TY - JOUR

T1 - Development of a Phage Cocktail to Target Salmonella Strains Associated with Swine

AU - Thanki, Anisha M.

AU - Clavijo, Viviana

AU - Healy, Kit

AU - Wilkinson, Rachael C.

AU - Sicheritz-Pontén, Thomas

AU - Millard, Andrew D.

AU - Clokie, Martha R. J.

PY - 2022

Y1 - 2022

N2 - Infections caused by multidrug resistant Salmonella 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 Salmonella 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. In vitro killing assays were conducted to determine the efficacy of phages alone and when combined, and three cocktails reduced bacterial numbers by ~2 x 10(3) 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, Salmonella 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 Salmonella colonisation in larvae, which supports their ability to similarly protect swine.

AB - Infections caused by multidrug resistant Salmonella 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 Salmonella 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. In vitro killing assays were conducted to determine the efficacy of phages alone and when combined, and three cocktails reduced bacterial numbers by ~2 x 10(3) 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, Salmonella 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 Salmonella colonisation in larvae, which supports their ability to similarly protect swine.

KW - Salmonella phages

KW - phage cocktails

KW - phage therapy

KW - phage characterisation

KW - larvae infection model

KW - single nucleotide polymorphisms

KW - BACTERIOPHAGE COCKTAIL

KW - LYTIC BACTERIOPHAGES

KW - MUTATION

KW - COLONIZATION

KW - FIBRONECTIN

KW - POPULATIONS

KW - PREDICTION

KW - RESISTANCE

KW - THERAPY

KW - DOMAINS

U2 - 10.3390/ph15010058

DO - 10.3390/ph15010058

M3 - Journal article

C2 - 35056115

VL - 15

JO - Pharmaceuticals

JF - Pharmaceuticals

SN - 1424-8247

IS - 1

M1 - 58

ER -