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The toxin causes a DNA damage response in human cells, characterised by cell\u2010cycle arrest and cellular distension, resulting in cellular senescence and increased bacterial burden. To better understand host responses to typhoid toxin, we performed a transcriptomic analysis of intoxicated host cells and found that the toxin induced expression of genes relating to the type\u2010I interferon response, including the ubiquitin\u2010like protein ISG15. ISG15 was upregulated in a STING\u2010dependent manner, reduced bacterial burden, and was found to be critical to host cell survival in response to the typhoid toxin and interferon. This highlights ISG15 as an important component of the host cell defence to the typhoid toxin.\n                  <\/jats:p>","DOI":"10.1111\/mmi.70067","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T18:55:51Z","timestamp":1776106551000},"page":"475-492","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Typhoid Toxin of\n                    <i>Salmonella enterica<\/i>\n                    Induces\n                    <scp>ISG15<\/scp>\n                    Responses Mediating Host Cell Survival and Counteracting Intracellular Infection"],"prefix":"10.1111","volume":"125","author":[{"given":"Daniel S.","family":"Stark","sequence":"first","affiliation":[{"name":"School of Biosciences University of Sheffield  Sheffield South Yorkshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"King","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Sheffield  Sheffield South Yorkshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela E. 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