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Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function

Authors: Christian Møller-Olsen; Toby Ross; Keith N. Leppard; Veronica Foisor; Corinne J. Smith; Dimitris K. Grammatopoulos; Antonia P. Sagona;

Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function

Abstract

AbstractBacterial 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.

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Subjects by Vocabulary

Microsoft Academic Graph classification: Phage therapy medicine.drug_class medicine.medical_treatment Antibiotics Biology medicine.disease_cause Neonatal meningitis Microbiology Proinflammatory cytokine Bacteriophage Immune system medicine Escherichia coli medicine.disease biology.organism_classification Tumor necrosis factor alpha

Library of Congress Subject Headings: lcsh:Medicine lcsh:Science lcsh:R lcsh:Q

Keywords

Cell biology, RJ, Microbiology, Models, Biological, Article, Meningitis, Bacterial, Phagocytosis, Escherichia coli, Humans, Bacteriophages, Phage Therapy, Cells, Cultured, Escherichia coli Infections, Focal Adhesions, Multidisciplinary, Brain, Endothelial Cells, Endothelium, Vascular, Microtubule-Associated Proteins

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  • citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    21
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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download
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
downloads
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21
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48
69
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