Actin recruitment to the Chlamydia inclusion is spatiotemporally regulated by a mechanism that requires host and bacterial factors.
Actin recruitment to the Chlamydia inclusion is spatiotemporally regulated by a mechanism that requires host and bacterial factors.
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DOI：
10.1371/journal.pone.0046949
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hybiske K
中科院分区：
文献类型：
--
作者：
Chin E;Kirker K;Zuck M;James G;Hybiske K
在发育生长结束时退出宿主细胞的能力是细胞内细菌衣原体的关键步骤。一种退出策略，挤出，是由参与肌动蛋白聚合的宿主信号通路介导的。在这里，我们表明，肌动蛋白被招募到衣原体包涵体作为一个晚期事件，发生在感染后20小时（hpi），仅在细胞亚群。从20到68 hpi，这种事件的患病率和程度显着增加，肌动蛋白涂层与挤出强烈相关。与其他细胞内病原体的报道相反，衣原体内含物上的肌动蛋白成核并没有“闪烁”，而是表现出中度的解聚动力学。通过使用小分子试剂选择性地破坏宿主信号通路参与肌动蛋白成核，调节肌动蛋白聚合动力学，并禁用衣原体蛋白的合成和分泌，我们进一步表明，宿主和细菌蛋白质所需的肌动蛋白外壳的形成。宿主或细菌信号传导途径的瞬时破坏导致所有感染细胞中的外套迅速损失，并减少挤出形成。抑制衣原体III型分泌也导致包涵体上肌动蛋白结合的快速丧失，从而暗示衣原体效应蛋白是与宿主肌动蛋白成核因子（如formins）接合的中心因子。总之，我们的数据阐明了宿主和细菌驱动的过程，通过该过程，致密的肌动蛋白基质动态地成核并维持在衣原体包涵体上。这种晚期事件并不普遍存在于群体中的所有感染细胞中，并且在衣原体的整个发育周期中的流行率和程度上不断升级，最终通过挤出从宿主细胞中退出。启动肌动蛋白招聘衣原体似乎是新颖的，并可能作为一个上游决定因素的挤出机制。
The ability to exit host cells at the end of their developmental growth is a critical step for the intracellular bacterium Chlamydia. One exit strategy, extrusion, is mediated by host signaling pathways involved with actin polymerization. Here, we show that actin is recruited to the chlamydial inclusion as a late event, occurring after 20 hours post-infection (hpi) and only within a subpopulation of cells. This event increases significantly in prevalence and extent from 20 to 68 hpi, and actin coats strongly correlated with extrusions. In contrast to what has been reported for other intracellular pathogens, actin nucleation on Chlamydia inclusions did not ‘flash’, but rather exhibited moderate depolymerization dynamics. By using small molecule agents to selectively disrupt host signaling pathways involved with actin nucleation, modulate actin polymerization dynamics and also to disable the synthesis and secretion of chlamydial proteins, we further show that host and bacterial proteins are required for actin coat formation. Transient disruption of either host or bacterial signaling pathways resulted in rapid loss of coats in all infected cells and a reduction in extrusion formation. Inhibition of Chlamydia type III secretion also resulted in rapid loss of actin association on inclusions, thus implicating chlamydial effector proteins(s) as being central factors for engaging with host actin nucleating factors, such as formins. In conclusion, our data illuminate the host and bacterial driven process by which a dense actin matrix is dynamically nucleated and maintained on the Chlamydia inclusion. This late stage event is not ubiquitous for all infected cells in a population, and escalates in prevalence and extent throughout the developmental cycle of Chlamydia, culminating with their exit from the host cell by extrusion. The initiation of actin recruitment by Chlamydia appears to be novel, and may serve as an upstream determinant of the extrusion mechanism.
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影响因子：
2.9
作者：
DeMay, Bradley S.;Meseroll, Rebecca A.;Gladfelter, Amy S.
通讯作者：
Gladfelter, Amy S.
DOI：
10.1038/nrm2867
发表时间：
2010-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.0603044103
发表时间：
2006-10-17
影响因子：
11.1
作者：
Jewett, Travis J.;Fischer, Elizabeth R.;Hackstadt, Ted
通讯作者：
Hackstadt, Ted
影响因子：
6.7
作者：
Johnston, Simon A.;May, Robin C.
通讯作者：
May, Robin C.
影响因子：
3.1
作者：
Dong, F;Su, H;Zhong, GM
通讯作者：
Zhong, GM