Morphologically distinct Escherichia coli bacteriophages differ in their efficacy and ability to stimulate cytokine release in vitro

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 o...

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Main Authors: Mohammadali eKhan Mirzaei, Yeneneh eHaileselassie, Marit eNavis, Callum eCooper, Eva eSverremark-Ekström, Anders S Nilsson
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-03-01
Series:Frontiers in Microbiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00437/full
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spelling doaj-c3f1f6bf2f9745eda0cb883beed3cc832020-11-24T23:50:03ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-03-01710.3389/fmicb.2016.00437182155Morphologically distinct Escherichia coli bacteriophages differ in their efficacy and ability to stimulate cytokine release in vitroMohammadali eKhan Mirzaei0Yeneneh eHaileselassie1Marit eNavis2Callum eCooper3Eva eSverremark-Ekström4Anders S Nilsson5Stockholm UniversityStockholm UniversityStockholm UniversityStockholm UniversityStockholm UniversityStockholm UniversityDue 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 (109 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 beta-lactamase-producing Escherichia coli numbers by 1-4 log10 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.http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00437/fullCytokinesimmune responsepharmacokineticsphage therapyMulti-resistant bacteria
collection DOAJ
language English
format Article
sources DOAJ
author Mohammadali eKhan Mirzaei
Yeneneh eHaileselassie
Marit eNavis
Callum eCooper
Eva eSverremark-Ekström
Anders S Nilsson
spellingShingle Mohammadali eKhan Mirzaei
Yeneneh eHaileselassie
Marit eNavis
Callum eCooper
Eva eSverremark-Ekström
Anders S Nilsson
Morphologically distinct Escherichia coli bacteriophages differ in their efficacy and ability to stimulate cytokine release in vitro
Frontiers in Microbiology
Cytokines
immune response
pharmacokinetics
phage therapy
Multi-resistant bacteria
author_facet Mohammadali eKhan Mirzaei
Yeneneh eHaileselassie
Marit eNavis
Callum eCooper
Eva eSverremark-Ekström
Anders S Nilsson
author_sort Mohammadali eKhan Mirzaei
title Morphologically distinct Escherichia coli bacteriophages differ in their efficacy and ability to stimulate cytokine release in vitro
title_short Morphologically distinct Escherichia coli bacteriophages differ in their efficacy and ability to stimulate cytokine release in vitro
title_full Morphologically distinct Escherichia coli bacteriophages differ in their efficacy and ability to stimulate cytokine release in vitro
title_fullStr Morphologically distinct Escherichia coli bacteriophages differ in their efficacy and ability to stimulate cytokine release in vitro
title_full_unstemmed Morphologically distinct Escherichia coli bacteriophages differ in their efficacy and ability to stimulate cytokine release in vitro
title_sort morphologically distinct escherichia coli bacteriophages differ in their efficacy and ability to stimulate cytokine release in vitro
publisher Frontiers Media S.A.
series Frontiers in Microbiology
issn 1664-302X
publishDate 2016-03-01
description 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 (109 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 beta-lactamase-producing Escherichia coli numbers by 1-4 log10 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.
topic Cytokines
immune response
pharmacokinetics
phage therapy
Multi-resistant bacteria
url http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00437/full
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