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Here, we show that\n                    <jats:italic>S.<\/jats:italic>\n                    Typhi can replicate in vivo in nonobese diabetic (NOD)-\n                    <jats:italic>\n                      scid IL2r\u03b3\n                      <jats:sup>null<\/jats:sup>\n                    <\/jats:italic>\n                    mice engrafted with human hematopoietic stem cells (hu-SRC-SCID mice) to cause a lethal infection with pathological and inflammatory cytokine responses resembling human typhoid. In contrast,\n                    <jats:italic>S.<\/jats:italic>\n                    Typhi does not exhibit net replication or cause illness in nonengrafted or immunocompetent control animals. Screening of transposon pools in hu-SRC-SCID mice revealed both known and previously unknown\n                    <jats:italic>Salmonella<\/jats:italic>\n                    virulence determinants, including\n                    <jats:italic>Salmonella<\/jats:italic>\n                    Pathogenicity Islands 1, 2, 3, 4, and 6. Our observations indicate that the presence of human immune cells allows the in vivo replication of\n                    <jats:italic>S.<\/jats:italic>\n                    Typhi in mice. The hu-SRC-SCID mouse provides an unprecedented opportunity to gain insights into\n                    <jats:italic>S.<\/jats:italic>\n                    Typhi pathogenesis and devise strategies for the prevention of typhoid fever.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1005566107","type":"journal-article","created":{"date-parts":[[2010,8,17]],"date-time":"2010-08-17T00:40:39Z","timestamp":1282005639000},"page":"15589-15594","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":123,"title":["Humanized nonobese diabetic-\n                    <i>\n                      scid IL2r\u03b3\n                      <sup>null<\/sup>\n                    <\/i>\n                    mice are susceptible to lethal\n                    <i>Salmonella<\/i>\n                    Typhi infection"],"prefix":"10.1073","volume":"107","author":[{"given":"Stephen J.","family":"Libby","sequence":"first","affiliation":[{"name":"Departments of Laboratory Medicine and Microbiology, University of Washington School of Medicine, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Brehm","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pathology, University of Massachusetts Medical School, Worcester, MA 01605;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale L.","family":"Greiner","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pathology, University of Massachusetts Medical School, Worcester, MA 01605;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard D.","family":"Shultz","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"McClelland","sequence":"additional","affiliation":[{"name":"Vaccine Research Institute of San Diego, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine and Microbiology, University of Washington School of Medicine, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad T.","family":"Cookson","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine and Microbiology, University of Washington School of Medicine, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce E.","family":"Karlinsey","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine and Microbiology, University of Washington School of Medicine, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Traci L.","family":"Kinkel","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine and Microbiology, University of Washington School of Medicine, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Porwollik","sequence":"additional","affiliation":[{"name":"Vaccine Research Institute of San Diego, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocio","family":"Canals","sequence":"additional","affiliation":[{"name":"Vaccine Research Institute of San Diego, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Cummings","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine and Microbiology, University of Washington School of Medicine, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferric C.","family":"Fang","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine and Microbiology, University of Washington School of Medicine, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,8,16]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"957","article-title":"Vaccination against typhoid fever: Present status","volume":"72","author":"Ivanoff B","year":"1994","unstructured":"B Ivanoff, MM Levine, PH Lambert, Vaccination against typhoid fever: Present status. 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