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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.

Acute non-typhoidal salmonellosis (NTS) caused by a Gram-negative bacterium

Acute non-typhoidal salmonellosis (NTS) caused by Salmonella enterica Typhimurium (STM) is among the most prevalent of foodborne diseases. A global rising of antibiotic resistance strains of STM raises an urgent need for alternative methods to control this important pathogen. Major human food animals which harbor STM in their gut are cattle, swine, and poultry. Previous studies showed that the probiotic Limosilactobacillus (Lactobacillus) reuteri KUB-AC5 (AC5) exhibited anti-Salmonella activities in chicken by modulating gut microbiota and the immune response. However, the immunobiotic effect of AC5 in a mammalian host is still not known. Here, we investigated the anti-Salmonella and anti-inflammatory effects of AC5 on STM infection using a mouse colitis model. Three groups of C57BL/6 mice (prophylactic, therapeutic, and combined) were fed with 109 colony-forming units (cfu) AC5 daily for 7, 4, and 11 days, respectively. Then, the mice were challenged with STM compared to the untreated group. By using a specific primer pair, we found that AC5 can transiently colonize mouse gut (colon, cecum, and ileum). Interestingly, AC5 reduced STM gut proliferation and invasion together with attenuated gut inflammation and systemic dissemination in mice. The decreased STM numbers in mouse gut lumen, gut tissues, and spleen possibly came from longer AC5 feeding duration and/or the combinatorial (direct and indirect inhibitory) effect of AC5 on STM. However, AC5 attenuated inflammation (both in the gut and in the spleen) with no difference between these three approaches. This study demonstrated that AC5 confers both direct and indirect inhibitory effects on STM in the inflamed gut.