Cargando…

Myoviridae phage PDX kills enteroaggregative Escherichia coli without human microbiome dysbiosis

INTRODUCTION: Bacteriophage therapy can be developed to target emerging diarrhoeal pathogens, but doing so in the absence of microbiome disruption, which occurs with antibiotic treatment, has not been established. AIM: Identify a therapeutic bacteriophage that kills diarrhoeagenic enteroaggregative...

Descripción completa

Detalles Bibliográficos
Autores principales: Cepko, Leah C. S., Garling, Eliotte E., Dinsdale, Madeline J., Scott, William P., Bandy, Loralee, Nice, Tim, Faber-Hammond, Joshua, Mellies, Jay L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Microbiology Society 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431101/
https://www.ncbi.nlm.nih.gov/pubmed/32011231
http://dx.doi.org/10.1099/jmm.0.001162
_version_ 1783571527815397376
author Cepko, Leah C. S.
Garling, Eliotte E.
Dinsdale, Madeline J.
Scott, William P.
Bandy, Loralee
Nice, Tim
Faber-Hammond, Joshua
Mellies, Jay L.
author_facet Cepko, Leah C. S.
Garling, Eliotte E.
Dinsdale, Madeline J.
Scott, William P.
Bandy, Loralee
Nice, Tim
Faber-Hammond, Joshua
Mellies, Jay L.
author_sort Cepko, Leah C. S.
collection PubMed
description INTRODUCTION: Bacteriophage therapy can be developed to target emerging diarrhoeal pathogens, but doing so in the absence of microbiome disruption, which occurs with antibiotic treatment, has not been established. AIM: Identify a therapeutic bacteriophage that kills diarrhoeagenic enteroaggregative Escherichia coli (EAEC) while leaving the human microbiome intact. METHODOLOGY: Phages from wastewater in Portland, OR, USA were screened for bacteriolytic activity by overlay assay. One isolated phage, PDX, was classified by electron microscopy and genome sequencing. A mouse model of infection determined whether the phage was therapeutic against EAEC. 16S metagenomic analysis of anaerobic cultures determined whether a normal human microbiome was altered by treatment. RESULTS: Escherichia virus PDX, a member of the strictly lytic family Myoviridae, killed a case-associated EAEC isolate from a child in rural Tennessee in a dose-dependent manner, and killed EAEC isolates from Columbian children. A single dose of PDX (multiplicity of infection: 100) 1 day post-infection reduced EAEC recovered from mouse faeces. PDX also killed EAEC when cultured anaerobically in the presence of human faecal bacteria. While the addition of EAEC reduced the β-diversity of the human microbiota, that of the cultures with either faeces alone, faeces with EAEC and PDX, or with just PDX phage was not different statistically. CONCLUSION: PDX killed EAEC isolate EN1E-0007 in vivo and in vitro, while not altering the diversity of normal human microbiota in anaerobic culture, and thus could be part of an effective therapy for children in developing countries and those suffering from EAEC-mediated traveller’s diarrhoea without causing dysbiosis.
format Online
Article
Text
id pubmed-7431101
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Microbiology Society
record_format MEDLINE/PubMed
spelling pubmed-74311012020-08-19 Myoviridae phage PDX kills enteroaggregative Escherichia coli without human microbiome dysbiosis Cepko, Leah C. S. Garling, Eliotte E. Dinsdale, Madeline J. Scott, William P. Bandy, Loralee Nice, Tim Faber-Hammond, Joshua Mellies, Jay L. J Med Microbiol Research Article INTRODUCTION: Bacteriophage therapy can be developed to target emerging diarrhoeal pathogens, but doing so in the absence of microbiome disruption, which occurs with antibiotic treatment, has not been established. AIM: Identify a therapeutic bacteriophage that kills diarrhoeagenic enteroaggregative Escherichia coli (EAEC) while leaving the human microbiome intact. METHODOLOGY: Phages from wastewater in Portland, OR, USA were screened for bacteriolytic activity by overlay assay. One isolated phage, PDX, was classified by electron microscopy and genome sequencing. A mouse model of infection determined whether the phage was therapeutic against EAEC. 16S metagenomic analysis of anaerobic cultures determined whether a normal human microbiome was altered by treatment. RESULTS: Escherichia virus PDX, a member of the strictly lytic family Myoviridae, killed a case-associated EAEC isolate from a child in rural Tennessee in a dose-dependent manner, and killed EAEC isolates from Columbian children. A single dose of PDX (multiplicity of infection: 100) 1 day post-infection reduced EAEC recovered from mouse faeces. PDX also killed EAEC when cultured anaerobically in the presence of human faecal bacteria. While the addition of EAEC reduced the β-diversity of the human microbiota, that of the cultures with either faeces alone, faeces with EAEC and PDX, or with just PDX phage was not different statistically. CONCLUSION: PDX killed EAEC isolate EN1E-0007 in vivo and in vitro, while not altering the diversity of normal human microbiota in anaerobic culture, and thus could be part of an effective therapy for children in developing countries and those suffering from EAEC-mediated traveller’s diarrhoea without causing dysbiosis. Microbiology Society 2020-02 2020-02-03 /pmc/articles/PMC7431101/ /pubmed/32011231 http://dx.doi.org/10.1099/jmm.0.001162 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License.
spellingShingle Research Article
Cepko, Leah C. S.
Garling, Eliotte E.
Dinsdale, Madeline J.
Scott, William P.
Bandy, Loralee
Nice, Tim
Faber-Hammond, Joshua
Mellies, Jay L.
Myoviridae phage PDX kills enteroaggregative Escherichia coli without human microbiome dysbiosis
title Myoviridae phage PDX kills enteroaggregative Escherichia coli without human microbiome dysbiosis
title_full Myoviridae phage PDX kills enteroaggregative Escherichia coli without human microbiome dysbiosis
title_fullStr Myoviridae phage PDX kills enteroaggregative Escherichia coli without human microbiome dysbiosis
title_full_unstemmed Myoviridae phage PDX kills enteroaggregative Escherichia coli without human microbiome dysbiosis
title_short Myoviridae phage PDX kills enteroaggregative Escherichia coli without human microbiome dysbiosis
title_sort myoviridae phage pdx kills enteroaggregative escherichia coli without human microbiome dysbiosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431101/
https://www.ncbi.nlm.nih.gov/pubmed/32011231
http://dx.doi.org/10.1099/jmm.0.001162
work_keys_str_mv AT cepkoleahcs myoviridaephagepdxkillsenteroaggregativeescherichiacoliwithouthumanmicrobiomedysbiosis
AT garlingeliottee myoviridaephagepdxkillsenteroaggregativeescherichiacoliwithouthumanmicrobiomedysbiosis
AT dinsdalemadelinej myoviridaephagepdxkillsenteroaggregativeescherichiacoliwithouthumanmicrobiomedysbiosis
AT scottwilliamp myoviridaephagepdxkillsenteroaggregativeescherichiacoliwithouthumanmicrobiomedysbiosis
AT bandyloralee myoviridaephagepdxkillsenteroaggregativeescherichiacoliwithouthumanmicrobiomedysbiosis
AT nicetim myoviridaephagepdxkillsenteroaggregativeescherichiacoliwithouthumanmicrobiomedysbiosis
AT faberhammondjoshua myoviridaephagepdxkillsenteroaggregativeescherichiacoliwithouthumanmicrobiomedysbiosis
AT melliesjayl myoviridaephagepdxkillsenteroaggregativeescherichiacoliwithouthumanmicrobiomedysbiosis