Development of a Phage Cocktail to Target <i>Salmonella</i> Strains Associated with Swine

Infections caused by multidrug resistant <i>Salmonella</i> strains are problematic in swine and are entering human food chains. Bacteriophages (phages) could be used to complement or replace antibiotics to reduce infection within swine. Here, we extensively characterised six broad host r...

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Main Authors: Anisha M. Thanki, Viviana Clavijo, Kit Healy, Rachael C. Wilkinson, Thomas Sicheritz-Pontén, Andrew D. Millard, Martha R. J. Clokie
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/15/1/58
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author Anisha M. Thanki
Viviana Clavijo
Kit Healy
Rachael C. Wilkinson
Thomas Sicheritz-Pontén
Andrew D. Millard
Martha R. J. Clokie
author_facet Anisha M. Thanki
Viviana Clavijo
Kit Healy
Rachael C. Wilkinson
Thomas Sicheritz-Pontén
Andrew D. Millard
Martha R. J. Clokie
author_sort Anisha M. Thanki
collection DOAJ
description Infections caused by multidrug resistant <i>Salmonella</i> strains are problematic in swine and are entering human food chains. Bacteriophages (phages) could be used to complement or replace antibiotics to reduce infection within swine. Here, we extensively characterised six broad host range lytic <i>Salmonella</i> phages, with the aim of developing a phage cocktail to prevent or treat infection. Intriguingly, the phages tested differed by one to five single nucleotide polymorphisms. However, there were clear phenotypic differences between them, especially in their heat and pH sensitivity. <i>In vitro</i> killing assays were conducted to determine the efficacy of phages alone and when combined, and three cocktails reduced bacterial numbers by ~2 × 10<sup>3</sup> CFU/mL within two hours. These cocktails were tested in larvae challenge studies, and prophylactic treatment with phage cocktail SPFM10-SPFM14 was the most efficient. Phage treatment improved larvae survival to 90% after 72 h versus 3% in the infected untreated group. In 65% of the phage-treated larvae, <i>Salmonella</i> counts were below the detection limit, whereas it was isolated from 100% of the infected, untreated larvae group. This study demonstrates that phages effectively reduce <i>Salmonella</i> colonisation in larvae, which supports their ability to similarly protect swine.
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spelling doaj.art-bfa632b1e2f7406e8120b412fa52d57a2023-11-23T15:01:26ZengMDPI AGPharmaceuticals1424-82472022-01-011515810.3390/ph15010058Development of a Phage Cocktail to Target <i>Salmonella</i> Strains Associated with SwineAnisha M. Thanki0Viviana Clavijo1Kit Healy2Rachael C. Wilkinson3Thomas Sicheritz-Pontén4Andrew D. Millard5Martha R. J. Clokie6Department of Genetics and Genome Biology, College of Life Sciences, University of Leicester, Leicester LE1 7RH, UKDepartment of Biological Sciences, Universidad de los Andes, Bogota 111711, ColombiaDepartment of Genetics and Genome Biology, College of Life Sciences, University of Leicester, Leicester LE1 7RH, UKSwansea University Medical School, Swansea University, Swansea SA2 8PP, UKSection for Evolutionary Genomics, The GLOBE Institute, University of Copenhagen, 1353 Copenhagen, DenmarkDepartment of Genetics and Genome Biology, College of Life Sciences, University of Leicester, Leicester LE1 7RH, UKDepartment of Genetics and Genome Biology, College of Life Sciences, University of Leicester, Leicester LE1 7RH, UKInfections caused by multidrug resistant <i>Salmonella</i> strains are problematic in swine and are entering human food chains. Bacteriophages (phages) could be used to complement or replace antibiotics to reduce infection within swine. Here, we extensively characterised six broad host range lytic <i>Salmonella</i> phages, with the aim of developing a phage cocktail to prevent or treat infection. Intriguingly, the phages tested differed by one to five single nucleotide polymorphisms. However, there were clear phenotypic differences between them, especially in their heat and pH sensitivity. <i>In vitro</i> killing assays were conducted to determine the efficacy of phages alone and when combined, and three cocktails reduced bacterial numbers by ~2 × 10<sup>3</sup> CFU/mL within two hours. These cocktails were tested in larvae challenge studies, and prophylactic treatment with phage cocktail SPFM10-SPFM14 was the most efficient. Phage treatment improved larvae survival to 90% after 72 h versus 3% in the infected untreated group. In 65% of the phage-treated larvae, <i>Salmonella</i> counts were below the detection limit, whereas it was isolated from 100% of the infected, untreated larvae group. This study demonstrates that phages effectively reduce <i>Salmonella</i> colonisation in larvae, which supports their ability to similarly protect swine.https://www.mdpi.com/1424-8247/15/1/58<i>Salmonella</i> phagesphage cocktailsphage therapyphage characterisationlarvae infection modelsingle nucleotide polymorphisms
spellingShingle Anisha M. Thanki
Viviana Clavijo
Kit Healy
Rachael C. Wilkinson
Thomas Sicheritz-Pontén
Andrew D. Millard
Martha R. J. Clokie
Development of a Phage Cocktail to Target <i>Salmonella</i> Strains Associated with Swine
Pharmaceuticals
<i>Salmonella</i> phages
phage cocktails
phage therapy
phage characterisation
larvae infection model
single nucleotide polymorphisms
title Development of a Phage Cocktail to Target <i>Salmonella</i> Strains Associated with Swine
title_full Development of a Phage Cocktail to Target <i>Salmonella</i> Strains Associated with Swine
title_fullStr Development of a Phage Cocktail to Target <i>Salmonella</i> Strains Associated with Swine
title_full_unstemmed Development of a Phage Cocktail to Target <i>Salmonella</i> Strains Associated with Swine
title_short Development of a Phage Cocktail to Target <i>Salmonella</i> Strains Associated with Swine
title_sort development of a phage cocktail to target i salmonella i strains associated with swine
topic <i>Salmonella</i> phages
phage cocktails
phage therapy
phage characterisation
larvae infection model
single nucleotide polymorphisms
url https://www.mdpi.com/1424-8247/15/1/58
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