The crystal structure of the toxin EspC from enteropathogenic Escherichia coli reveals the mechanism that governs host cell entry and cytotoxicity.

IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-03-31 DOI:10.1080/19490976.2025.2483777
Akila U Pilapitiya, Lilian Hor, Jing Pan, Lakshmi C Wijeyewickrema, Robert N Pike, Denisse L Leyton, Jason J Paxman, Begoña Heras
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引用次数: 0

Abstract

Enteropathogenic E. coli (EPEC) is a significant cause of diarrhea, leading to high infant mortality rates. A key toxin produced by EPEC is the EspC autotransporter, which is regulated alongside genes from the locus of enterocyte effacement (LEE), which collectively result in the characteristic attaching and effacing lesions on the intestinal epithelium. In this study, we present the crystal structure of the EspC passenger domain (αEspC) revealing a toxin comprised a serine protease attached to a large β-helix with additional subdomains. Using various modified EspC expression constructs, alongside type III secretion system-mediated cell internalization assays, we dissect how the αEspC structural features enable toxin entry into the intestinal epithelium to cause cell cytotoxicity.

肠致病性大肠杆菌毒素EspC的晶体结构揭示了控制宿主细胞进入和细胞毒性的机制。
肠致病性大肠杆菌(EPEC)是腹泻的重要原因,导致婴儿死亡率高。EPEC产生的一种关键毒素是EspC自转运蛋白,它与肠细胞消退(LEE)位点的基因一起受到调节,这些基因共同导致肠上皮上的特征性附着和消退病变。在这项研究中,我们展示了EspC乘客结构域(αEspC)的晶体结构,揭示了一种毒素由丝氨酸蛋白酶组成,该蛋白酶附着在具有附加子结构域的大β-螺旋上。利用各种改良的EspC表达构建,以及III型分泌系统介导的细胞内化实验,我们剖析了αEspC的结构特征是如何使毒素进入肠上皮引起细胞毒性的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Gut Microbes
Gut Microbes Medicine-Microbiology (medical)
CiteScore
18.20
自引率
3.30%
发文量
196
审稿时长
10 weeks
期刊介绍: The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more. Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.
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