{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T02:43:26Z","timestamp":1768272206873,"version":"3.49.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T00:00:00Z","timestamp":1346457600000},"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":[[2012,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia pseudomallei<\/jats:named-content>\n            is a Gram-negative soil bacterium and the causative agent of melioidosis, a disease of humans and animals. It is also listed as a category B bioterrorism threat agent by the U.S. Centers for Disease Control and Prevention, and there is currently no melioidosis vaccine available. Small modified nucleotides such as the hyperphosphorylated guanosine molecules ppGpp and pppGpp play an important role as signaling molecules in prokaryotes. They mediate a global stress response under starvation conditions and have been implicated in the regulation of virulence and survival factors in many bacterial species. In this study, we created a\n            <jats:italic>relA spoT<\/jats:italic>\n            double mutant in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. pseudomallei<\/jats:named-content>\n            strain K96243, which lacks (p)ppGpp-synthesizing enzymes, and investigated its phenotype\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            . The\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. pseudomallei<\/jats:named-content>\n            \u0394\n            <jats:italic>relA<\/jats:italic>\n            \u0394\n            <jats:italic>spoT<\/jats:italic>\n            mutant displayed a defect in stationary-phase survival and intracellular replication in murine macrophages. Moreover, the mutant was attenuated in the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Galleria mellonella<\/jats:named-content>\n            insect model and in both acute and chronic mouse models of melioidosis. Vaccination of mice with the \u0394\n            <jats:italic>relA<\/jats:italic>\n            \u0394\n            <jats:italic>spoT<\/jats:italic>\n            mutant resulted in partial protection against infection with wild-type\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. pseudomallei<\/jats:named-content>\n            . In summary, (p)ppGpp signaling appears to represent an essential component of the regulatory network governing virulence gene expression and stress adaptation in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. pseudomallei<\/jats:named-content>\n            , and the \u0394\n            <jats:italic>relA<\/jats:italic>\n            \u0394\n            <jats:italic>spoT<\/jats:italic>\n            mutant may be a promising live-attenuated vaccine candidate.\n          <\/jats:p>","DOI":"10.1128\/iai.00178-12","type":"journal-article","created":{"date-parts":[[2012,7,10]],"date-time":"2012-07-10T15:23:37Z","timestamp":1341933817000},"page":"3247-3255","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Role of RelA and SpoT in Burkholderia pseudomallei Virulence and Immunity"],"prefix":"10.1128","volume":"80","author":[{"given":"Claudia M.","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"College of Life and Environmental Sciences, Biosciences, University of Exeter, Exeter, Devon, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Conejero","sequence":"additional","affiliation":[{"name":"London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha","family":"Spink","sequence":"additional","affiliation":[{"name":"London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew E.","family":"Wand","sequence":"additional","affiliation":[{"name":"College of Life and Environmental Sciences, Biosciences, University of Exeter, Exeter, Devon, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory J.","family":"Bancroft","sequence":"additional","affiliation":[{"name":"London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard W.","family":"Titball","sequence":"additional","affiliation":[{"name":"College of Life and Environmental Sciences, Biosciences, University of Exeter, Exeter, Devon, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06115.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-51-7-539"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.9.5290-5294.2002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023479"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2005.11.006"},{"key":"e_1_3_2_7_2","first-page":"1458","volume-title":"Escherichia coli and Salmonella: cellular and molecular biology","author":"Cashel M","year":"1996","unstructured":"CashelMGentryDHernandezVJVinellaD. 1996. 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