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Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts
Escherichia coli (E. coli) penetration of the blood-brain barrier (BBB) is the key step essential for the development of meningitis. In a recent paper (Nat Commun 9:2296), we identify Caspr1 as a host receptor for E. coli virulence factor IbeA to pave the way the penetration of bacteria through the...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Shared Science Publishers OG
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167520/ https://www.ncbi.nlm.nih.gov/pubmed/30280104 http://dx.doi.org/10.15698/mic2018.09.647 |
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author | Zhao, Wei-Dong Liu, Dong-Xin Chen, Yu-Hua |
author_facet | Zhao, Wei-Dong Liu, Dong-Xin Chen, Yu-Hua |
author_sort | Zhao, Wei-Dong |
collection | PubMed |
description | Escherichia coli (E. coli) penetration of the blood-brain barrier (BBB) is the key step essential for the development of meningitis. In a recent paper (Nat Commun 9:2296), we identify Caspr1 as a host receptor for E. coli virulence factor IbeA to pave the way the penetration of bacteria through the BBB. Bacterial IbeA interacts with endothelial Caspr1 to trigger intracellular focal adhesion kinase activation, leading to E. coli internalization into the brain endothelial cells. Importantly, endothelial knockout of Caspr1 in mice significantly reduced E. coli crossing through the BBB. Based on the results that extracellular aa 203-355 of Caspr1 bind with IbeA, we tested the blocking effect of recombinant Caspr1(203-355) peptides in neonatal rat model of meningitis. The results showed that Caspr1(203-355) peptides effectively attenuated E. coli penetration into the brain during meningitis, indicating that Caspr1(203-355) peptides could be used to neutralize the virulent IbeA to prevent meningitis. We further found that E. coli can directly invade into hippocampal neurons causing apoptosis which required the interaction between bacterial IbeA and neuronal Caspr1. These findings demonstrate that E. coli hijack Caspr1 as a host receptor for penetration of BBB and invasion of hippocampal neurons, resulting in progression of meningitis. |
format | Online Article Text |
id | pubmed-6167520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Shared Science Publishers OG |
record_format | MEDLINE/PubMed |
spelling | pubmed-61675202018-10-02 Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts Zhao, Wei-Dong Liu, Dong-Xin Chen, Yu-Hua Microb Cell Microbiology Escherichia coli (E. coli) penetration of the blood-brain barrier (BBB) is the key step essential for the development of meningitis. In a recent paper (Nat Commun 9:2296), we identify Caspr1 as a host receptor for E. coli virulence factor IbeA to pave the way the penetration of bacteria through the BBB. Bacterial IbeA interacts with endothelial Caspr1 to trigger intracellular focal adhesion kinase activation, leading to E. coli internalization into the brain endothelial cells. Importantly, endothelial knockout of Caspr1 in mice significantly reduced E. coli crossing through the BBB. Based on the results that extracellular aa 203-355 of Caspr1 bind with IbeA, we tested the blocking effect of recombinant Caspr1(203-355) peptides in neonatal rat model of meningitis. The results showed that Caspr1(203-355) peptides effectively attenuated E. coli penetration into the brain during meningitis, indicating that Caspr1(203-355) peptides could be used to neutralize the virulent IbeA to prevent meningitis. We further found that E. coli can directly invade into hippocampal neurons causing apoptosis which required the interaction between bacterial IbeA and neuronal Caspr1. These findings demonstrate that E. coli hijack Caspr1 as a host receptor for penetration of BBB and invasion of hippocampal neurons, resulting in progression of meningitis. Shared Science Publishers OG 2018-08-07 /pmc/articles/PMC6167520/ /pubmed/30280104 http://dx.doi.org/10.15698/mic2018.09.647 Text en https://creativecommons.org/licenses/by/4.0/ This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged. |
spellingShingle | Microbiology Zhao, Wei-Dong Liu, Dong-Xin Chen, Yu-Hua Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts |
title | Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts |
title_full | Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts |
title_fullStr | Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts |
title_full_unstemmed | Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts |
title_short | Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts |
title_sort | escherichia coli hijack caspr1 receptor to invade cerebral vascular and neuronal hosts |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167520/ https://www.ncbi.nlm.nih.gov/pubmed/30280104 http://dx.doi.org/10.15698/mic2018.09.647 |
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