AUTHOR=Sukjoi Chutikarn , Buddhasiri Songphon , Tantibhadrasapa Arishabhas , Kaewsakhorn Thattawan , Phothaworn Preeda , Nale Janet Y. , Lopez-Garcia Angela V. , AbuOun Manal , Anjum Muna F. , Malik Danish J. , Galyov Edouard E. , Clokie Martha R. J. , Korbsrisate Sunee , Thiennimitr Parameth 

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

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.955136

DOI=10.3389/fmicb.2022.955136

ISSN=1664-302X

ABSTRACT=<p>Acute non-typhoidal salmonellosis (NTS) caused by a Gram-negative bacterium <italic>Salmonella enterica</italic> serovar Typhimurium (<italic>S.</italic> 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 <italic>Salmonella</italic> phages <italic>in vivo</italic> is still poorly investigated. <italic>Salmonella</italic> 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 <italic>Salmonella</italic> 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 <italic>S.</italic> Tm infection. Gentamicin protection assays demonstrated that ST-W77 and SE-W109 significantly reduced <italic>S.</italic> Tm invasion and inflammatory response in human colonocytes. Next, streptomycin-pretreated mice were orally infected with <italic>S.</italic> Tm (10<sup>8</sup> CFU/mouse) and treated with a single or a combination of ST-W77 and SE-W109 (10<sup>10</sup> PFU/mouse for 4 days) by oral feeding. Our data showed that phage-treated mice had lower <italic>S.</italic> 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 <italic>Salmonella</italic> phages ST-W77 and SE-W109 could be further developed as an alternative approach for treating an acute NTS in mammalian hosts.</p>