Pathogen genomics and phage-based solutions to accurately identify and control Salmonella dissemination in poultry flocks.

Salmonella is a food-borne pathogen that causes gastrointestinal infections in humans. Prevalent serotypes are linked to poultry sources, and many strains are multidrug resistant. To gain insight into the genomic diversity of the serotypes and their potential contribution to disease, here, we characterised the virulence factors and antimicrobial resistance genes encoded in 143 UK and Thai poultry isolates. To augment current control methods, we determined the sensitivity of the isolates to twenty-two previously characterised Salmonella phages. Of the 17 serovars identified, S. Typhimurium and its sero-variants emerged as the most prevalent, and phylogenetic analysis indicated that these isolates are characteristic of their country and source. Resistance to sulfamethoxazole and ciprofloxacin was highest in isolates from the United Kingdom and Thailand, respectively, and 17-18% of all isolates were multidrug resistant (MDR). Several virulence genes were correlated with MDR isolates from a specific serovar and country. In-depth genomic analyses using long-read sequencing of isolates from three representative serovars revealed the presence of global epidemic clones, indicating they are widespread in poultry. The clones included the MDR ST198 S. Kentucky, harbouring a Salmonella Genomic Island-1 (SGI)-K; the European ST34 S. 1,4,[5],12:i:- harbouring SGI-4 and mercury-resistance genes; and an isolate harbouring a MDR-plasmid identified in the S. 1,4,12:i:- Spanish clone. The isolates showed variable sensitivity to phages using the spot testing technique. Among the phages examined, STW-77 was found to be the most effective, lysing on 37.76% of the isolates, including clinically important serovars: S. Enteritidis (80.95%), S. Typhimurium (66.67%), S. 1,4,[5],12:i:- (83.3%), and S. 1,4,12:i:- (71.43%). The S. 1,4,12:i:- isolate harbouring the MDR plasmid was lysed by STW-77 and SEW-109. Our data revealed that combining genomics and phage sensitivity assays can provide powerful tools which hold promise of accurately identifying and providing bio-controls for preventing the dissemination of Salmonella in poultry flocks.