Molecular mechanisms of cell-cell spread of intracellular bacterial pathogens.

Molecular mechanisms of cell-cell spread of intracellular bacterial pathogens.
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DOI:
10.1098/rsob.130079
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发表时间:
2013-07-17
期刊:
影响因子:
5.8
通讯作者:
Ireton K
Ireton K
中科院分区:
生物学2区
文献类型:
--
作者:
Ireton K

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几种细菌病原体,包括单核细胞增生李斯特菌、福氏志贺氏菌和立克次氏体,已经进化出了在人体组织内积极传播的机制。传播是由病原体诱导的宿主丝状(F)-肌动蛋白的募集启动的。肌动蛋白在微生物后面形成一条尾巴,推动它穿过细胞质。然后,运动的病原体遇到宿主质膜,形成一个包含细菌的突起,被相邻的细胞吞噬。在过去的二十年里,在阐明F-肌动蛋白尾形成机制方面取得了很大进展。李斯特菌和志贺氏菌通过破坏宿主Arp 2/3复合物产生分支肌动蛋白丝的尾部。与此相反,立克次氏体通过细菌模拟真核生物的形成蛋白形成具有线性肌动蛋白丝的尾巴。与F-肌动蛋白尾形成相比,控制细菌突起的机制还不太清楚。然而,最近的研究结果强调了病原体操纵宿主细胞-细胞连接在传播中的重要性。李斯特菌产生一种可溶性蛋白,通过扰乱紧密连接来增强细菌突起。志贺氏菌突起通过网格蛋白介导的途径在“三细胞连接”-三个上皮细胞交叉处的专门膜区域被吞噬。这篇综述总结了过去在病原体传播中的主要发现,并重点介绍了肌动蛋白为基础的运动和细菌突起的形成和内化的最新进展。
Several bacterial pathogens, including Listeria monocytogenes, Shigella flexneri and Rickettsia spp., have evolved mechanisms to actively spread within human tissues. Spreading is initiated by the pathogen-induced recruitment of host filamentous (F)-actin. F-actin forms a tail behind the microbe, propelling it through the cytoplasm. The motile pathogen then encounters the host plasma membrane, forming a bacterium-containing protrusion that is engulfed by an adjacent cell. Over the past two decades, much progress has been made in elucidating mechanisms of F-actin tail formation. Listeria and Shigella produce tails of branched actin filaments by subverting the host Arp2/3 complex. By contrast, Rickettsia forms tails with linear actin filaments through a bacterial mimic of eukaryotic formins. Compared with F-actin tail formation, mechanisms controlling bacterial protrusions are less well understood. However, recent findings have highlighted the importance of pathogen manipulation of host cell–cell junctions in spread. Listeria produces a soluble protein that enhances bacterial protrusions by perturbing tight junctions. Shigella protrusions are engulfed through a clathrin-mediated pathway at ‘tricellular junctions’—specialized membrane regions at the intersection of three epithelial cells. This review summarizes key past findings in pathogen spread, and focuses on recent developments in actin-based motility and the formation and internalization of bacterial protrusions.
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