并有助于抑制吞噬小体成熟。
Live Mycobacterium tuberculosis persists in macrophage phagosomes by interfering with phagolysosome biogenesis. Here, using four-dimensional microscopy and in vitro assays, we report the principal difference between phagosomes containing live and dead mycobacteria. Phosphatidylinositol 3-phosphate (PI3P), a membrane trafficking regulatory lipid essential for phagosomal acquisition of lysosomal constituents, is retained on phagosomes harboring dead mycobacteria but is continuously eliminated from phagosomes with live bacilli. We show that the exclusion of PI3P from live mycobacterial phagosomes can be only transiently reversed by Ca2+ fluxes, and that live M. tuberculosis secretes a lipid phosphatase, SapM, that hydrolyzes PI3P, inhibits phagosome-late endosome fusion in vitro, and contributes to inhibition of phagosomal maturation.