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伴侣蛋白-尖端黏附素复合物对于 CFA/I 菌毛生物发生的协同激活至关重要。

Chaperone-tip adhesin complex is vital for synergistic activation of CFA/I fimbriae biogenesis.

机构信息

Center of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States of America.

出版信息

PLoS Pathog. 2020 Oct 2;16(10):e1008848. doi: 10.1371/journal.ppat.1008848. eCollection 2020 Oct.

DOI:10.1371/journal.ppat.1008848
PMID:33007034
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7531860/
Abstract

Colonization factor CFA/I defines the major adhesive fimbriae of enterotoxigenic Escherichia coli and mediates bacterial attachment to host intestinal epithelial cells. The CFA/I fimbria consists of a tip-localized minor adhesive subunit, CfaE, and thousands of copies of the major subunit CfaB polymerized into an ordered helical rod. Biosynthesis of CFA/I fimbriae requires the assistance of the periplasmic chaperone CfaA and outer membrane usher CfaC. Although the CfaE subunit is proposed to initiate the assembly of CFA/I fimbriae, how it performs this function remains elusive. Here, we report the establishment of an in vitro assay for CFA/I fimbria assembly and show that stabilized CfaA-CfaB and CfaA-CfaE binary complexes together with CfaC are sufficient to drive fimbria formation. The presence of both CfaA-CfaE and CfaC accelerates fimbria formation, while the absence of either component leads to linearized CfaB polymers in vitro. We further report the crystal structure of the stabilized CfaA-CfaE complex, revealing features unique for biogenesis of Class 5 fimbriae.

摘要

定植因子 CFA/I 定义了肠产毒性大肠杆菌的主要黏附性菌毛，并介导细菌与宿主肠道上皮细胞的附着。CFA/I 菌毛由一个定位于顶端的小黏附性亚基 CfaE 和数千个聚合成长有序螺旋杆的主要亚基 CfaB 组成。CFA/I 菌毛的生物合成需要周质伴侣蛋白 CfaA 和外膜通道蛋白 CfaC 的协助。尽管 CfaE 亚基被提议启动 CFA/I 菌毛的组装，但它如何执行此功能仍然难以捉摸。在这里，我们报告了建立体外 CFA/I 菌毛组装测定法，并表明稳定的 CfaA-CfaB 和 CfaA-CfaE 二元复合物以及 CfaC 足以驱动菌毛形成。CfaA-CfaE 和 CfaC 的存在都能加速菌毛的形成，而任何一种成分的缺失都会导致体外线性化的 CfaB 聚合物。我们进一步报告了稳定的 CfaA-CfaE 复合物的晶体结构，揭示了类 5 菌毛生物发生的独特特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/c846e0a6f7b1/ppat.1008848.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/e34df74788be/ppat.1008848.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/9919bb27ff19/ppat.1008848.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/2407a449585b/ppat.1008848.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/6f7dceebccd6/ppat.1008848.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/b9015a3593d9/ppat.1008848.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/c846e0a6f7b1/ppat.1008848.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/e34df74788be/ppat.1008848.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/9919bb27ff19/ppat.1008848.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/2407a449585b/ppat.1008848.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/6f7dceebccd6/ppat.1008848.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/b9015a3593d9/ppat.1008848.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d57/7531860/c846e0a6f7b1/ppat.1008848.g006.jpg

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