SopD acts cooperatively with SopB during Salmonella enterica serovar Typhimurium invasion
SopD acts cooperatively with SopB during Salmonella enterica serovar Typhimurium invasion
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DOI：
10.1111/j.1462-5822.2007.01000.x
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发表时间：
2007-12-01
影响因子：
3.4
通讯作者：
Brumell, John H.
中科院分区：
文献类型：
--
作者：
Bakowski, Malina A.;Cirulis, Judith T.;Brumell, John H.
细胞内细菌病原体鼠伤寒沙门氏菌（S.typhimurium）会在多种宿主中引起疾病。为了侵入宿主细胞并在宿主细胞中复制，这些细菌使用称为效应器的细菌蛋白颠覆宿主分子机制，并使用专门的蛋白质递送系统将其转移到宿主细胞中。其中一种效应子 SopD 会导致动物模型中鼠伤寒沙门氏菌的胃肠炎、全身毒力和持续存在。最近，SopD 与极化上皮细胞的侵袭有关，在这里我们研究了 SopD 介导的侵袭的特征。我们发现，SopD 在鼠伤寒沙门氏菌入侵过程中的膜裂变和巨胞饮体形成中发挥作用，这些事件先前表明是由 SopB 效应子介导的。我们进一步证明 SopD 与 SopB 合作在入侵期间促进这些事件。使用活细胞成像，我们表明 SopD-GFP 融合并不像之前描述的那样定位于 HeLa 细胞胞浆，而是与膜相关。当鼠伤寒沙门氏菌感染这些细胞时，SopD-GFP 被募集到入侵位点，并且这种募集需要 SopB 的磷酸酶活性。我们的研究结果证明了 SopD 在鼠伤寒沙门氏菌入侵期间操纵宿主细胞膜中的作用，并揭示了其与 SopB 协同作用的本质。
The intracellular bacterial pathogen, Salmonella enterica serovar Typhimurium (S. typhimurium), causes disease in a variety of hosts. To invade and replicate in host cells, these bacteria subvert host molecular machinery using bacterial proteins, called effectors, which they translocate into host cells using specialized protein delivery systems. One of these effectors, SopD, contributes to gastroenteritis, systemic virulence and persistence of S. typhimurium in animal models of infection. Recently, SopD has been implicated in invasion of polarized epithelial cells and here we investigate the features of SopD-mediated invasion. We show that SopD plays a role in membrane fission and macropinosome formation during S. typhimurium invasion, events previously shown to be mediated by the SopB effector. We further demonstrate that SopD acts cooperatively with SopB to promote these events during invasion. Using live cell imaging we show that a SopD-GFP fusion does not localize to HeLa cell cytosol as previously described, but instead is membrane associated. Upon S. typhimurium infection of these cells, SopD-GFP is recruited to the invasion site, and this recruitment required the phosphatase activity of SopB. Our findings demonstrate a role for SopD in manipulation of host-cell membrane during S. typhimurium invasion and reveal the nature of its cooperative action with SopB.