Therapeutic effects of oral administration of lytic Salmonella phages in a mouse model of non-typhoidal salmonellosis

Abstract

Acute non-typhoidal salmonellosis (NTS) caused by a Gram-negative bacterium Salmonella enterica serovar Typhimurium (S. Tm) is one of the most common bacterial foodborne diseases worldwide. Bacteriophages (phages) can specifically target and lyse their host bacteria, including the multidrug-resistant strains, without collateral damage to other bacteria in the community. However, the therapeutic use of Salmonella phages in vivo is still poorly investigated. Salmonella phages ST-W77 and SE-W109 have previously been shown by our group to be useful for biocontrol properties. Here, we tested whether phages ST-W77 and SE-W109 can reduce Salmonella invasion into cultured human cells and confer a therapeutic benefit for acute NTS in a mammalian host. Human colonocytes, T84 cells, were treated with phages ST-W77, SE-W109, and its combination for 5 min before S. Tm infection. Gentamicin protection assays demonstrated that ST-W77 and SE-W109 significantly reduced S. Tm invasion and inflammatory response in human colonocytes. Next, streptomycin-pretreated mice were orally infected with S. Tm (108 CFU/mouse) and treated with a single or a combination of ST-W77 and SE-W109 (1010 PFU/mouse for 4 days) by oral feeding. Our data showed that phage-treated mice had lower S. Tm numbers and tissue inflammation compared to the untreated mice. Our study also revealed that ST-W77 and SE-W109 persist in the mouse gut lumen, but not in systemic sites. Together, these data suggested that Salmonella phages ST-W77 and SE-W109 could be further developed as an alternative approach for treating an acute NTS in mammalian hosts.

Pathogen genomics and phage-based solutions for accurately identifying and controlling Salmonella pathogens

“…The outer ring shows the annotated genes, with 100% identity (solid brown), as well as low (light brown or grey) or no sequence identity (gaps). (Nale et al, 2021) and mice (Sukjoi et al, 2022), as well as in ex vivo analyses in avian, porcine, and human epithelial cell cultures (Nale et al, 2023); therefore, their use on poultry farms as biocontrols is likely to be the next step. Unfortunately, no phage tested in this study completely lysed the S. Kentucky ST198 MDR clones; therefore, further study is needed.…”

“…Twenty-two Salmonella phages, the biological properties of which have been extensively reported (Phothaworn et al, 2020;Nale et al, 2021;Sukjoi et al, 2022;Nale et al, 2023), were tested. Twenty (SPFM9, SPFM11, SPFM17, SPFM4, SPFM2, SPFM19, SPFM14, SPFM10, SPFM12, SPFM13, SPFM20, SPFM1, SPFM3, SPFM16, SPFM15, SPFM7, SPFM6, SPFM8, SPFM21, and SPFM5) were previously isolated and characterized in a UK laboratory, while two (STW-77 and SEW-109) were previously isolated and characterized in Thailand (Thanki et al, 2019;Phothaworn et al, 2020;Nale et al, 2021).…”