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To determine the<jats:italic>Y. pseudotuberculosis<\/jats:italic>factors important for growth during lung infection, we developed an intranasal model of infection in mice. Following intranasal inoculation, we monitored both bacterial growth in lungs and dissemination to systemic tissues. Intranasal inoculation with as few as 18 CFU of<jats:italic>Y. pseudotuberculosis<\/jats:italic>caused a lethal lung infection in some mice. Over the course of 7 days, wild-type<jats:italic>Y. pseudotuberculosis<\/jats:italic>replicated to nearly 1 \u00d7 10<jats:sup>8<\/jats:sup>CFU\/g of lung in BALB\/c mice, induced histopathology in lungs consistent with pneumonia, but disseminated sporadically to other tissues. In contrast, a \u0394<jats:italic>yopB<\/jats:italic>deletion strain was attenuated in this model, indicating that translocation of<jats:italic>Yersinia<\/jats:italic>outer proteins (Yops) is essential for virulence. Additionally, a \u0394<jats:italic>yopH<\/jats:italic>null mutant failed to grow to wild-type levels by 4 days postintranasal inoculation, but deletions of any other single effector YOP did not attenuate lung colonization 4 days postinfection. Strains with deletions in<jats:italic>yopH<\/jats:italic>and any one of the other known effector<jats:italic>yop<\/jats:italic>genes were more attenuated that the \u0394<jats:italic>yopH<\/jats:italic>strain, indicating a unique role for<jats:italic>yopH<\/jats:italic>in lungs. In summary, we have characterized the progression of a lung infection with an enteric<jats:italic>Yersinia<\/jats:italic>pathogen and shown that YopB and YopH are important in lung colonization and dissemination. Furthermore, this lung infection model with<jats:italic>Y. pseudotuberculosis<\/jats:italic>can be used to test potential therapeutics against<jats:italic>Yersinia<\/jats:italic>and other gram-negative infections in lungs.<\/jats:p>","DOI":"10.1128\/iai.01287-06","type":"journal-article","created":{"date-parts":[[2006,12,20]],"date-time":"2006-12-20T23:51:25Z","timestamp":1166658685000},"page":"429-442","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Intranasal Inoculation of Mice with<i>Yersinia pseudotuberculosis<\/i>Causes a Lethal Lung Infection That Is Dependent on<i>Yersinia<\/i>Outer Proteins andPhoP"],"prefix":"10.1128","volume":"75","author":[{"given":"Michael L.","family":"Fisher","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Biology, Tufts University, Boston, Massachusetts 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"Castillo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Biology, Tufts University, Boston, Massachusetts 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Mecsas","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Biology, Tufts University, Boston, Massachusetts 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.24.14043"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2405-2407.2004"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.11.7324-7331.2005"},{"key":"e_1_3_2_5_2","unstructured":"Balada J. 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