{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:57Z","timestamp":1792787637033,"version":"4.5.0"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["AI156924,HL114453,AI156923,"],"award-info":[{"award-number":["AI156924,HL114453,AI156923,"]}]},{"name":"NIH","award":["AI145406."],"award-info":[{"award-number":["AI145406."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,22]]},"abstract":"<jats:p>\n                    Total body irradiation (TBI) targets sensitive bone marrow hematopoietic cells and gut epithelial cells, causing their death and inducing a state of immunodeficiency combined with intestinal dysbiosis and nonproductive immune responses. We found enhanced\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    (PAO1) colonization of the gut leading to host cell death and strikingly decreased survival of irradiated mice. The PAO1-driven pathogenic mechanism includes theft-ferroptosis realized via (a) curbing of the host antiferroptotic system, GSH\/GPx4, and (b) employing bacterial 15-lipoxygenase to generate proferroptotic signal \u2014 15-hydroperoxy-arachidonoyl-PE (15-HpETE-PE) \u2014 in the intestines of irradiated and PAO1-infected mice. Global redox phospholipidomics of the ileum revealed that lysophospholipids and oxidized phospholipids, particularly oxidized phosphatidylethanolamine (PEox), represented the major factors that contributed to the pathogenic changes induced by total body irradiation and infection by PAO1. A lipoxygenase inhibitor, baicalein, significantly attenuated animal lethality, PAO1 colonization, intestinal epithelial cell death, and generation of ferroptotic PEox signals. Opportunistic PAO1 mechanisms included stimulation of the antiinflammatory lipoxin A\n                    <jats:sub>4<\/jats:sub>\n                    , production and suppression of the proinflammatory hepoxilin A\n                    <jats:sub>3<\/jats:sub>\n                    , and leukotriene B\n                    <jats:sub>4<\/jats:sub>\n                    . Unearthing complex PAO1 pathogenic\/virulence mechanisms, including effects on the host anti\/proinflammatory responses, lipid metabolism, and ferroptotic cell death, points toward potentially new therapeutic and radiomitigative targets.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.156013","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T12:02:53Z","timestamp":1642507373000},"source":"Crossref","is-referenced-by-count":46,"title":["P. aeruginosa augments irradiation injury via 15-lipoxygenase\u2013catalyzed generation of 15-HpETE-PE and induction of theft-ferroptosis"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9586-7288","authenticated-orcid":true,"given":"Haider H.","family":"Dar","sequence":"first","affiliation":[{"name":"Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6214-6887","authenticated-orcid":true,"given":"Michael W.","family":"Epperly","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3474-1697","authenticated-orcid":true,"given":"Vladimir A.","family":"Tyurin","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A.","family":"Amoscato","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3460-5003","authenticated-orcid":true,"given":"Tamil S.","family":"Anthonymuthu","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8682-928X","authenticated-orcid":true,"given":"Austin B.","family":"Souryavong","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania, 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