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Computational transcriptomics and\n                    <jats:italic>Xenopus laevis<\/jats:italic>\n                    embryos are used to discover infection response pathways, identify potential tolerance inducer drugs, and validate their ability to induce broad tolerance.\n                    <jats:italic>Xenopus<\/jats:italic>\n                    exhibits natural tolerance to\n                    <jats:italic>Acinetobacter baumanii<\/jats:italic>\n                    ,\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    ,\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , and\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    bacteria, whereas\n                    <jats:italic>Aeromonas hydrophila<\/jats:italic>\n                    and\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    produce lethal infections. Transcriptional profiling leads to definition of a 20\u2010gene signature that discriminates between tolerant and susceptible states, as well as identification of a more active tolerance response to gram negative compared to gram positive bacteria. Gene pathways associated with active tolerance in\n                    <jats:italic>Xenopus<\/jats:italic>\n                    , including some involved in metal ion binding and hypoxia, are found to be conserved across species, including mammals, and administration of a metal chelator (deferoxamine) or a HIF\u20101\n                    <jats:italic>\u03b1<\/jats:italic>\n                    agonist (1,4\u2010DPCA) in embryos infected with lethal\n                    <jats:italic>A. hydrophila<\/jats:italic>\n                    increased survival despite high pathogen load. These data demonstrate the value of combining the\n                    <jats:italic>Xenopus<\/jats:italic>\n                    embryo infection model with computational multiomics analyses for mechanistic discovery and drug repurposing to induce host tolerance to bacterial infections.\n                  <\/jats:p>","DOI":"10.1002\/advs.202200222","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T01:41:04Z","timestamp":1655343664000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Enhancers of Host Immune Tolerance to Bacterial Infection Discovered Using Linked Computational and Experimental Approaches"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8310-5358","authenticated-orcid":false,"given":"Megan M.","family":"Sperry","sequence":"first","affiliation":[{"name":"Wyss Institute for Biologically Inspired Engineering at Harvard University  Boston MA 02115 USA"},{"name":"Department of Biology Tufts University  Medford MA 02155 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0485-4284","authenticated-orcid":false,"given":"Richard","family":"Novak","sequence":"additional","affiliation":[{"name":"Wyss Institute for Biologically Inspired Engineering at Harvard University  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vishal","family":"Keshari","sequence":"additional","affiliation":[{"name":"Wyss Institute for Biologically Inspired Engineering at Harvard University  Boston MA 02115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre L. 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