Iron is an essential nutrient for bacterial growth and the cause of a fierce battle between the pathogen and host during infection. Bacteria have developed several strategies to access iron from the host, the most common being the production of siderophores, small iron-chelating molecules secreted into the bacterial environment. The opportunist pathogen Pseudomonas aeruginosa produces two siderophores, pyoverdine and pyochelin, and is also able to use a wide panoply of xenosiderophores, siderophores produced by other microorganisms. Here, we demonstrate that catecholamine neurotransmitters (dopamine, l-DOPA, epinephrine and norepinephrine) are able to chelate iron and efficiently bring iron into P. aeruginosa cells via TonB-dependent transporters (TBDTs). Bacterial growth assays under strong iron-restricted conditions and with numerous mutants showed that the TBDTs involved are PiuA and PirA. PiuA exhibited more pronounced specificity for dopamine uptake than for norepinephrine, epinephrine and l-DOPA, whereas PirA specificity appeared to be higher for l-DOPA and norepinephrine. Proteomic and qRT-PCR approaches showed pirA transcription and expression to be induced in the presence of all four catecholamines. Finally, the oxidative properties of catecholamines enable them to reduce iron, and we observed ferrous iron uptake via the FeoABC system in the presence of l-DOPA.

中文翻译：

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铜绿假单胞菌利用儿茶酚胺神经递质作为铁载体获取铁的机会性使用

铁是细菌生长的必需营养素，也是感染过程中病原体与宿主之间激烈战斗的原因。细菌已经开发出几种从宿主获取铁的策略，最常见的是产生铁载体，即分泌到细菌环境中的小铁螯合分子。机会主义病原体铜绿假单胞菌产生两种铁载体，pyoverdine 和 pyochelin，并且还能够使用由其他微生物产生的大量异铁载体，即铁载体。在这里，我们证明了儿茶酚胺神经递质（多巴胺、左旋多巴、肾上腺素和去甲肾上腺素）能够螯合铁并有效地将铁带入P。绿脓杆菌细胞通过 TonB 依赖性转运蛋白 (TBDT)。在强铁限制条件下和许多突变体的细菌生长试验表明，所涉及的 TBDT 是 PiuA 和 PirA。PiuA 对多巴胺摄取表现出比对去甲肾上腺素、肾上腺素和左旋多巴更明显的特异性，而PirA对左旋多巴和去甲肾上腺素的特异性似乎更高。蛋白质组学和 qRT-PCR 方法显示pirA转录和表达在所有四种儿茶酚胺存在下被诱导。最后，儿茶酚胺的氧化特性使它们能够还原铁，我们观察到在l- DOPA 存在下通过 FeoABC 系统吸收亚铁。