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The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model

BACKGROUND: Phage therapy is the therapeutic use of bacteriophages to treat highly drug resistant bacterial infections. The current surge in bacteriophage therapy is motivated mainly because of the emergence of antibiotic-resistant bacteria in clinics. This study evaluated the therapeutic potential...

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Autores principales: Manohar, Prasanth, Nachimuthu, Ramesh, Lopes, Bruno S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119258/
https://www.ncbi.nlm.nih.gov/pubmed/30170558
http://dx.doi.org/10.1186/s12866-018-1234-4
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author Manohar, Prasanth
Nachimuthu, Ramesh
Lopes, Bruno S.
author_facet Manohar, Prasanth
Nachimuthu, Ramesh
Lopes, Bruno S.
author_sort Manohar, Prasanth
collection PubMed
description BACKGROUND: Phage therapy is the therapeutic use of bacteriophages to treat highly drug resistant bacterial infections. The current surge in bacteriophage therapy is motivated mainly because of the emergence of antibiotic-resistant bacteria in clinics. This study evaluated the therapeutic potential of three bacteriophages isolated against Escherichia coli ec311, Klebsiella pneumoniae kp235 and Enterobacter cloacae el140 strains using Galleria mellonella. The in vitro activity of three different phages belonging to Podoviridae and Myoviridae families was studied by the double agar overlay method against multi-drug resistant strains. Larval survivability studies were performed to evaluate the potential of phages against infection using G. mellonella. RESULTS: All the three phages were found to have potential to infect the host bacterial strains. For in vivo studies it was observed that E. coli and E. cloacae infected larvae, should be treated with three phage doses (20 μL, 10(4) PFU/mL) at 6 h interval to achieve 100% survival rate. But in the case of K. pneumoniae, a single phage dose treatment showed promising outcome. When mixed bacterial infections (all three bacterial cultures at 10(8) CFU/mL) were tested, minimum of four doses of phage cocktail (three phages) at 6 h interval was necessary to recover the larvae. All the results were confirmed by enumerating bacteria from the larvae. CONCLUSION: Our data shows that although in vitro studies showed high infectivity of phages, for in vivo models multiple phage doses were required for effective treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-018-1234-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-61192582018-09-05 The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model Manohar, Prasanth Nachimuthu, Ramesh Lopes, Bruno S. BMC Microbiol Research Article BACKGROUND: Phage therapy is the therapeutic use of bacteriophages to treat highly drug resistant bacterial infections. The current surge in bacteriophage therapy is motivated mainly because of the emergence of antibiotic-resistant bacteria in clinics. This study evaluated the therapeutic potential of three bacteriophages isolated against Escherichia coli ec311, Klebsiella pneumoniae kp235 and Enterobacter cloacae el140 strains using Galleria mellonella. The in vitro activity of three different phages belonging to Podoviridae and Myoviridae families was studied by the double agar overlay method against multi-drug resistant strains. Larval survivability studies were performed to evaluate the potential of phages against infection using G. mellonella. RESULTS: All the three phages were found to have potential to infect the host bacterial strains. For in vivo studies it was observed that E. coli and E. cloacae infected larvae, should be treated with three phage doses (20 μL, 10(4) PFU/mL) at 6 h interval to achieve 100% survival rate. But in the case of K. pneumoniae, a single phage dose treatment showed promising outcome. When mixed bacterial infections (all three bacterial cultures at 10(8) CFU/mL) were tested, minimum of four doses of phage cocktail (three phages) at 6 h interval was necessary to recover the larvae. All the results were confirmed by enumerating bacteria from the larvae. CONCLUSION: Our data shows that although in vitro studies showed high infectivity of phages, for in vivo models multiple phage doses were required for effective treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-018-1234-4) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-31 /pmc/articles/PMC6119258/ /pubmed/30170558 http://dx.doi.org/10.1186/s12866-018-1234-4 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Manohar, Prasanth
Nachimuthu, Ramesh
Lopes, Bruno S.
The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model
title The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model
title_full The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model
title_fullStr The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model
title_full_unstemmed The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model
title_short The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model
title_sort therapeutic potential of bacteriophages targeting gram-negative bacteria using galleria mellonella infection model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119258/
https://www.ncbi.nlm.nih.gov/pubmed/30170558
http://dx.doi.org/10.1186/s12866-018-1234-4
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