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Morphologically Distinct Escherichia coli Bacteriophages Differ in Their Efficacy and Ability to Stimulate Cytokine Release In Vitro
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
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Number of Authors: 6
2016 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 7, 437Article in journal (Refereed) Published
Abstract [en]

Due to a global increase in the range and number of infections caused by multi resistant bacteria, phage therapy is currently experiencing a resurgence of interest. However, there are a number of well-known concerns over the use of phages to treat bacterial infections. In order to address concerns over safety and the poorly understood pharmacokinetics of phages and their associated cocktails, immunological characterization is required. In the current investigation, the immunogenicity of four distinct phages (taken from the main families that comprise the Caudovirales order) and their interaction with donor derived peripheral blood mononuclear cells and immortalized cell lines (HT-29 and Caco-2 intestinal epithelial cells) were investigated using standard immunological techniques. When exposed to high phage concentrations (10(9) PFU/well), cytokine driven inflammatory responses were induced from all cell types. Although phages appeared to inhibit the growth of intestinal epithelial cell lines, they also appear to be non-cytotoxic. Despite co-incubation with different cell types, phages maintained a high killing efficiency, reducing extended-spectrum betalactamase-producing Escherichia colinumbers by 1-4 log(10) compared to untreated controls. When provided with a suitable bacterial host, phages were also able to actively reproduce in the presence of human cells resulting in an approximately 2 log10 increase in phage titer compared to the initial inoculum. Through an increased understanding of the complex pharmacokinetics of phages, it may be possible to address some of the safety concerns surrounding phage preparations prior to creating new therapeutic strategies.

Place, publisher, year, edition, pages
2016. Vol. 7, 437
Keyword [en]
pharmacokinetics, phage therapy, cytokines, immune response, multi-resistant bacteria
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-129922DOI: 10.3389/fmicb.2016.00437ISI: 000373277300007OAI: oai:DiVA.org:su-129922DiVA: diva2:925735
Available from: 2016-05-03 Created: 2016-05-03 Last updated: 2016-05-03Bibliographically approved

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Khan Mirzaei, MohammadaliHaileselassie, YenenehCooper, CallumSverremark-Ekström, EvaNilsson, Anders S.
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Department of Molecular Biosciences, The Wenner-Gren Institute
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Frontiers in Microbiology
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