沙眼衣原体TmeA通过N-WASP和TOCA-1相互作用促进底座样结构的形成。

IF 3.7 2区 生物学 Q2 MICROBIOLOGY
mSphere Pub Date : 2025-05-27 Epub Date: 2025-04-15 DOI:10.1128/msphere.00101-25
Alix McCullough, C A Jabeena, Steve Huang, Brianna Steiert, Robert Faris, Mary M Weber
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引用次数: 0

摘要

沙眼衣原体(C.t)是几种人类疾病的病原体,包括性传播感染衣原体和眼睛感染沙眼。作为一种专性的细胞内细菌病原体,入侵是建立感染和随后发病的关键。在入侵过程中,ct通过其III型分泌系统(T3SS)分泌效应蛋白,操纵宿主肌动蛋白细胞骨架调节,促进细菌进入。先前的研究发现T3SS效应蛋白TmeA是ct侵袭的关键因素,因为它招募和激活N-WASP。这种相互作用反过来激活Arp2/3复合体,驱动侵袭部位的细胞骨架重排,从而驱动ct摄取。在这项研究中,我们定义了N-WASP CRIB结构域在介导这种相互作用中的作用,并证明TmeA在激活N-WASP中发挥了Cdc42的模拟作用。此外,我们发现TOCA-1是另一种直接与TmeA相互作用的宿主蛋白。在其他细菌病原体中,特别是肠出血性大肠杆菌,N-WASP和TOCA-1被劫持介导基台形成。通过sirna介导的N-WASP和TOCA-1的敲低,然后通过透射电子显微镜,我们发现这两种蛋白对ct介导的基座状结构的形成都很重要。总的来说,这些发现扩大了我们对ct侵袭复杂性的理解,强调了tmea介导的与N-WASP和TOCA-1的相互作用如何促进基座样结构的形成,这可能代表了ct感染的早期步骤。重要性:沙眼衣原体(c.t.)是一种专性细胞内细菌病原体,对人类健康构成重大威胁,与多种疾病有关,包括最普遍的细菌性传播感染——衣原体和沙眼。衣原体感染通常无症状,但可导致严重的并发症,如不孕症、异位妊娠和宫颈癌和卵巢癌的风险增加。作为一种细胞内病原体,宿主细胞的侵袭对ct的存活和发病至关重要。在这项研究中,我们对ct侵袭效应蛋白TmeA与宿主蛋白N-WASP和TOCA-1之间的相互作用提供了新的见解,揭示了这两种宿主蛋白在ct感染的早期阶段都参与了基座样结构的形成。这些发现加深了我们对tmea介导的宿主细胞侵袭机制的理解,并强调了ct介导的发病机制的关键途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chlamydia trachomatis TmeA promotes pedestal-like structure formation through N-WASP and TOCA-1 interactions.

Chlamydia trachomatis (C.t.) is the causative agent of several human diseases, including the sexually transmitted infection chlamydia and the eye infection trachoma. As an obligate intracellular bacterial pathogen, invasion is critical for establishing infection and subsequent pathogenesis. During invasion, C.t. secretes effector proteins via its type III secretion system (T3SS), which manipulate host actin cytoskeletal regulation to promote bacterial entry. Previous studies identified the T3SS effector protein TmeA as a key factor in C.t. invasion, as it recruits and activates N-WASP. This interaction, in turn, activates the Arp2/3 complex, driving cytoskeletal rearrangements at the invasion site to drive C.t. uptake. In this study, we define the role of the N-WASP CRIB domain in mediating this interaction and demonstrate that TmeA functions as a mimic of Cdc42 as part of its established role in activating N-WASP. Additionally, we identified TOCA-1 as another host protein that directly interacts with TmeA. In other bacterial pathogens, notably an enterohemorrhagic E. coli, N-WASP and TOCA-1 are hijacked to mediate pedestal formation. Using siRNA-mediated knockdown of N-WASP and TOCA-1, followed by transmission electron microscopy, we found that both proteins are important for C.t.-mediated pedestal-like structure formation. Collectively, these findings expand our understanding of the intricacies of C.t. invasion, highlighting how TmeA-mediated interactions with N-WASP and TOCA-1 contribute to pedestal-like structure formation, which may represent an early step in C.t. infection.

Importance: Chlamydia trachomatis (C.t.) is an obligate intracellular bacterial pathogen that poses a significant threat to human health, being associated with various diseases, including chlamydia-the most prevalent bacterial sexually transmitted infection-and trachoma. Although often asymptomatic, chlamydia infections can lead to severe complications, such as infertility, ectopic pregnancy, and an increased risk of cervical and ovarian cancers. As an intracellular pathogen, host cell invasion is critical for C.t. survival and pathogenesis. In this study, we provide new insights into the interactions between the C.t. invasion effector protein TmeA and the host proteins N-WASP and TOCA-1, revealing that both host proteins are involved in pedestal-like structure formation during early stages of C.t. infection. These findings deepen our understanding of the mechanisms underlying TmeA-mediated host cell invasion and highlight a key pathway contributing to C.t.-mediated pathogenesis.

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来源期刊
mSphere
mSphere Immunology and Microbiology-Microbiology
CiteScore
8.50
自引率
2.10%
发文量
192
审稿时长
11 weeks
期刊介绍: mSphere™ is a multi-disciplinary open-access journal that will focus on rapid publication of fundamental contributions to our understanding of microbiology. Its scope will reflect the immense range of fields within the microbial sciences, creating new opportunities for researchers to share findings that are transforming our understanding of human health and disease, ecosystems, neuroscience, agriculture, energy production, climate change, evolution, biogeochemical cycling, and food and drug production. Submissions will be encouraged of all high-quality work that makes fundamental contributions to our understanding of microbiology. mSphere™ will provide streamlined decisions, while carrying on ASM''s tradition for rigorous peer review.
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