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Here we present evidence to demonstrate that the<jats:italic>smpB-ssrA<\/jats:italic>genes are required for pathogenesis of<jats:italic>Yersinia pestis<\/jats:italic>, the causative agent of plague. We found that disruption of the<jats:italic>smpB-ssrA<\/jats:italic>genes leads to reduction in secretion of the type III secretion-related proteins YopB, YopD, and LcrV, which are essential for virulence. Consistent with these observations, the<jats:italic>smpB-ssrA<\/jats:italic>mutant of<jats:italic>Y. pestis<\/jats:italic>was severely attenuated in a mouse model of infection via both the intranasal and intravenous routes. Most significantly, intranasal vaccination of mice with the<jats:italic>smpB-ssrA<\/jats:italic>mutant strain of<jats:italic>Y. pestis<\/jats:italic>induced a strong antibody response. The vaccinated animals were well protected against subsequent lethal intranasal challenges with virulent<jats:italic>Y. pestis<\/jats:italic>. Taken together, our results indicate that the<jats:italic>smpB-ssrA<\/jats:italic>mutant of<jats:italic>Y. pestis<\/jats:italic>possesses the desired qualities for a live attenuated cell-based vaccine against pneumonic plague.<\/jats:p>","DOI":"10.1128\/iai.00976-09","type":"journal-article","created":{"date-parts":[[2010,1,12]],"date-time":"2010-01-12T02:44:53Z","timestamp":1263264293000},"page":"1284-1293","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["The<i>smpB-ssrA<\/i>Mutant of<i>Yersinia pestis<\/i>Functions as a Live Attenuated Vaccine To Protect Mice against Pulmonary Plague Infection"],"prefix":"10.1128","volume":"78","author":[{"given":"Nihal A.","family":"Okan","sequence":"first","affiliation":[{"name":"Center for Infectious Diseases and Department of Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio","family":"Mena","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Department of Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge L.","family":"Benach","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Department of Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Bliska","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Department of Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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