{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:11:36Z","timestamp":1790838696996,"version":"4.1.0"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Salmonella enterica<\/jats:italic> serovar Rissen (<jats:italic>S.<\/jats:italic> Rissen) is an emerging causative agent of foodborne diseases. The current emergence of antibiotic resistance makes necessary alternative therapeutic strategies. In this study, we investigated the potential of a phage-resistant strain of <jats:italic>S.<\/jats:italic> Rissen (R<jats:sup>R<\/jats:sup>) as a tool for developing an effective lipopolysaccharide (LPS)-based vaccine. The LPS O-antigen is known to play critical roles in protective immunity against <jats:italic>Salmonella<\/jats:italic>. However, the high toxicity of the LPS lipid A moiety limits its use in vaccines. Here, we demonstrated that the acquisition of bacteriophage resistance by <jats:italic>S.<\/jats:italic> Rissen leads to structural modifications in the LPS structure. Using NMR and mass spectrometry, we characterized the LPS from phage-resistant strains as a smooth variant bearing under-acylated Lipid A portions (penta- and tetra-acylated forms). We then combined RT-qPCR and NMR-based metabolomics to explore the effects of phage resistance and LPS modification on bacterial fitness and virulence. Finally, we conducted <jats:italic>in vivo<\/jats:italic> studies to determine whether lysogeny-induced remodeling of LPS affects the host immune response. Results revealed that the under-acylated variant of LPS from <jats:italic>R<jats:sup>R<\/jats:sup><\/jats:italic> attenuates the inflammatory response in BALB\/c mice, while eliciting a specific antibody response that protects against <jats:italic>S.<\/jats:italic> Rissen (R<jats:sup>W<\/jats:sup>) infection. In conclusion, our findings suggest that phage resistance, through lipid A modification, may offer a novel strategy for reducing LPS toxicity, highlighting its potential as a promising biological approach for developing LPS-based vaccines against <jats:italic>Salmonella<\/jats:italic> infections.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1450600","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T05:13:05Z","timestamp":1733893985000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Phage-resistance alters Lipid A reactogenicity: a new strategy for LPS-based conjugate vaccines against Salmonella Rissen"],"prefix":"10.3389","volume":"15","author":[{"given":"Paola","family":"Cuomo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Medaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Casillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gentile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Fruggiero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Michela","family":"Corsaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Capparelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1086\/650733","article-title":"International Collaboration on Enteric Disease \u201cBurden of Illness\u201d Studies. 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