{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:41:46Z","timestamp":1789008106312,"version":"build-2803163510"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T00:00:00Z","timestamp":1267401600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Two mutant strains of<jats:italic>Yersinia pestis<\/jats:italic>KIM5+, a \u0394<jats:italic>crp<\/jats:italic>mutant and a mutant with arabinose-dependent regulated delayed-shutoff<jats:italic>crp<\/jats:italic>expression (<jats:italic>araC<\/jats:italic>P<jats:sub>BAD<\/jats:sub><jats:italic>crp<\/jats:italic>), were constructed, characterized<jats:italic>in vitro<\/jats:italic>, and evaluated for virulence, immunogenicity, and protective efficacy in mice. Both strains were highly attenuated by the subcutaneous (s.c.) route. The 50% lethal doses (LD<jats:sub>50<\/jats:sub>s) of the \u0394<jats:italic>crp<\/jats:italic>and<jats:italic>araC<\/jats:italic>P<jats:sub>BAD<\/jats:sub><jats:italic>crp<\/jats:italic>mutants were approximately 1,000,000-fold and 10,000-fold higher than those of<jats:italic>Y. pestis<\/jats:italic>KIM5+, respectively, indicating that both strains were highly attenuated. Mice vaccinated s.c. with 3.8 \u00d7 10<jats:sup>7<\/jats:sup>CFU of the \u0394<jats:italic>crp<\/jats:italic>mutant developed high anti-<jats:italic>Y. pestis<\/jats:italic>and anti-LcrV serum IgG titers, both with a strong Th2 bias, and induced protective immunity against subcutaneous challenge with virulent<jats:italic>Y. pestis<\/jats:italic>(80% survival) but no protection against pulmonary challenge. Mice vaccinated with 3.0 \u00d7 10<jats:sup>4<\/jats:sup>CFU of the<jats:italic>araC<\/jats:italic>P<jats:sub>BAD<\/jats:sub><jats:italic>crp<\/jats:italic>mutant also developed high anti-<jats:italic>Y. pestis<\/jats:italic>and anti-LcrV serum IgG titers but with a more balanced Th1\/Th2 response. This strain induced complete protection against s.c. challenge and partial protection (70% survival) against pulmonary challenge. Our results demonstrate that arabinose-dependent regulated<jats:italic>crp<\/jats:italic>expression is an effective strategy to attenuate<jats:italic>Y. pestis<\/jats:italic>while retaining strong immunogenicity, leading to protection against the pneumonic and bubonic forms of plague.<\/jats:p>","DOI":"10.1128\/iai.01122-09","type":"journal-article","created":{"date-parts":[[2010,1,20]],"date-time":"2010-01-20T04:52:47Z","timestamp":1263963167000},"page":"1304-1313","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["<i>Yersinia pestis<\/i>with Regulated Delayed Attenuation as a Vaccine Candidate To Induce Protective Immunity against Plague"],"prefix":"10.1128","volume":"78","author":[{"given":"Wei","family":"Sun","sequence":"first","affiliation":[{"name":"Center for Infectious Disease and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L.","family":"Roland","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Kuang","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine G.","family":"Branger","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Roy","family":"Curtiss","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01244.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.12.057"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-72124-8_36"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.7.3673-3681.2003"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/5.4.748"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200205077"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.62.4.1315-1352.1998"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00699-08"},{"key":"e_1_3_2_10_2","unstructured":"Regulated bacterial lysis for gene vaccine vector delivery and antigen release. 2006"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.55.12.3035-3043.1987"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00693-08"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120163297"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01157-08"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.145.1.620-623.1981"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/21.Supplement_2.S178"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.5.2829-2837.2001"},{"key":"e_1_3_2_18_2","first-page":"503","volume":"4","year":"2003","unstructured":"Gor, D. 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