Enterohemorrhagic Escherichia coli effector EspL2 induces actin microfilament aggregation through annexin 2 activation
Enterohemorrhagic Escherichia coli effector EspL2 induces actin microfilament aggregation through annexin 2 activation
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DOI：
10.1111/j.1462-5822.2008.01256.x
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发表时间：
2009-02-01
影响因子：
3.4
通讯作者：
Tobe, Toru
中科院分区：
文献类型：
--
作者：
Miyahara, Akira;Nakanishi, Noriko;Tobe, Toru
肠出血性大肠杆菌（EHEC）通过III型分泌系统（T3SS）将毒力因子输送到宿主细胞中，发挥细菌致病性。 EHEC 编码 20 多个 III 型分泌系统传递的效应子家族，这些效应子家族在不同的感染阶段具有不同的功能，并能够成功感染。其中之一 EspL2 在 EHEC O157:H7 Sakai 的 SpLE3 噬菌体样元件上编码，并且在各种 EHEC 菌株中高度保守。在这里，我们表明，在递送至宿主细胞后，EspL2 在贴壁细菌下积累，聚合的 F-肌动蛋白也是如此。表达 EspL2 的 EHEC 形成三维、浓缩的微集落，宿主细胞将富含 F-肌动蛋白的细胞骨架上的质膜突起延伸到其中。 EspL2 直接结合 F-肌动蛋白聚集膜联蛋白 2，从而增加其活性。此外，膜联蛋白 2 的去除消除了 EspL2 依赖性的浓缩微集落形成和 F-肌动蛋白聚集。 EspL2 诱导的宿主质膜的伪足状突起与细菌相互作用并支持细菌的定植，独立于 Tir 介导的肌动蛋白聚合。因此，EspL2 通过增加膜联蛋白 2 聚集 Tir 诱导的 F-肌动蛋白的能力以及通过改变宿主细胞膜的形态来支持有效的定植。
Enterohemorrhagic Escherichia coli (EHEC) delivers virulence factors into host cells through the type III secretion system (T3SS) to exert the bacterial pathogenicity. EHEC encodes more than 20 type III secretion system-delivered families of effectors that have different functions at different infectious stages and enable a successful infection. One of them, EspL2, is encoded on the SpLE3 phage-like element in EHEC O157:H7 Sakai and is well conserved among various EHEC strains. Here we show that, after delivery into host cells, EspL2 accumulated under adherent bacteria, as did polymerized F-actin. EspL2-expressing EHEC formed three-dimensional, condensed microcolonies, into which the host cell extended plasma membrane protrusions on an F-actin-rich cytoskeleton. EspL2 bound F-actin-aggregating annexin 2 directly, increasing its activity. In addition, annexin 2 depletion abolished the EspL2-dependent formation of condensed microcolonies and F-actin aggregation. The EspL2-induced pseudopod-like protrusion of the host plasma membrane interacted with and supported colonization by the bacteria, independent of Tir-mediated actin polymerization. Thus, EspL2 supports efficient colonization by increasing annexin 2's ability to aggregate Tir-induced F-actin and by modifying the morphology of the host cell membrane.