Metagenomic Analysis of Therapeutic PYO Phage Cocktails from 1997 to 2014

Phage therapy has regained interest in recent years due to the alarming spread of antibiotic resistance. Whilst phage cocktails are commonly sold in pharmacies in countries such as Georgia and Russia, this is not the case in western countries due to western regulatory agencies requiring a thorough c...

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Main Authors: Julia Villarroel, Mette Voldby Larsen, Mogens Kilstrup, Morten Nielsen
Format: Article
Language:English
Published: MDPI AG 2017-11-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/9/11/328
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author Julia Villarroel
Mette Voldby Larsen
Mogens Kilstrup
Morten Nielsen
author_facet Julia Villarroel
Mette Voldby Larsen
Mogens Kilstrup
Morten Nielsen
author_sort Julia Villarroel
collection DOAJ
description Phage therapy has regained interest in recent years due to the alarming spread of antibiotic resistance. Whilst phage cocktails are commonly sold in pharmacies in countries such as Georgia and Russia, this is not the case in western countries due to western regulatory agencies requiring a thorough characterization of the drug. Here, DNA sequencing of constituent biological entities constitutes a first step. The pyophage (PYO) cocktail is one of the main commercial products of the Georgian Eliava Institute of Bacteriophage, Microbiology and Virology and is used to cure skin infections. Since its first production in the 1930s, the composition of the cocktail has been periodically modified to add phages effective against emerging pathogenic strains. In this paper, we compared the composition of three PYO cocktails from 1997 (PYO97), 2000 (PYO2000) and 2014 (PYO2014). Based on next generation sequencing, de novo assembly and binning of contigs into draft genomes based on tetranucleotide distance, thirty and twenty-nine phage draft genomes were predicted in PYO97 and PYO2014, respectively. Of these, thirteen and fifteen shared high similarity to known phages. Eleven draft genomes were found to be common in the two cocktails. One of these showed no similarity to publicly available phage genomes. Representatives of phages targeting E. faecalis, E. faecium, E. coli, Proteus, P. aeruginosa and S. aureus were found in both cocktails. Finally, we estimated larger overlap of the PYO2000 cocktail to PYO97 compared to PYO2014. Using next generation sequencing and metagenomics analysis, we were able to characterize and compare the content of PYO cocktails separated by 17 years in time. Even though the cocktail composition is upgraded every six months, we found it to remain relatively stable over the years.
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spelling doaj.art-2678456ba507415a830921bf30624ff82022-12-21T19:53:08ZengMDPI AGViruses1999-49152017-11-0191132810.3390/v9110328v9110328Metagenomic Analysis of Therapeutic PYO Phage Cocktails from 1997 to 2014Julia Villarroel0Mette Voldby Larsen1Mogens Kilstrup2Morten Nielsen3Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, Building 208, 2800 Kongens Lyngby, DenmarkGoSeqIt ApS, Ved Klædebo 9, 2970 Hørsholm, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Matematiktorvet, Building 301, 2800 Kongens Lyngby, DenmarkDepartment of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, Building 208, 2800 Kongens Lyngby, DenmarkPhage therapy has regained interest in recent years due to the alarming spread of antibiotic resistance. Whilst phage cocktails are commonly sold in pharmacies in countries such as Georgia and Russia, this is not the case in western countries due to western regulatory agencies requiring a thorough characterization of the drug. Here, DNA sequencing of constituent biological entities constitutes a first step. The pyophage (PYO) cocktail is one of the main commercial products of the Georgian Eliava Institute of Bacteriophage, Microbiology and Virology and is used to cure skin infections. Since its first production in the 1930s, the composition of the cocktail has been periodically modified to add phages effective against emerging pathogenic strains. In this paper, we compared the composition of three PYO cocktails from 1997 (PYO97), 2000 (PYO2000) and 2014 (PYO2014). Based on next generation sequencing, de novo assembly and binning of contigs into draft genomes based on tetranucleotide distance, thirty and twenty-nine phage draft genomes were predicted in PYO97 and PYO2014, respectively. Of these, thirteen and fifteen shared high similarity to known phages. Eleven draft genomes were found to be common in the two cocktails. One of these showed no similarity to publicly available phage genomes. Representatives of phages targeting E. faecalis, E. faecium, E. coli, Proteus, P. aeruginosa and S. aureus were found in both cocktails. Finally, we estimated larger overlap of the PYO2000 cocktail to PYO97 compared to PYO2014. Using next generation sequencing and metagenomics analysis, we were able to characterize and compare the content of PYO cocktails separated by 17 years in time. Even though the cocktail composition is upgraded every six months, we found it to remain relatively stable over the years.https://www.mdpi.com/1999-4915/9/11/328PYO phage cocktailmetagenomicshuman phage therapy
spellingShingle Julia Villarroel
Mette Voldby Larsen
Mogens Kilstrup
Morten Nielsen
Metagenomic Analysis of Therapeutic PYO Phage Cocktails from 1997 to 2014
Viruses
PYO phage cocktail
metagenomics
human phage therapy
title Metagenomic Analysis of Therapeutic PYO Phage Cocktails from 1997 to 2014
title_full Metagenomic Analysis of Therapeutic PYO Phage Cocktails from 1997 to 2014
title_fullStr Metagenomic Analysis of Therapeutic PYO Phage Cocktails from 1997 to 2014
title_full_unstemmed Metagenomic Analysis of Therapeutic PYO Phage Cocktails from 1997 to 2014
title_short Metagenomic Analysis of Therapeutic PYO Phage Cocktails from 1997 to 2014
title_sort metagenomic analysis of therapeutic pyo phage cocktails from 1997 to 2014
topic PYO phage cocktail
metagenomics
human phage therapy
url https://www.mdpi.com/1999-4915/9/11/328
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AT mogenskilstrup metagenomicanalysisoftherapeuticpyophagecocktailsfrom1997to2014
AT mortennielsen metagenomicanalysisoftherapeuticpyophagecocktailsfrom1997to2014