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Morphologically Distinct Escherichia coli Bacteriophages Differ in Their Efficacy and Ability to Stimulate Cytokine Release In Vitro
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
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Antal upphovsmän: 62016 (Engelska)Ingår i: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 7, artikel-id 437Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
2016. Vol. 7, artikel-id 437
Nyckelord [en]
pharmacokinetics, phage therapy, cytokines, immune response, multi-resistant bacteria
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
URN: urn:nbn:se:su:diva-129922DOI: 10.3389/fmicb.2016.00437ISI: 000373277300007OAI: oai:DiVA.org:su-129922DiVA, id: diva2:925735
Tillgänglig från: 2016-05-03 Skapad: 2016-05-03 Senast uppdaterad: 2017-11-30Bibliografiskt granskad

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Av författaren/redaktören
Khan Mirzaei, MohammadaliHaileselassie, YenenehCooper, CallumSverremark-Ekström, EvaNilsson, Anders S.
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Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Frontiers in Microbiology
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