Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium

Haider H. Dar, Yulia Y. Tyurina, Karolina Mikulska-Ruminska, Indira Shrivastava, Hsiu Chi Ting, Vladimir A. Tyurin, James Krieger, Claudette M.St Croix, Simon Watkins, Erkan Bayir, Gaowei Mao, Catherine R. Armbruster, Alexandr Kapralov, Hong Wang, Matthew R. Parsek, Tamil S. Anthonymuthu, Abiola F. Ogunsola, Becca A. Flitter, Cody J. Freedman, Jordan R. GastonTheodore R. Holman, Joseph M. Pilewski, Joel S. Greenberger, Rama K. Mallampalli, Yohei Doi, Janet S. Lee, Ivet Bahar, Jennifer M. Bomberger, Hülya Bayır, Valerian E. Kagan

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4639-4653
Number of pages15
JournalJournal of Clinical Investigation
Volume128
Issue number10
DOIs
Publication statusPublished - 01-10-2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Dar, H. H., Tyurina, Y. Y., Mikulska-Ruminska, K., Shrivastava, I., Ting, H. C., Tyurin, V. A., Krieger, J., Croix, C. M. S., Watkins, S., Bayir, E., Mao, G., Armbruster, C. R., Kapralov, A., Wang, H., Parsek, M. R., Anthonymuthu, T. S., Ogunsola, A. F., Flitter, B. A., Freedman, C. J., ... Kagan, V. E. (2018). Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium. Journal of Clinical Investigation, 128(10), 4639-4653. https://doi.org/10.1172/JCI99490