{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:16:03Z","timestamp":1768508163180,"version":"3.49.0"},"posted":{"date-parts":[[2023,9,28]]},"group-title":"Microbiology","reference-count":46,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,20]]},"abstract":"<jats:title>Abstract<\/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 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. In our earlier study the pyrin inflammasome was dispensable for lung inflammation in mice infected with\n                  <jats:italic>B. orbicola<\/jats:italic>\n                  AU1054, indicating this species activates an alternative pathway of macrophage inflammatory death. Notably,\n                  <jats:italic>B. cenocepacia<\/jats:italic>\n                  J2315 and K56-2 can damage macrophage phagosomes and K56-2 triggers activation of the caspase-11 inflammasome, which detects cytosolic LPS. Here we investigated inflammatory cell death in pyrin-deficient (\n                  <jats:italic>Mefv<\/jats:italic>\n                  <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  ) 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, release of cytokines IL-1\u03b1 and IL-1\u03b2 and plasma membrane rupture. Findings suggest that J2315 and K56-2 are detected by the caspase-11 inflammasome in\n                  <jats:italic>Mefv<\/jats:italic>\n                  <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  macrophages, resulting in IL-1\u03b2 release. In contrast, inflammasome activation is not detected in\n                  <jats:italic>Mefv<\/jats:italic>\n                  <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  macrophages infected with AU1054 or PC184. Instead, AU1054 triggers an alternative macrophage inflammatory death pathway that requires TecA and results in plasma membrane rupture and IL-1\u03b1 release. Amino acid variation between TecA isoforms in\n                  <jats:italic>B. cenocepacia<\/jats:italic>\n                  and\n                  <jats:italic>B. orbicola<\/jats:italic>\n                  may explain how the latter species triggers a non-inflammasome macrophage death pathway.\n                <\/jats:p>","DOI":"10.1101\/2023.09.28.559184","type":"posted-content","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T22:45:12Z","timestamp":1695941112000},"source":"Crossref","is-referenced-by-count":1,"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":"10.64898","author":[{"given":"Nicole A.","family":"Loeven","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianna D.","family":"Reuven","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail P.","family":"McGee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarrisa","family":"Dabi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethany W.","family":"Mwaura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6047-8837","authenticated-orcid":false,"given":"James 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