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

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posted on 2023-05-26, 15:03 authored by C Sukjoi, S Buddhasiri, A Tantibhadrasapa, T Kaewsakhorn, P Phothaworn, JY Nale, AV Lopez-Garcia, M AbuOun, MF Anjum, DJ Malik, EE Galyov, MRJ Clokie, S Korbsrisate, P Thiennimitr
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.

Funding

This work was funded by Biotechnology and Biological Sciences Research Council (BBSRC), grant number RM38G0140 awarded to MC, and the National Science and Technology Development Agency (NSTDA), grant number P-18-50454 awarded to SK, the Faculty of Medicine Research Fund (MIC-2561-05411), Chiang Mai University, Chiang Mai, Thailand and the Thailand Research Fund (RGNS 63-066) awarded to PT. CS was awarded by the Faculty of Medicine Chiang Mai University graduate student scholarship. AT was awarded by the Chiang Mai University (CMU) Presidential scholarship.

History

Citation

Sukjoi C, Buddhasiri S, Tantibhadrasapa A, Kaewsakhorn T, Phothaworn P, Nale JY, Lopez-Garcia AV, AbuOun M, Anjum MF, Malik DJ, Galyov EE, Clokie MRJ, Korbsrisate S and Thiennimitr P (2022) Therapeutic effects of oral administration of lytic Salmonella phages in a mouse model of non-typhoidal salmonellosis. Front. Microbiol. 13:955136. doi: 10.3389/fmicb.2022.955136

Author affiliation

Department of Genetics and Genome Biology

Version

  • VoR (Version of Record)

Published in

Frontiers in Microbiology

Volume

13

Pagination

955136

Publisher

Frontiers Media SA

issn

1664-302X

eissn

1664-302X

Acceptance date

2022-05-28

Copyright date

2022

Available date

2023-05-26

Language

eng

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