{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T21:18:56Z","timestamp":1789852736548,"version":"4.0.1"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI073558"],"award-info":[{"award-number":["R01 AI073558"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI116453"],"award-info":[{"award-number":["R01 AI116453"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["F31 AI115931"],"award-info":[{"award-number":["F31 AI115931"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006031","name":"United States-Israel Binational Agricultural Research and Development Fund","doi-asserted-by":"publisher","award":["US-4378-11"],"award-info":[{"award-number":["US-4378-11"]}],"id":[{"id":"10.13039\/100006031","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>\n            species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how\n            <jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>\n            spp. succeed in sabotaging immune host cells and how\n            <jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>\n            spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in\n            <jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>\n            physiology and in shaping host-\n            <jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>\n            interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a \u0394\n            <jats:italic>bpdA<\/jats:italic>\n            phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the \u0394\n            <jats:italic>bpdA<\/jats:italic>\n            mutant induced a weaker host immune response than did wild-type\n            <jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>\n            or the low-c-di-GMP guanylate cyclase \u0394\n            <jats:italic>cgsB<\/jats:italic>\n            mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, \u0394\n            <jats:italic>bpdA<\/jats:italic>\n            mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing\n            <jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>\n            to successfully navigate stressful and shifting environments to establish intracellular infection.\n          <\/jats:p>","DOI":"10.1128\/iai.00531-16","type":"journal-article","created":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T03:14:22Z","timestamp":1474946062000},"page":"3458-3470","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response"],"prefix":"10.1128","volume":"84","author":[{"given":"Mike","family":"Khan","sequence":"first","affiliation":[{"name":"Cellular and Molecular Pathology Training Program, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome S.","family":"Harms","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin-Madison School of Veterinary Medicine, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda M.","family":"Marim","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte-Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Armon","sequence":"additional","affiliation":[{"name":"Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherisse L.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of 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