{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:56:13Z","timestamp":1780433773093,"version":"3.54.1"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["BLISKA22G0"],"award-info":[{"award-number":["BLISKA22G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["STANTO19R0"],"award-info":[{"award-number":["STANTO19R0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2024,12,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The\n              <jats:italic>Burkholderia cepacia<\/jats:italic>\n              complex contains opportunistic pathogens that cause chronic infections and inflammation in the lungs of people with cystic fibrosis. Two closely related species within this complex are\n              <jats:italic>Burkholderia cenocepacia<\/jats:italic>\n              and the recently classified\n              <jats:italic>Burkholderia orbicola. B. cenocepacia<\/jats:italic>\n              and\n              <jats:italic>B. orbicola<\/jats:italic>\n              encode a type VI secretion system and the effector TecA, which is detected by the pyrin\/caspase-1 inflammasome, and triggers macrophage inflammatory death. We previously showed that the pyrin inflammasome was dispensable for lung inflammation in mice infected with\n              <jats:italic>B. orbicola<\/jats:italic>\n              AU1054\n              <jats:italic>,<\/jats:italic>\n              indicating this species activates an alternative pathway of macrophage inflammatory death. Notably,\n              <jats:italic>B. cenocepacia<\/jats:italic>\n              strains J2315 and K56-2 can damage macrophage phagosomes, and K56-2 triggers activation of the caspase-11 inflammasome, which detects cytosolic lipopolysaccharide. Here, we investigated inflammatory cell death in pyrin- (\n              <jats:italic>Mefv<\/jats:italic>\n              <jats:sup>-\/-<\/jats:sup>\n              ) or caspase-1\/caspase-11- (\n              <jats:italic>\n                Casp1\/11\n                <jats:sup>-\/-<\/jats:sup>\n              <\/jats:italic>\n              ) deficient mouse macrophages infected with\n              <jats:italic>B. cenocepacia<\/jats:italic>\n              J2315 or K56-2 or\n              <jats:italic>B. orbicola<\/jats:italic>\n              AU1054 or PC184. Macrophage inflammatory death was measured by cleavage of gasdermin D protein, the release of cytokines IL-1\u03b1 and IL-1\u03b2, and plasma membrane rupture. We found that J2315 and K56-2 are detected by the caspase-11 inflammasome in\n              <jats:italic>Mefv<\/jats:italic>\n              <jats:sup>-\/-<\/jats:sup>\n              macrophages, resulting in IL-1\u03b2 release. By contrast, inflammasome activation was not detected in\n              <jats:italic>Mefv<\/jats:italic>\n              <jats:sup>-\/-<\/jats:sup>\n              macrophages infected with AU1054 or PC184. Instead, AU1054 triggered an alternative macrophage inflammatory death pathway that required TecA and resulted in plasma membrane rupture and IL-1\u03b1 release. Structural modeling of TecA orthologs in\n              <jats:italic>B. cenocepacia<\/jats:italic>\n              and\n              <jats:italic>B. orbicola<\/jats:italic>\n              suggested that amino acid changes in the latter may underlie its ability to trigger a non-inflammasome macrophage death pathway.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/iai.00316-24","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T13:00:54Z","timestamp":1730379654000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["A type VI secretion system in\n            <i>Burkholderia<\/i>\n            species\n            <i>cenocepacia<\/i>\n            and\n            <i>orbicola<\/i>\n            triggers distinct macrophage death pathways independent of the pyrin inflammasome"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0464-886X","authenticated-orcid":false,"given":"Nicole A.","family":"Loeven","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College","place":["Hanover, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9711-5174","authenticated-orcid":false,"given":"Clarrisa","family":"Dabi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College","place":["Hanover, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"Pennington","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College","place":["Hanover, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna 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