Chlamydia trachomatis TmeB antagonizes actin polymerization via direct interference with Arp2/3 activity.

Chlamydia trachomatis TmeB antagonizes actin polymerization via direct interference with Arp2/3 activity.
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DOI:
10.3389/fcimb.2023.1232391
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发表时间:
2023
影响因子:
5.7
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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沙眼衣原体是一种专性细胞内病原体,积极促进上皮细胞的侵袭。一个毒力相关的III型分泌系统有助于衣原体的进入,至少有四个效应器已被描述,在此期间部署。这些侵袭相关效应子中的两个,易位的膜相关效应子A和B(TmeA和TmeB),在双顺反子操纵子中编码。TmeA直接激活宿主N-WASP以刺激Arp 2/3依赖性肌动蛋白聚合。根据目前的工作模型,TmeA介导的N-WASP激活有助于入侵。TmeB尚未进行功能表征。与tmeA无效菌株不同,tmeB的缺失不影响C的入侵效率。沙眼使用多个基因缺陷的菌株,我们提供的证据表明,TmeA在TmeB不存在的情况下是不适合入侵的。我们的数据表明,过多的TmeB干扰入侵,这种活动需要积极的Arp 2/3复合物。我们进一步表明,TmeB能够干扰Arp 2/3介导的肌动蛋白聚合。总的来说,这些数据表明TmeA和TmeB在入侵过程中表现出相反的功能。这些研究提出了有趣的问题,TmeA,TmeB,和分支肌动蛋白聚合在衣原体进入动态之间的相互作用。
Chlamydia trachomatis is an obligate intracellular pathogen that actively promotes invasion of epithelial cells. A virulence-associated type III secretion system contributes to chlamydial entry and at least four effectors have been described that are deployed during this time. Two of these invasion-related effectors, the translocated membrane-associated effectors A and B (TmeA and TmeB), are encoded in a bi-cistronic operon. TmeA directly activates host N-WASP to stimulate Arp2/3-dependent actin polymerization. According to current working models, TmeA-mediated N-WASP activation contributes to invasion. TmeB has not been functionally characterized. Unlike a tmeA null strain, loss of tmeB does not impact invasion efficiency of C. trachomatis. Using strains deficient for multiple genes, we provide evidence that TmeA is dispensable for invasion in the absence of TmeB. Our data indicate that overabundance of TmeB interferes with invasion and that this activity requires active Arp2/3 complex. We further show that TmeB is capable of interfering with Arp2/3-mediated actin polymerization. In aggregate, these data point to opposing functions for TmeA and TmeB that manifest during the invasion process. These studies raise intriguing questions regarding the dynamic interplay between TmeA, TmeB, and branched actin polymerization during chlamydial entry.
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