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Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function
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Møller-Olsen, Christian, Ross, Toby, Leppard, Keith, Foisor, Veronica, Smith, Corinne J., Grammatopoulos, Dimitris and Sagona, Antonia P. (2020) Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function. Scientific Reports, 10 . 8903 . doi:10.1038/s41598-020-65867-4 ISSN 2045-2322.
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Official URL: https://doi.org/10.1038/s41598-020-65867-4
Abstract
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.
Item Type: | Journal Article | ||||||||||||
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Subjects: | R Medicine > RJ Pediatrics | ||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Meningitis in children, Meningitis, Bacterial diseases -- Research, Children -- Diseases -- Treatment, Meningitis -- Prevention, Bacteriophages -- Therapeutic use | ||||||||||||
Journal or Publication Title: | Scientific Reports | ||||||||||||
Publisher: | Nature Publishing Group | ||||||||||||
ISSN: | 2045-2322 | ||||||||||||
Official Date: | 2 June 2020 | ||||||||||||
Dates: |
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Volume: | 10 | ||||||||||||
Article Number: | 8903 | ||||||||||||
DOI: | 10.1038/s41598-020-65867-4 | ||||||||||||
Status: | Peer Reviewed | ||||||||||||
Publication Status: | Published | ||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||
Date of first compliant deposit: | 18 May 2020 | ||||||||||||
Date of first compliant Open Access: | 4 June 2020 | ||||||||||||
RIOXX Funder/Project Grant: |
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