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Bacterial factors required for food-borne infection of humans by<jats:italic>B. melitensis<\/jats:italic>are poorly understood. In this study, a mouse model of oral infection was characterized to assess the roles of urease, the VirB type IV secretion system, and lipopolysaccharide for establishing infection through the digestive tract.<jats:italic>B. melitensis<\/jats:italic>strain 16M was consistently recovered from the mesenteric lymph node (MLN), spleen, and liver beginning at 3 or 7 day postinfection (dpi). In the gut, persistence of the inoculum was observed up to 21 dpi. No inflammatory lesions were observed in the ileum or colon during infection. Mutant strains lacking the<jats:italic>ureABC<\/jats:italic>genes of the<jats:italic>ure1<\/jats:italic>operon,<jats:italic>virB2<\/jats:italic>, or<jats:italic>pmm<\/jats:italic>encoding phosphomannomutase were constructed and compared to the wild-type strain for infectivity through the digestive tract. Mutants lacking the<jats:italic>virB2<\/jats:italic>and<jats:italic>pmm<\/jats:italic>genes were attenuated in the spleen (<jats:italic>P<\/jats:italic>&lt; 0.05) and MLN (<jats:italic>P<\/jats:italic>&lt; 0.001), respectively. The wild-type and mutant strains had similar levels of resistance to low pH and 5 or 10% bile, suggesting that the reduced colonization of mutants was not the result of reduced resistance to acid pH or bile salts. In an in vitro lymphoepithelial cell (M-cell) model,<jats:italic>B. melitensis<\/jats:italic>transited rapidly through polarized enterocyte monolayers containing M-like cells; however, transit through monolayers containing only enterocytes was reduced or absent. These results indicate that<jats:italic>B. melitensis<\/jats:italic>is able to spread systemically from the digestive tract after infection, most likely through M cells of the mucosa-associated lymphoid tissue.<\/jats:p>","DOI":"10.1128\/iai.00417-09","type":"journal-article","created":{"date-parts":[[2009,8,4]],"date-time":"2009-08-04T16:07:37Z","timestamp":1249402057000},"page":"4197-4208","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":92,"title":["Establishment of Systemic<i>Brucella melitensis<\/i>Infection through the Digestive Tract Requires Urease, the Type IV Secretion System, and Lipopolysaccharide O Antigen"],"prefix":"10.1128","volume":"77","author":[{"given":"Tatiane A.","family":"Paixa\u0303o","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of California at Davis, Davis, California"},{"name":"Departamento de Clinica e Cirurgia Veterina\u0301ria, Escola de Veterina\u0301ria da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle M.","family":"Roux","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of California at Davis, Davis, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas B.","family":"den Hartigh","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of California at Davis, Davis, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumathi","family":"Sankaran-Walters","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of California at Davis, Davis, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satya","family":"Dandekar","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of California at Davis, Davis, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato L.","family":"Santos","sequence":"additional","affiliation":[{"name":"Departamento de Clinica e Cirurgia Veterina\u0301ria, Escola de Veterina\u0301ria da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene\u0301e M.","family":"Tsolis","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of California at Davis, Davis, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/030098588802500104"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.3.1008-1016.1998"},{"key":"e_1_3_2_4_2","unstructured":"Techniques for the brucellosis laboratory. 1988"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-7-57"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060905"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000631"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.12.8418-8424.2005"},{"key":"e_1_3_2_9_2","first-page":"115","volume":"93","year":"1984","unstructured":"Borriello, S. 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