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. Gaston & 10 others Theodore 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

10 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

Fingerprint

Phosphatidylethanolamines
Theft
Pseudomonas aeruginosa
Arachidonic Acid
Epithelium
Cystic Fibrosis
Respiratory Tract Infections
Arachidonate 15-Lipoxygenase
Lipoxygenase
Emphysema
Oxidation-Reduction
Liver Diseases
Epithelial Cells
Bacteria
Kidney
Wounds and Injuries
Brain

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Dar, H. H., Tyurina, Y. Y., Mikulska-Ruminska, K., Shrivastava, I., Ting, H. C., Tyurin, V. A., ... 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
Dar, Haider H. ; Tyurina, Yulia Y. ; Mikulska-Ruminska, Karolina ; Shrivastava, Indira ; Ting, Hsiu Chi ; Tyurin, Vladimir A. ; Krieger, James ; Croix, Claudette M.St ; Watkins, Simon ; Bayir, Erkan ; Mao, Gaowei ; Armbruster, Catherine R. ; Kapralov, Alexandr ; Wang, Hong ; Parsek, Matthew R. ; Anthonymuthu, Tamil S. ; Ogunsola, Abiola F. ; Flitter, Becca A. ; Freedman, Cody J. ; Gaston, Jordan R. ; Holman, Theodore R. ; Pilewski, Joseph M. ; Greenberger, Joel S. ; Mallampalli, Rama K. ; Doi, Yohei ; Lee, Janet S. ; Bahar, Ivet ; Bomberger, Jennifer M. ; Bayır, Hülya ; Kagan, Valerian E. / Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium. In: Journal of Clinical Investigation. 2018 ; Vol. 128, No. 10. pp. 4639-4653.
@article{ab5c855cac504f8fbfb360f67b63b835,
title = "Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium",
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.",
author = "Dar, {Haider H.} and Tyurina, {Yulia Y.} and Karolina Mikulska-Ruminska and Indira Shrivastava and Ting, {Hsiu Chi} and Tyurin, {Vladimir A.} and James Krieger and Croix, {Claudette M.St} and Simon Watkins and Erkan Bayir and Gaowei Mao and Armbruster, {Catherine R.} and Alexandr Kapralov and Hong Wang and Parsek, {Matthew R.} and Anthonymuthu, {Tamil S.} and Ogunsola, {Abiola F.} and Flitter, {Becca A.} and Freedman, {Cody J.} and Gaston, {Jordan R.} and Holman, {Theodore R.} and Pilewski, {Joseph M.} and Greenberger, {Joel S.} and Mallampalli, {Rama K.} and Yohei Doi and Lee, {Janet S.} and Ivet Bahar and Bomberger, {Jennifer M.} and H{\"u}lya Bayır and Kagan, {Valerian E.}",
year = "2018",
month = "10",
day = "1",
doi = "10.1172/JCI99490",
language = "English",
volume = "128",
pages = "4639--4653",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "10",

}

Dar, HH, Tyurina, YY, Mikulska-Ruminska, K, Shrivastava, I, Ting, HC, Tyurin, VA, Krieger, J, Croix, CMS, Watkins, S, Bayir, E, Mao, G, Armbruster, CR, Kapralov, A, Wang, H, Parsek, MR, Anthonymuthu, TS, Ogunsola, AF, Flitter, BA, Freedman, CJ, Gaston, JR, Holman, TR, Pilewski, JM, Greenberger, JS, Mallampalli, RK, Doi, Y, Lee, JS, Bahar, I, Bomberger, JM, Bayır, H & Kagan, VE 2018, 'Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium', Journal of Clinical Investigation, vol. 128, no. 10, pp. 4639-4653. https://doi.org/10.1172/JCI99490

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

In: Journal of Clinical Investigation, Vol. 128, No. 10, 01.10.2018, p. 4639-4653.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium

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 - Croix, Claudette M.St

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.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85054461432&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054461432&partnerID=8YFLogxK

U2 - 10.1172/JCI99490

DO - 10.1172/JCI99490

M3 - Article

VL - 128

SP - 4639

EP - 4653

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 10

ER -