Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States.
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY, United States.
Front Cell Infect Microbiol. 2023 Jul 7;13:1232391. doi: 10.3389/fcimb.2023.1232391. eCollection 2023.
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 null strain, loss of does not impact invasion efficiency of . 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.
是一种专性细胞内病原体，积极促进上皮细胞的入侵。一种与毒力相关的 III 型分泌系统有助于衣原体的进入，至少有四个效应物已被描述，在此期间被部署。这两个与入侵相关的效应物，即易位膜相关效应物 A 和 B（TmeA 和 TmeB），被编码在一个双顺反子操纵子中。TmeA 直接激活宿主 N-WASP，刺激 Arp2/3 依赖的肌动蛋白聚合。根据目前的工作模型，TmeA 介导的 N-WASP 激活有助于入侵。TmeB 的功能尚未得到充分表征。与缺失株不同，缺失不会影响 的入侵效率。使用多个基因缺失株，我们提供的证据表明，在没有 TmeB 的情况下，TmeA 对于入侵是可有可无的。我们的数据表明，TmeB 的过度表达会干扰入侵，并且这种活性需要活跃的 Arp2/3 复合物。我们进一步表明，TmeB 能够干扰 Arp2/3 介导的肌动蛋白聚合。总的来说，这些数据表明 TmeA 和 TmeB 在入侵过程中具有相反的功能。这些研究提出了关于 TmeA、TmeB 和分支肌动蛋白聚合在衣原体进入过程中动态相互作用的有趣问题。
