Therapeutic effects of oral administration of lytic Salmonella phages in a mouse model of non-typhoidal salmonellosis
Chutikarn Sukjoi, Songphon Buddhasiri, Arishabhas Tantibhadrasapa, Thattawan Kaewsakhorn, Preeda Phothaworn, Janet Y. Nale, Angela V. Lopez-Garcia, Manal AbuOun, Muna F. Anjum, Danish J. Malik, Edouard E. Galyov, Martha R. J. Clokie, Sunee Korbsrisate, Parameth Thiennimitr
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 (10 8 CFU/mouse) and treated with a single or a combination of ST-W77 and SE-W109 (10 10 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.