Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis

被引：388

作者：

Vergne, I

Chua, J

Lee, HH

Lucas, M

Belisle, J

Deretic, V ^{[1
]}

机构：

[1] Univ New Mexico, Sch Med, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA

[2] Univ New Mexico, Sch Med, Dept Cell Biol & Physiol, Albuquerque, NM 87131 USA

[3] Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 11期

关键词：

macrophage; phagosome; tuberculosis; lysosome; phosphatidylinositol; 3-phosphate;

D O I：

10.1073/pnas.0409716102

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：4033 / 4038

页数：6

共 40 条

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