Bacterial outer membrane vesicles provide an alternative pathway for trafficking of Escherichia coli O157 type III secreted effectors to epithelial cells.
Bacterial outer membrane vesicles provide an alternative pathway for trafficking of Escherichia coli O157 type III secreted effectors to epithelial cells.
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外膜囊泡（OMV）是革兰氏阴性菌分泌的脂蛋白体。它们的分泌通过过渡到宿主内环境而增强，并且OMV在发病过程中起关键作用。肠出血性大肠杆菌O157（EHEC）可引起人类腹泻病，可溶性毒素包括志贺样毒素，有助于疾病的严重程度和临床并发症，如溶血性尿毒综合征已被证明与OMV相关。除了志贺样毒素外，肠出血性大肠杆菌还产生III型分泌系统（T3SS），T3SS效应物与体内定植和疾病严重程度相关。在这里，我们表明，III型分泌的基板，包括translocators和效应器被纳入OMV的存在和不存在的功能T3SS。与野生型EHEC脱落的囊泡相比，具有非功能性T3SS的EHEC菌株脱落更多的OMV，并且囊泡以加速的动力学进入宿主细胞。T3SS效应器易位的内膜蛋白受体（Tir）从OMV运输到宿主细胞中并定位于膜。然而，它在宿主细胞膜上的聚集和与细菌细胞膜的共定位是依赖于内膜的。我们表明，OMV交付的Tir可以交叉互补效应缺陷型肠出血性大肠杆菌菌株，并促进基座的形成。总之，这些数据表明OMV提供了递送EHEC T3SS货物的替代途径，并且囊泡相关效应物在宿主细胞内从OMV释放并可以保留生物活性。细菌可以将蛋白质货物包装成纳米级的膜泡，这些膜泡从细菌膜脱落并释放到环境中。在这里，我们报告了一种名为肠出血性大肠杆菌O157（EHEC）的致病菌使用其膜泡（外膜囊泡）包装其3型分泌系统的组分并将其送入宿主细胞，在那里它们可以操纵宿主信号通路，包括参与感染反应的信号通路，如免疫。通常，EHEC使用针状装置将这些成分注射到宿主细胞中，但将它们包装到被宿主细胞吸收的膜泡中是另一种传递方式，可以绕过对功能性注射系统的需要。
Outer membrane vesicles (OMVs) are proteoliposomes shed by Gram-negative bacteria. Their secretion is enhanced by the transition into the intra-host milieu, and OMVs play critical roles during pathogenesis. Enterohemorrhagic Escherichia coli O157 (EHEC) can cause diarrheal disease in humans, and soluble toxins including Shiga-like toxins that contribute to disease severity and clinical complications like hemolytic uremic syndrome have been shown to be OMV associated. In addition to Shiga-like toxins, EHEC produces a type III secretion system (T3SS), and T3SS effectors are associated with colonization and disease severity in vivo. Here, we show that type III secreted substrates including translocators and effectors are incorporated into OMVs both in the presence and absence of a functional T3SS. EHEC strains with non-functional T3SS shed more OMVs, and vesicles enter host cells with accelerated kinetics compared to vesicles shed from wild-type EHEC. The T3SS effector translocated intimin receptor (Tir) is trafficked from OMVs into host cells and localizes to the membrane. However, its clustering on the host membrane and co-localization with bacterial pedestals is intimin dependent. We show that OMV-delivered Tir can cross-complement an effector-deficient EHEC strain and promote pedestal formation. Together, these data demonstrate that OMVs provide an alternative pathway for the delivery of EHEC T3SS cargo and that vesicle associated effectors are released from OMVs inside host cells and can retain biological activity. Bacteria can package protein cargo into nanosized membrane blebs that are shed from the bacterial membrane and released into the environment. Here, we report that a type of pathogenic bacteria called enterohemorrhagic Escherichia coli O157 (EHEC) uses their membrane blebs (outer membrane vesicles) to package components of their type 3 secretion system and send them into host cells, where they can manipulate host signaling pathways including those involved in infection response, such as immunity. Usually, EHEC use a needle-like apparatus to inject these components into host cells, but packaging them into membrane blebs that get taken up by host cells is another way of delivery that can bypass the need for a functioning injection system.
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影响因子：
6.7
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Bielaszewska M;Rüter C;Bauwens A;Greune L;Jarosch KA;Steil D;Zhang W;He X;Lloubes R;Fruth A;Kim KS;Schmidt MA;Dobrindt U;Mellmann A;Karch H
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3.2
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