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Our previous observations also indicated that strain \u03c710015(pCD1Ap) (\u0394<jats:italic>lpxP32<\/jats:italic>::P<jats:sub>lpxL<\/jats:sub><jats:italic>lpxL<\/jats:italic>) stimulated a strong inflammatory reaction but sickened mice before recovery and retained virulence via intranasal (i.n.) infection. The development of live, attenuated<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Y. pestis<\/jats:named-content>vaccines may be facilitated by detoxification of its lipopolysaccharide (LPS). Heterologous expression of the lipid A 1-phosphatase, LpxE, from<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Francisella tularensis<\/jats:named-content>in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Y. pestis<\/jats:named-content>yields predominantly 1-dephosphorylated lipid A, as confirmed by mass spectrometry. Results indicated that expression of LpxE on top of LpxL provided no significant reduction in virulence of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Y. pestis<\/jats:named-content>in mice when it was administered i.n. but actually reduced the 50% lethal dose (LD<jats:sub>50<\/jats:sub>) by 3 orders of magnitude when the strain was administered subcutaneously (s.c.). Additionally, LpxE synthesis in wild-type<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Y. pestis<\/jats:named-content>KIM6+(pCD1Ap) led to slight attenuation by s.c. inoculation but no virulence change by i.n. inoculation in mice. In contrast to<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Salmonella enterica<\/jats:named-content>, expression of LpxE does not attenuate the virulence of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Y. pestis<\/jats:named-content>.<\/jats:p>","DOI":"10.1128\/iai.01403-12","type":"journal-article","created":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T02:27:29Z","timestamp":1359426449000},"page":"1172-1185","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Pathogenicity of Yersinia pestis Synthesis of 1-Dephosphorylated Lipid A"],"prefix":"10.1128","volume":"81","author":[{"given":"Wei","family":"Sun","sequence":"first","affiliation":[{"name":"Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Six","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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