Molecular and Cellular Mechanisms of Shigella flexneri Dissemination.
Molecular and Cellular Mechanisms of Shigella flexneri Dissemination.
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DOI：
10.3389/fcimb.2016.00029
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发表时间：
2016
影响因子：
5.7
通讯作者：
Agaisse H
中科院分区：
文献类型：
--
作者：
Agaisse H
细胞内病原体福氏志贺菌是人类细菌性痢疾的病原体。该疾病的特征在于肠细胞的细菌侵入、通过细胞间直接传播而在结肠上皮内传播以及肠粘膜的大量炎症。在这里，我们回顾了支持S的机制。弗氏传播。传播过程主要依赖于肌动蛋白在细菌极的组装，其推动病原体穿过原代感染细胞的胞质溶胶。极性肌动蛋白组装由细菌自转运蛋白家族成员IcsA的极性表达支持，IcsA招募N-WASP/ARP 2/3肌动蛋白组装机制。当运动的细菌遇到细胞-细胞接触时，它们形成质膜突起，突起到相邻的细胞中。除了依赖于ARP 2/3的肌动蛋白组装机制之外，突起的形成还依赖于formins和myosins。通过突起颈部的塌陷，突起分解为空泡，导致形成称为空泡样突起（VLP）的中间膜结合隔室。VLP的形成需要突起中的酪氨酸激酶和磷酸肌醇信号传导，这依赖于细菌3型分泌系统（T3 SS）的完整性。T3 SS也是通过T3 SS移位酶IpaB和IpaC以及效应蛋白VirA和IcsB的活性来逃离双膜空泡所必需的。支持包膜生物发生的许多因素有助于IcsA暴露和维持在细菌极，包括LPS合成，膜蛋白酶和周质伴侣。虽然特征较少，但在细菌传播的背景下T3 SS的组装和功能也依赖于支持包膜生物发生的因素。最后，传播过程需要病原体通过转录和转录后机制适应各种细胞区室。
The intracellular pathogen Shigella flexneri is the causative agent of bacillary dysentery in humans. The disease is characterized by bacterial invasion of intestinal cells, dissemination within the colonic epithelium through direct spread from cell to cell, and massive inflammation of the intestinal mucosa. Here, we review the mechanisms supporting S. flexneri dissemination. The dissemination process primarily relies on actin assembly at the bacterial pole, which propels the pathogen throughout the cytosol of primary infected cells. Polar actin assembly is supported by polar expression of the bacterial autotransporter family member IcsA, which recruits the N-WASP/ARP2/3 actin assembly machinery. As motile bacteria encounter cell-cell contacts, they form plasma membrane protrusions that project into adjacent cells. In addition to the ARP2/3-dependent actin assembly machinery, protrusion formation relies on formins and myosins. The resolution of protrusions into vacuoles occurs through the collapse of the protrusion neck, leading to the formation of an intermediate membrane-bound compartment termed vacuole-like protrusions (VLPs). VLP formation requires tyrosine kinase and phosphoinositide signaling in protrusions, which relies on the integrity of the bacterial type 3 secretion system (T3SS). The T3SS is also required for escaping double membrane vacuoles through the activity of the T3SS translocases IpaB and IpaC, and the effector proteins VirA and IcsB. Numerous factors supporting envelope biogenesis contribute to IcsA exposure and maintenance at the bacterial pole, including LPS synthesis, membrane proteases, and periplasmic chaperones. Although less characterized, the assembly and function of the T3SS in the context of bacterial dissemination also relies on factors supporting envelope biogenesis. Finally, the dissemination process requires the adaptation of the pathogen to various cellular compartments through transcriptional and post-transcriptional mechanisms.