Host cell-dependent secretion and translocation of the LepA and LepB effectors of Legionella pneumophila
Host cell-dependent secretion and translocation of the LepA and LepB effectors of Legionella pneumophila
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DOI：
10.1111/j.1462-5822.2007.00899.x
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发表时间：
2007-07-01
影响因子：
3.4
通讯作者：
Shuman, Howard A.
中科院分区：
文献类型：
--
作者：
Chen, John;Reyes, Moraima;Shuman, Howard A.
嗜肺军团菌是引起军团病的革兰氏阴性细菌，军团病是一种急性的、常常致命的肺炎。L.嗜肺菌感染肺泡巨噬细胞，通过阻止吞噬体与溶酶体融合并避免吞噬体酸化来逃避吞噬细胞的抗微生物防御。然后细菌调节液泡的组成，使其具有内质网的特征。当细菌感染单细胞原生动物时，也会发生类似的事件。人们认为，淡水原生动物的复制为生物体提供了一个环境水库。几种效应蛋白通过Icm/Dot IV型分泌系统（TFSS）递送至宿主。其中一些已被证明参与军团菌吞噬体的运输。在这里，我们描述的能力的Icm/点TFSS易位两个效应，LepA和LepB，发挥作用的非裂解释放的军团菌从原生动物。我们报告说，转运的Lep蛋白被抑制剂，去乙酰化肌动蛋白丝和效应器可能会分泌到细胞外介质后，细胞接触。Lep蛋白质通过基因缺失而耗尽，导致溶解红细胞的能力增加。与此相反，含Lep的杂合蛋白的过表达似乎特异性地抑制Icm/Dot TFSS的活性，并且可能阻止对细胞内增殖至关重要的其他效应物的递送。
Legionella pneumophila is the Gram-negative bacterial agent of Legionnaires' disease, an acute, often fatal pneumonia. L. pneumophila infects alveolar macrophages, evading the antimicrobial defences of the phagocyte by preventing fusion of the phagosome with lysosomes and avoiding phagosome acidification. The bacteria then modulate the composition of the vacuole so that it takes on the characteristics of the endoplasmic reticulum. Similar events occur when the bacteria infect unicellular protozoa. It is thought that replication in fresh water protozoa provides an environmental reservoir for the organism. Several effector proteins are delivered to the host by the Icm/Dot type IV secretion system (TFSS). Some of these have been shown to participate in the trafficking of the Legionella phagosome. Here we describe the ability of the Icm/Dot TFSS to translocate two effectors, LepA and LepB, that play a role in the non-lytic release of Legionella from protozoa. We report that translocation of the Lep proteins is inhibited by agents that depolymerize actin filaments and that effectors may be secreted into the extracellular medium upon cell contact. Depletion of the Lep proteins by deletion of their genes results in increased ability to lyse red blood cells. In contrast, overexpression of Lep-containing hybrid proteins appears to specifically inhibit the activity of the Icm/Dot TFSS and may prevent the delivery of other effectors that are critical for intracellular multiplication.