Chlamydia trachomatis TmeA Directly Activates N-WASP To Promote Actin Polymerization and Functions Synergistically with TarP during Invasion.
Chlamydia trachomatis TmeA Directly Activates N-WASP To Promote Actin Polymerization and Functions Synergistically with TarP during Invasion.
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DOI：
10.1128/mbio.02861-20
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发表时间：
2021-01-19
期刊：
影响因子：
6.4
通讯作者：
Fields KA
中科院分区：
文献类型：
--
作者：
Keb G;Ferrell J;Scanlon KR;Jewett TJ;Fields KA
沙眼衣原体的遗传易处理性的增加正在加速表征这种专性细胞内寄生虫的独特感染生物学的能力。这些努力使人们对与关键毒力要求相关的分子事件有了更深入的了解。沙眼衣原体是一种重要的人类病原体，是一种专性细胞内寄生虫。非专职吞噬细胞的入侵代表了感染过程中的关键步骤，并可能促进了冗余机制和进入途径的进化。像许多其他病毒和侵入性细菌病原体一样，操纵宿主细胞骨架是衣原体进入的焦点。随着遗传技术的出现，C。例如，通过荧光报告的等位基因交换诱变（FRAEM）产生完整的基因缺失，为阐明细菌因子在这些复杂途径中的作用提供了重要的工具。III型分泌伴侣Slc 1在入侵过程中指导至少四种效应物的递送。其中两个，TarP和TmeA，与肌动蛋白网络的操纵有关，并且对于正常水平的入侵是必不可少的。TarP的功能已得到很好的确立，而TmeA的特征则不太清楚。我们利用衣原体遗传学和邻近标记，在这里提供的证据表明，TmeA直接靶向主机N-WASP，以促进Arp 2/3依赖的肌动蛋白聚合。我们的工作还表明，TmeA和TarP影响单独的，但协同的途径，以完成衣原体进入。这些数据进一步支持了这样一种认识，即被简化论者基因组限制的病原体保留了在感染过程中投入大量资源来完成瓶颈步骤的能力。
The increasing genetic tractability of Chlamydia trachomatis is accelerating the ability to characterize the unique infection biology of this obligate intracellular parasite. These efforts are leading to a greater understanding of the molecular events associated with key virulence requirements. Chlamydia trachomatis is a medically significant human pathogen and is an epithelial-tropic obligate intracellular parasite. Invasion of nonprofessional phagocytes represents a crucial step in the infection process and has likely promoted the evolution of a redundant mechanism and routes of entry. Like many other viral and invasive bacterial pathogens, manipulation of the host cell cytoskeleton represents a focal point in Chlamydia entry. The advent of genetic techniques in C. trachomatis, such as creation of complete gene deletions via fluorescence-reported allelic exchange mutagenesis (FRAEM), is providing important tools to unravel the contributions of bacterial factors in these complex pathways. The type III secretion chaperone Slc1 directs delivery of at least four effectors during the invasion process. Two of these, TarP and TmeA, have been associated with manipulation of actin networks and are essential for normal levels of invasion. The functions of TarP are well established, whereas TmeA is less well characterized. We leverage chlamydial genetics and proximity labeling here to provide evidence that TmeA directly targets host N-WASP to promote Arp2/3-dependent actin polymerization. Our work also shows that TmeA and TarP influence separate, yet synergistic pathways to accomplish chlamydial entry. These data further support an appreciation that a pathogen, confined by a reductionist genome, retains the ability to commit considerable resources to accomplish bottle-neck steps during the infection process.