Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Møller-Olsen, Christian, Ross, Toby, Leppard, Keith N., Foisor, Veronica, Smith, Corinne, Grammatopoulos, Dimitris K., Sagona, Antonia P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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
_version_ 1783540922992033792
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
work_keys_str_mv AT møllerolsenchristian bacteriophagek1ftargetsescherichiacolik1incerebralendothelialcellsandinfluencesthebarrierfunction
AT rosstoby bacteriophagek1ftargetsescherichiacolik1incerebralendothelialcellsandinfluencesthebarrierfunction
AT leppardkeithn bacteriophagek1ftargetsescherichiacolik1incerebralendothelialcellsandinfluencesthebarrierfunction
AT foisorveronica bacteriophagek1ftargetsescherichiacolik1incerebralendothelialcellsandinfluencesthebarrierfunction
AT smithcorinne bacteriophagek1ftargetsescherichiacolik1incerebralendothelialcellsandinfluencesthebarrierfunction
AT grammatopoulosdimitrisk bacteriophagek1ftargetsescherichiacolik1incerebralendothelialcellsandinfluencesthebarrierfunction
AT sagonaantoniap bacteriophagek1ftargetsescherichiacolik1incerebralendothelialcellsandinfluencesthebarrierfunction