Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium
Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium
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DOI：
10.1172/jci99490
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发表时间：
2018-10-01
影响因子：
15.9
通讯作者：
Kagan, Valerian E.
中科院分区：
文献类型：
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作者：
Dar, Haider H.;Tyurina, Yulia Y.;Kagan, Valerian E.
铁下垂是一种通过15脂氧合酶选择性氧化花生四烯酸-磷脂酰乙醇胺（AA-PE）而导致的死亡程序。在哺乳动物细胞和组织中，铁下垂与脑、肾和肝损伤/疾病有致病关系。我们发现一种不含AA-PE的原核细菌铜绿假单胞菌（Pseudomonas aeruginosa）可以表达脂氧合酶（pLoxA），将宿主AA-PE氧化为15- hydroperoxide AA-PE (15- ho -AA-PE)，并引发人支气管上皮细胞铁下垂。持续性下呼吸道感染患者的临床铜绿假单胞菌分离株诱导铁下垂依赖于plxa的水平和酶活性。氧化还原磷脂组学显示囊性纤维化（CF）患者气道组织中氧化AA-PE水平升高，而肺气肿或不含铜绿假单胞菌的CF患者气道组织中氧化AA-PE水平升高。我们认为，plxa驱动的铁下垂的进化保守机制可能代表了铜绿假单胞菌相关疾病（如CF和持续性下呼吸道感染）的潜在治疗靶点。
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.