吞噬体
效应器
微生物学
分泌物
生物
结核分枝杆菌
细胞生物学
细胞内寄生虫
细胞内
肺结核
生物化学
医学
病理
作者
Christian Xander,Rajagopalan Saranathan,William R. Jacobs,Miriam Braunstein
摘要
ABSTRACT Mycobacterium tuberculosis ( Mtb ) is an intracellular pathogen that survives and grows in macrophages. A mechanism used by Mtb to achieve intracellular survival is to secrete effector molecules that arrest the normal process of phagosome maturation. Through phagosome maturation arrest (PMA), Mtb remains in an early phagosome and avoids delivery to degradative phagolysosomes. One PMA effector of Mtb is the secreted SapM phosphatase. Because the host target of SapM, phosphatidylinositol-3-phosphate (PI 3 P), is located on the cytosolic face of the phagosome, SapM needs to not only be released by the mycobacteria but also travel out of the phagosome to carry out its function. To date, the only mechanism known for Mtb molecules to leave the phagosome is phagosome permeabilization by the ESX-1 secretion system. To understand this step of SapM function in PMA, we generated identical in-frame sapM mutants in both the attenuated Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine strain, which lacks the ESX-1 system, and Mtb . Characterization of these mutants demonstrated that SapM is required for PMA in BCG and Mtb . Further, by establishing a role for SapM in PMA in BCG, and subsequently in a Mtb mutant lacking the ESX-1 system, we demonstrated that the role of SapM does not require ESX-1. We further determined that ESX-2 or ESX-4 is also not required for SapM to function in PMA. These results indicate that SapM is a secreted effector of PMA in both BCG and Mtb , and that it can function independent of the known mechanism for Mtb molecules to leave the phagosome.
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