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We recently identified a gene,<jats:italic>traJ<\/jats:italic>, which contributes to the ability of<jats:italic>E. coli<\/jats:italic>K1 to penetrate the blood-brain barrier in the neonatal rat. Because very little is known regarding the most critical step in disease progression, translocation to the gut and dissemination to the lymphoid tissues after a natural route of infection, we assessed the ability of a<jats:italic>traJ<\/jats:italic>mutant to cause systemic disease in the neonatal rat. Our studies determined that the<jats:italic>traJ<\/jats:italic>mutant is significantly less virulent than the wild type in the neonatal rat due to a decreased ability to disseminate from the mesenteric lymph nodes to the deeper tissues of the liver and spleen and to the blood during the early stages of systemic disease. Histopathologic studies determined that although significantly less or no mutant bacteria were recovered from the spleen and livers of infected neonatal rats, the inflammatory response was considerably greater than that in wild-type-colonized tissues. In vitro studies revealed that macrophages internalize the<jats:italic>traJ<\/jats:italic>mutant less frequently than they do the wild type and by a morphologically distinct process. Furthermore, we determined that tissue macrophages and dendritic cells within the liver and spleen are the major cellular targets of<jats:italic>E. coli<\/jats:italic>K1 and that TraJ significantly contributes to the predominantly intracellular nature of<jats:italic>E. coli<\/jats:italic>K1 within these professional phagocytes exclusively during the early stages of systemic disease. These data indicate that, contrary to earlier indications,<jats:italic>E. coli<\/jats:italic>K1 resides within professional phagocytes, and this is essential for the efficient progression of systemic disease.<\/jats:p>","DOI":"10.1128\/iai.72.1.478-488.2004","type":"journal-article","created":{"date-parts":[[2003,12,20]],"date-time":"2003-12-20T02:48:22Z","timestamp":1071888502000},"page":"478-488","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["TraJ-Dependent<i>Escherichia coli<\/i>K1 Interactions with Professional Phagocytes Are Important for Early Systemic Dissemination of Infection in the Neonatal Rat"],"prefix":"10.1128","volume":"72","author":[{"given":"Val T.","family":"Hill","sequence":"first","affiliation":[{"name":"Department of Pathology, Childrens Hospital Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy M.","family":"Townsend","sequence":"additional","affiliation":[{"name":"Department of Pathology, Childrens Hospital Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn S.","family":"Arias","sequence":"additional","affiliation":[{"name":"Department of Pathology, Childrens Hospital Los Angeles"},{"name":"University of Southern California School of Medicine, Los Angeles, California 90027"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine M.","family":"Jenabi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Childrens Hospital Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Gomez-Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Pathology, Childrens Hospital Los Angeles"},{"name":"University of Southern California School of Medicine, Los Angeles, California 90027"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Pathology, Childrens Hospital Los Angeles"},{"name":"University of Southern California School of Medicine, Los Angeles, California 90027"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie L.","family":"Badger","sequence":"additional","affiliation":[{"name":"Department of Pathology, Childrens Hospital Los Angeles"},{"name":"University of Southern California School of Medicine, Los Angeles, California 90027"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.593"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00202554"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-200106000-00005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.12.5692-5697.1998"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01840.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.9.5056-5061.2000"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.58.1.275-278.1990"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1992.tb01518.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.57.7.2141-2148.1989"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.25.1.293-298.1979"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.22.2.480-485.1978"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/154.3.497"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.990190412"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0095-5108(18)31224-7"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.58.2.162-210.1994"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.16.1.75-80.1977"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2001.tb10630.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/148.3.395"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.7.3566-3570.1999"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.11.4470-4475.1995"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"262","DOI":"10.4049\/jimmunol.110.1.262","volume":"110","year":"1973","unstructured":"Kasper, D. 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