A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization
A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization
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DOI：
10.1046/j.1365-2958.2001.02230.x
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发表时间：
2001-01-01
影响因子：
3.6
通讯作者：
Galán, JE
中科院分区：
文献类型：
--
作者：
Zhou, DG;Chen, LM;Galán, JE
沙门氏菌致病性的中心特征是细菌进入非吞噬细胞的能力。细菌内化是细胞反应的结果，其特征在于Cdc 42-和Rac-依赖的肌动蛋白细胞骨架重排。这些反应是由通过称为III型的专门蛋白质分泌系统递送到宿主细胞中的细菌蛋白质的协调功能触发的。我们在这里报告，SopB，沙门氏菌肌醇多磷酸酶提供给宿主细胞的分泌系统，介导肌动蛋白细胞骨架重排和细菌进入Cdc 42依赖的方式。SopB表现出与细菌进入的其他两个效应物，Rho家族GTdR交换因子SopE和SopE 2重叠的功能。因此，缺乏这些蛋白质中的任何一种的沙门氏菌菌株可以以高效率进入细胞，而缺乏所有三种效应子的菌株则完全不能进入细胞。与磷酸肌醇代谢在沙门氏菌诱导的细胞反应中的重要作用一致，SopB的催化缺陷突变体未能刺激肌动蛋白细胞骨架重排和细菌进入。此外，细菌感染肠细胞导致InsP（1，4，5，6）P-4显著增加，InsP（5）消耗和磷脂酶C激活。与体内研究结果一致，纯化的SopB在体外特异性地将InsP（5）去磷酸化为Ins（1，4，5，6）P-4。令人惊讶的是，由沙门氏菌引起的磷酸肌醇通量并不完全由SopB引起。我们表明，SopB-独立的肌醇磷酸通量的内源性肌醇磷酸酶的SopE依赖性激活的后果。沙门氏菌通过替代机制刺激Rho GTP酶信号传导和磷酸肌醇代谢的能力是这种细菌病原体操纵宿主细胞功能的显著能力的一个例子。
A central feature of Salmonella pathogenicity is the bacterium's ability to enter into non-phagocytic cells. Bacterial internalization is the consequence of cellular responses characterized by Cdc42- and Rac-dependent actin cytoskeleton rearrangements. These responses are triggered by the co-ordinated function of bacterial proteins delivered into the host cell by a specialized protein secretion system termed type III. We report here that SopB, a Salmonella inositol polyphosphatase delivered to the host cell by this secretion system, mediates actin cytoskeleton rearrangements and bacterial entry in a Cdc42-dependent manner. SopB exhibits overlapping functions with two other effectors of bacterial entry, the Rho family GTPase exchange factors SopE and SopE2. Thus, Salmonella strains deficient in any one of these proteins can enter into cells at high efficiency, whereas a strain lacking all three effectors is completely defective for entry. Consistent with an important role for inositol phosphate metabolism in Salmonella-induced cellular responses, a catalytically defective mutant of SopB failed to stimulate actin cytoskeleton rearrangements and bacterial entry. Furthermore, bacterial infection of intestinal cells resulted in a marked increase in Ins(1,4,5,6)P-4, a consumption of InsP(5) and the activation of phospholipase C. In agreement with the in vivo findings, purified SopB specifically dephosphorylated InsP(5) to Ins(1,4,5,6)P-4 in vitro. Surprisingly, the inositol phosphate fluxes induced by Salmonella were not caused exclusively by SopB. We show that the SopB-independent inositol phosphate fluxes are the consequence of the SopE-dependent activation of an endogenous inositol phosphatase. The ability of Salmonella to stimulate Rho GTPases signalling and inositol phosphate metabolism through alternative mechanisms is an example of the remarkable ability of this bacterial pathogen to manipulate host cellular functions.