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Bacteria elevate extracellular adenosine to exploit host signaling for blood-brain barrier disruption
Bacterial meningitis remains a substantial cause of mortality worldwide and survivors may have severe lifelong disability. Although we know that meningeal bacterial pathogens must cross blood-central nervous system (CNS) barriers, the mechanisms which facilitate the virulence of these pathogens are...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549952/ https://www.ncbi.nlm.nih.gov/pubmed/32772676 http://dx.doi.org/10.1080/21505594.2020.1797352 |
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author | Zhao, Zunquan Shang, Xueyi Chen, Ying Zheng, Yuling Huang, Wenhua Jiang, Hua Lv, Qingyu Kong, Decong Jiang, Yongqiang Liu, Peng |
author_facet | Zhao, Zunquan Shang, Xueyi Chen, Ying Zheng, Yuling Huang, Wenhua Jiang, Hua Lv, Qingyu Kong, Decong Jiang, Yongqiang Liu, Peng |
author_sort | Zhao, Zunquan |
collection | PubMed |
description | Bacterial meningitis remains a substantial cause of mortality worldwide and survivors may have severe lifelong disability. Although we know that meningeal bacterial pathogens must cross blood-central nervous system (CNS) barriers, the mechanisms which facilitate the virulence of these pathogens are poorly understood. Here, we show that adenosine from a surface enzyme (Ssads) of Streptococcus suis facilitates this pathogen’s entry into mouse brains. Monolayer translocation assays (from the human cerebrovascular endothelium) and experiments using diverse inhibitors and agonists together demonstrate that activation of the A1 adenosine receptor signaling cascade in hosts, as well as attendant cytoskeleton remodeling, promote S. suis penetration across blood-CNS barriers. Importantly, our additional findings showing that Ssads orthologs from other bacterial species also promote their translocation across barriers suggest that exploitation of A1 AR signaling may be a general mechanism of bacterial virulence. |
format | Online Article Text |
id | pubmed-7549952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-75499522020-10-22 Bacteria elevate extracellular adenosine to exploit host signaling for blood-brain barrier disruption Zhao, Zunquan Shang, Xueyi Chen, Ying Zheng, Yuling Huang, Wenhua Jiang, Hua Lv, Qingyu Kong, Decong Jiang, Yongqiang Liu, Peng Virulence Research Paper Bacterial meningitis remains a substantial cause of mortality worldwide and survivors may have severe lifelong disability. Although we know that meningeal bacterial pathogens must cross blood-central nervous system (CNS) barriers, the mechanisms which facilitate the virulence of these pathogens are poorly understood. Here, we show that adenosine from a surface enzyme (Ssads) of Streptococcus suis facilitates this pathogen’s entry into mouse brains. Monolayer translocation assays (from the human cerebrovascular endothelium) and experiments using diverse inhibitors and agonists together demonstrate that activation of the A1 adenosine receptor signaling cascade in hosts, as well as attendant cytoskeleton remodeling, promote S. suis penetration across blood-CNS barriers. Importantly, our additional findings showing that Ssads orthologs from other bacterial species also promote their translocation across barriers suggest that exploitation of A1 AR signaling may be a general mechanism of bacterial virulence. Taylor & Francis 2020-08-10 /pmc/articles/PMC7549952/ /pubmed/32772676 http://dx.doi.org/10.1080/21505594.2020.1797352 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Zhao, Zunquan Shang, Xueyi Chen, Ying Zheng, Yuling Huang, Wenhua Jiang, Hua Lv, Qingyu Kong, Decong Jiang, Yongqiang Liu, Peng Bacteria elevate extracellular adenosine to exploit host signaling for blood-brain barrier disruption |
title | Bacteria elevate extracellular adenosine to exploit host signaling for blood-brain barrier disruption |
title_full | Bacteria elevate extracellular adenosine to exploit host signaling for blood-brain barrier disruption |
title_fullStr | Bacteria elevate extracellular adenosine to exploit host signaling for blood-brain barrier disruption |
title_full_unstemmed | Bacteria elevate extracellular adenosine to exploit host signaling for blood-brain barrier disruption |
title_short | Bacteria elevate extracellular adenosine to exploit host signaling for blood-brain barrier disruption |
title_sort | bacteria elevate extracellular adenosine to exploit host signaling for blood-brain barrier disruption |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549952/ https://www.ncbi.nlm.nih.gov/pubmed/32772676 http://dx.doi.org/10.1080/21505594.2020.1797352 |
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