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Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function
Bacterial neonatal meningitis results in high mortality and morbidity rates for those affected. Although improvements in diagnosis and treatment have led to a decline in mortality rates, morbidity rates have remained relatively unchanged. Bacterial resistance to antibiotics in this clinical setting...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264188/ https://www.ncbi.nlm.nih.gov/pubmed/32483257 http://dx.doi.org/10.1038/s41598-020-65867-4 |
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author | Møller-Olsen, Christian Ross, Toby Leppard, Keith N. Foisor, Veronica Smith, Corinne Grammatopoulos, Dimitris K. Sagona, Antonia P. |
author_facet | Møller-Olsen, Christian Ross, Toby Leppard, Keith N. Foisor, Veronica Smith, Corinne Grammatopoulos, Dimitris K. Sagona, Antonia P. |
author_sort | Møller-Olsen, Christian |
collection | PubMed |
description | Bacterial neonatal meningitis results in high mortality and morbidity rates for those affected. Although improvements in diagnosis and treatment have led to a decline in mortality rates, morbidity rates have remained relatively unchanged. Bacterial resistance to antibiotics in this clinical setting further underlines the need for developing other technologies, such as phage therapy. We exploited an in vitro phage therapy model for studying bacterial neonatal meningitis based on Escherichia coli (E. coli) EV36, bacteriophage (phage) K1F and human cerebral microvascular endothelial cells (hCMECs). We show that phage K1F is phagocytosed and degraded by constitutive- and PAMP-dependent LC3-assisted phagocytosis and does not induce expression of inflammatory cytokines TNFα, IL-6, IL-8 or IFNβ. Additionally, we observed that phage K1F temporarily decreases the barrier resistance of hCMEC cultures, a property that influences the barrier permeability, which could facilitate the transition of immune cells across the endothelial vessel in vivo. Collectively, we demonstrate that phage K1F can infect intracellular E. coli EV36 within hCMECs without themselves eliciting an inflammatory or defensive response. This study illustrates the potential of phage therapy targeting infections such as bacterial neonatal meningitis and is an important step for the continued development of phage therapy targeting antibiotic-resistant bacterial infections generally. |
format | Online Article Text |
id | pubmed-7264188 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72641882020-06-05 Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function Møller-Olsen, Christian Ross, Toby Leppard, Keith N. Foisor, Veronica Smith, Corinne Grammatopoulos, Dimitris K. Sagona, Antonia P. Sci Rep Article Bacterial neonatal meningitis results in high mortality and morbidity rates for those affected. Although improvements in diagnosis and treatment have led to a decline in mortality rates, morbidity rates have remained relatively unchanged. Bacterial resistance to antibiotics in this clinical setting further underlines the need for developing other technologies, such as phage therapy. We exploited an in vitro phage therapy model for studying bacterial neonatal meningitis based on Escherichia coli (E. coli) EV36, bacteriophage (phage) K1F and human cerebral microvascular endothelial cells (hCMECs). We show that phage K1F is phagocytosed and degraded by constitutive- and PAMP-dependent LC3-assisted phagocytosis and does not induce expression of inflammatory cytokines TNFα, IL-6, IL-8 or IFNβ. Additionally, we observed that phage K1F temporarily decreases the barrier resistance of hCMEC cultures, a property that influences the barrier permeability, which could facilitate the transition of immune cells across the endothelial vessel in vivo. Collectively, we demonstrate that phage K1F can infect intracellular E. coli EV36 within hCMECs without themselves eliciting an inflammatory or defensive response. This study illustrates the potential of phage therapy targeting infections such as bacterial neonatal meningitis and is an important step for the continued development of phage therapy targeting antibiotic-resistant bacterial infections generally. Nature Publishing Group UK 2020-06-01 /pmc/articles/PMC7264188/ /pubmed/32483257 http://dx.doi.org/10.1038/s41598-020-65867-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Møller-Olsen, Christian Ross, Toby Leppard, Keith N. Foisor, Veronica Smith, Corinne Grammatopoulos, Dimitris K. Sagona, Antonia P. Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function |
title | Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function |
title_full | Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function |
title_fullStr | Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function |
title_full_unstemmed | Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function |
title_short | Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function |
title_sort | bacteriophage k1f targets escherichia coli k1 in cerebral endothelial cells and influences the barrier function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264188/ https://www.ncbi.nlm.nih.gov/pubmed/32483257 http://dx.doi.org/10.1038/s41598-020-65867-4 |
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