The type III secretion system apparatus determines the intracellular niche of bacterial pathogens
The type III secretion system apparatus determines the intracellular niche of bacterial pathogens
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III型分泌系统决定细菌病原体的细胞内生态位
DOI：
10.1073/pnas.1520699113
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发表时间：
2016-04-26
影响因子：
11.1
通讯作者：
Lesser, Cammie F.
中科院分区：
文献类型：
--
作者：
Du, Juan;Reeves, Analise Z.;Lesser, Cammie F.
在进入宿主细胞后，细胞内细菌病原体建立各种复制小生境。虽然一些改造吞噬体，其他迅速逃逸到受感染细胞的胞质溶胶。目前很少有人知道专业胞质内病原体，包括志贺氏菌，介导吞噬体逃逸。志贺氏菌，像许多其他革兰氏阴性细菌病原体一样，使用III型分泌系统将多种蛋白质（称为效应子）递送到宿主细胞中。在这里，使用一种创新的还原论为基础的方法，我们证明了引入一个功能性志贺氏菌III型分泌系统，但没有其效应子，大肠杆菌的实验室菌株是足以促进有效的空泡溶解和逃逸的热变性细菌进入上皮细胞的胞质溶胶。据我们所知，这是第一次建立了志贺氏菌III型分泌器（T3 SA）在介导吞噬体逃逸中的直接生理作用。此外，虽然T3 SA的蛋白质组分在细菌物种中具有中等程度的结构和功能保守性，但我们发现空泡溶解不是T3 SA的常见特征，因为耶尔森氏菌的无效应菌株仍然局限于吞噬体。此外，通过利用的功能性的移位器组件的志贺氏菌，沙门氏菌，和色杆菌的T3 SA，我们证明了一个单一的蛋白质组件的T3 SA translocon志贺氏菌IpaC，沙门氏菌SipC，或色杆菌CipC-决定的命运细胞内的病原体在上皮细胞和巨噬细胞。因此，这些发现已经确定了一个可能的范例，许多细胞内细菌病原体的复制生态位的建立。
Upon entry into host cells, intracellular bacterial pathogens establish a variety of replicative niches. Although some remodel phagosomes, others rapidly escape into the cytosol of infected cells. Little is currently known regarding how professional intracytoplasmic pathogens, including Shigella, mediate phagosomal escape. Shigella, like many other Gram-negative bacterial pathogens, uses a type III secretion system to deliver multiple proteins, referred to as effectors, into host cells. Here, using an innovative reductionist-based approach, we demonstrate that the introduction of a functional Shigella type III secretion system, but none of its effectors, into a laboratory strain of Escherichia coli is sufficient to promote the efficient vacuole lysis and escape of themodified bacteria into the cytosol of epithelial cells. This establishes for the first time, to our knowledge, a direct physiologic role for the Shigella type III secretion apparatus (T3SA) in mediating phagosomal escape. Furthermore, although protein components of the T3SA share a moderate degree of structural and functional conservation across bacterial species, we show that vacuole lysis is not a common feature of T3SA, as an effectorless strain of Yersinia remains confined to phagosomes. Additionally, by exploiting the functional interchangeability of the translocator components of the T3SA of Shigella, Salmonella, and Chromobacterium, we demonstrate that a single protein component of the T3SA translocon-Shigella IpaC, Salmonella SipC, or Chromobacterium CipC-determines the fate of intracellular pathogens within both epithelial cells and macrophages. Thus, these findings have identified a likely paradigm by which the replicative niche of many intracellular bacterial pathogens is established.