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1型菌毛杆状结构在介导宿主-病原体相互作用中的功能作用。

Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions.

作者信息

Spaulding Caitlin N, Schreiber Henry Louis, Zheng Weili, Dodson Karen W, Hazen Jennie E, Conover Matt S, Wang Fengbin, Svenmarker Pontus, Luna-Rico Areli, Francetic Olivera, Andersson Magnus, Hultgren Scott, Egelman Edward H

机构信息

Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, United States.

Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United States.

出版信息

Elife. 2018 Jan 18;7:e31662. doi: 10.7554/eLife.31662.

DOI:10.7554/eLife.31662
PMID:29345620
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5798934/
Abstract

Uropathogenic (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut. The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold for displaying the tip adhesin, FimH. We solved the 4.2 Å resolution structure of the type 1 pilus rod using cryo-electron microscopy. Residues forming the interactive surfaces that determine the mechanical properties of the rod were maintained by selection based on a global alignment of sequences. We identified mutations that did not alter pilus production in vitro but reduced the force required to unwind the rod. UPEC expressing these mutant pili were significantly attenuated in bladder infection and intestinal colonization in mice. This study elucidates an unappreciated functional role for the molecular spring-like property of type 1 pilus rods in host-pathogen interactions and carries important implications for other pilus-mediated diseases.

摘要

引起尿路感染（UTI）的尿路致病性大肠杆菌（UPEC）利用1型菌毛，一种伴侣-usher途径（CUP）菌毛，来引发尿路感染并在肠道中定殖。菌毛杆由重复的FimA亚基组成，为展示顶端黏附素FimH提供了一个结构支架。我们使用冷冻电子显微镜解析了1型菌毛杆的4.2 Å分辨率结构。通过基于序列全局比对的选择，维持了形成决定菌毛杆机械性能的相互作用表面的残基。我们鉴定出了在体外不改变菌毛产生但降低解开菌毛杆所需力的突变。表达这些突变菌毛的UPEC在小鼠膀胱感染和肠道定殖中显著减弱。这项研究阐明了1型菌毛杆的分子弹簧样特性在宿主-病原体相互作用中未被认识到的功能作用，并对其他菌毛介导的疾病具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fad3/5798934/6c5059127e9f/elife-31662-fig6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fad3/5798934/6c5059127e9f/elife-31662-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fad3/5798934/534e42ba95bb/elife-31662-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fad3/5798934/b9b8ed9e3529/elife-31662-fig5.jpg
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