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J Clin Invest. 2018 Oct 1;128(10):4639-4653. doi: 10.1172/JCI99490. Epub 2018 Sep 10.

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

Author information

1
Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health and.
2
Department of Computational and System Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
3
Institute of Physics, Nicolaus Copernicus University, Torun, Poland.
4
Department of Cell Biology.
5
Department of Critical Care Medicine.
6
Department of Microbiology and Molecular Genetics, and.
7
Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
8
Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, USA.
9
Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California, USA.
10
Department of Medicine and.
11
Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
12
Medical Specialty Service Line, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.
13
Department of Chemistry and.
14
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
15
Laboratory of Navigational Redox Lipidomics, Institute of Regenerative Medicine, IM Sechenov Moscow State Medical University, Moscow, Russia.

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.

KEYWORDS:

Bacterial infections; Cell Biology; Infectious disease

PMID:
30198910
PMCID:
PMC6159971
[Available on 2019-01-01]
DOI:
10.1172/JCI99490
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