TY - JOUR AU - Dar, Haider H. AU - Tyurina, Yulia Y. AU - Mikulska-Ruminska, Karolina AU - Shrivastava, Indira AU - Ting, Hsiu-Chi AU - Tyurin, Vladimir A. AU - Krieger, James AU - St. Croix, Claudette M. AU - Watkins, Simon AU - Bayir, Erkan AU - Mao, Gaowei AU - Armbruster, Catherine R. AU - Kapralov, Alexandr AU - Wang, Hong AU - Parsek, Matthew R. AU - Anthonymuthu, Tamil S. AU - Ogunsola, Abiola F. AU - Flitter, Becca A. AU - Freedman, Cody J. AU - Gaston, Jordan R. AU - Holman, Theodore R. AU - Pilewski, Joseph M. AU - Greenberger, Joel S. AU - Mallampalli, Rama K. AU - Doi, Yohei AU - Lee, Janet S. AU - Bahar, Ivet AU - Bomberger, Jennifer M. AU - Bayır, Hülya AU - Kagan, Valerian E. T1 - Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium PY - 2019/03/15/ AB - Ferroptosis is a death program executed via selective oxidation of arachidonic acid–phosphatidylethanolamines (AA-PE) by 15-lipoxygenases. In mammalian cells and tissues, ferroptosis has been pathogenically associated with brain, kidney, and liver injury/diseases. We discovered that a prokaryotic bacterium, Pseudomonas aeruginosa, that does not contain AA-PE can express lipoxygenase (pLoxA), oxidize host AA-PE to 15-hydroperoxy-AA-PE (15-HOO-AA-PE), and trigger ferroptosis in human bronchial epithelial cells. Induction of ferroptosis by clinical P. aeruginosa isolates from patients with persistent lower respiratory tract infections was dependent on the level and enzymatic activity of pLoxA. Redox phospholipidomics revealed elevated levels of oxidized AA-PE in airway tissues from patients with cystic fibrosis (CF) but not with emphysema or CF without P. aeruginosa. We believe that the evolutionarily conserved mechanism of pLoxA-driven ferroptosis may represent a potential therapeutic target against P. aeruginosa–associated diseases such as CF and persistent lower respiratory tract infections. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI99490 VL - 128 IS - 10 UR - https://doi.org/10.1172/JCI99490 SP - 4639 EP - 4653 PB - The American Society for Clinical Investigation ER -