{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:32:37Z","timestamp":1792373557939,"version":"4.4.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,7,8]]},"abstract":"<jats:p>\n                    We have devised and constructed a biological containment system designed to cause programmed bacterial cell lysis with no survivors. We have validated this system, using\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    serovar Typhimurium vaccines for antigen delivery after colonization of host lymphoid tissues. The system is composed of two parts. The first component is\n                    <jats:italic>Salmonella typhimurium<\/jats:italic>\n                    strain \u03c78937, with deletions of\n                    <jats:italic>asdA<\/jats:italic>\n                    and arabinose-regulated expression of\n                    <jats:italic>murA<\/jats:italic>\n                    , two genes required for peptidoglycan synthesis and additional mutations to enhance complete lysis and antigen delivery. The second component is plasmid pYA3681, which encodes arabinose-regulated\n                    <jats:italic>murA<\/jats:italic>\n                    and\n                    <jats:italic>asdA<\/jats:italic>\n                    expression and C2-regulated synthesis of antisense\n                    <jats:italic>asdA<\/jats:italic>\n                    and\n                    <jats:italic>murA<\/jats:italic>\n                    mRNA transcribed from the P22 P\n                    <jats:sub>R<\/jats:sub>\n                    promoter. An arabinose-regulated\n                    <jats:italic>c2<\/jats:italic>\n                    gene is present in the chromosome. \u03c78937(pYA3681) exhibits arabinose-dependent growth. Upon invasion of host tissues, an arabinose-free environment, transcription of\n                    <jats:italic>asdA<\/jats:italic>\n                    ,\n                    <jats:italic>murA<\/jats:italic>\n                    , and\n                    <jats:italic>c2<\/jats:italic>\n                    ceases, and concentrations of their gene products decrease because of cell division. The drop in C2 concentration results in activation of P\n                    <jats:sub>R<\/jats:sub>\n                    , driving synthesis of antisense mRNA to block translation of any residual\n                    <jats:italic>asdA<\/jats:italic>\n                    and\n                    <jats:italic>murA<\/jats:italic>\n                    mRNA. A highly antigenic \u03b1-helical domain of\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    Rx1 PspA was cloned into pYA3681, resulting in pYA3685 to test antigen delivery. Mice orally immunized with \u03c78937(pYA3685) developed antibody responses to PspA and\n                    <jats:italic>Salmonella<\/jats:italic>\n                    outer membrane proteins. No viable vaccine strain cells were detected in host tissues after 21 days. This system has potential applications with other Gram-negative bacteria in which biological containment would be desirable.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0803801105","type":"journal-article","created":{"date-parts":[[2008,7,7]],"date-time":"2008-07-07T21:09:32Z","timestamp":1215464972000},"page":"9361-9366","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":134,"title":["Regulated programmed lysis of recombinant\n                    <i>Salmonella<\/i>\n                    in host tissues to release protective antigens and confer biological containment"],"prefix":"10.1073","volume":"105","author":[{"given":"Wei","family":"Kong","sequence":"first","affiliation":[{"name":"*Center for Infectious Diseases and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ 85287-5401;"},{"name":"Department of Biology, Washington University, St. Louis, MO 63130; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Young","family":"Wanda","sequence":"additional","affiliation":[{"name":"*Center for Infectious Diseases and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ 85287-5401;"},{"name":"Department of Biology, Washington University, St. Louis, MO 63130; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biology, Washington University, St. Louis, MO 63130; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Bollen","sequence":"additional","affiliation":[{"name":"Department of Biology, Washington University, St. Louis, MO 63130; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Tinge","sequence":"additional","affiliation":[{"name":"Megan Health, Inc., 3655 Vista Avenue, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L.","family":"Roland","sequence":"additional","affiliation":[{"name":"*Center for Infectious Diseases and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ 85287-5401;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Roy","family":"Curtiss","sequence":"additional","affiliation":[{"name":"*Center for Infectious Diseases and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ 85287-5401;"},{"name":"Department of Biology, Washington University, St. Louis, MO 63130; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,7,8]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.5.3.328"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012491543-5\/50060-7"},{"key":"e_1_3_3_3_2","first-page":"693","article-title":"Construction of an Asd+ expression-cloning vector: Stable maintenance and high level expression of cloned genes in a Salmonella vaccine strain","volume":"6","author":"Nakayama K","year":"1988","unstructured":"K Nakayama, SM Kelly, R Curtiss, Construction of an Asd+ expression-cloning vector: Stable maintenance and high level expression of cloned genes in a Salmonella vaccine strain. 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