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 bacteriumSalmonella entericaserovar 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 ofSalmonellaphagesin vivois still poorly investigated.Salmonellaphages 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 reduceSalmonellainvasion 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 beforeS.Tm infection. Gentamicin protection assays demonstrated that ST-W77 and SE-W109 significantly reducedS.Tm invasion and inflammatory response in human colonocytes. Next, streptomycin-pretreated mice were orally infected withS.Tm (108CFU/mouse) and treated with a single or a combination of ST-W77 and SE-W109 (1010PFU/mouse for 4 days) by oral feeding. Our data showed that phage-treated mice had lowerS.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 thatSalmonellaphages ST-W77 and SE-W109 could be further developed as an alternative approach for treating an acute NTS in mammalian hosts.