CNRS, UMR7242, ESBS, Université de Strasbourg, Bld Sébastien Brant, F-67412 Illkirch, France.
The Hamburg Centre for Ultrafast Imaging, University of Hamburg, Hamburg, Germany.
ACS Chem Biol. 2020 Oct 16;15(10):2741-2751. doi: 10.1021/acschembio.0c00535. Epub 2020 Sep 24.
Iron is a key nutrient for almost all living organisms. Paradoxically, it is poorly soluble and consequently poorly bioavailable. Bacteria have thus developed multiple strategies to access this metal. One of the most common consists of the use of siderophores, small compounds that chelate ferric iron with very high affinity. Many bacteria are able to produce their own siderophores or use those produced by other microorganisms (exosiderophores) in a piracy strategy. produces two siderophores, pyoverdine and pyochelin, and is also able to use a large panel of exosiderophores. We investigated the ability of to use nocardamine (NOCA) and ferrioxamine B (DFOB) as exosiderophores under iron-limited planktonic growth conditions. Proteomic and RT-qPCR approaches showed induction of the transcription and expression of the outer membrane transporter FoxA in the presence of NOCA or DFOB in the bacterial environment. Expression of the proteins of the heme- or pyoverdine- and pyochelin-dependent iron uptake pathways was not affected by the presence of these two tris-hydroxamate siderophores. Fe uptake assays using mutants showed ferri-NOCA to be exclusively transported by FoxA, whereas ferri-DFOB was transported by FoxA and at least one other unidentified transporter. The crystal structure of FoxA complexed with NOCA-Fe revealed very similar siderophore binding sites between NOCA-Fe and DFOB-Fe. We discuss iron uptake by hydroxamate exosiderophores in cells in light of these results.
铁是几乎所有生物体的关键营养物质。矛盾的是，它的溶解度很差，因此生物利用度也很差。细菌因此发展了多种获取这种金属的策略。最常见的策略之一是使用铁载体，即与三价铁具有非常高亲和力的螯合铁的小分子化合物。许多细菌能够产生自己的铁载体，或者在盗用策略中使用其他微生物（外铁载体）产生的铁载体。 产生两种铁载体，即绿脓菌素和焦脱镁叶绿酸，并且还能够使用大量的外铁载体。我们研究了 在浮游生长条件下，在缺铁的情况下，利用诺卡霉素 (NOCA) 和去铁胺 B (DFOB) 作为外铁载体的能力。蛋白质组学和 RT-qPCR 方法表明，在外铁载体的存在下，FoxA 外膜转运蛋白的转录和表达被诱导。血红素或绿脓菌素和焦脱镁叶绿酸依赖的铁摄取途径的蛋白质表达不受这两种三羟甲氨基甲酸盐铁载体的存在影响。使用 突变体进行的铁摄取测定表明，Ferri-NOCA 仅由 FoxA 转运，而 Ferri-DFOB 由 FoxA 和至少一种其他未识别的转运体转运。与 DFOB-Fe 结合的 FoxA 复合物的晶体结构揭示了 NOCA-Fe 和 DFOB-Fe 之间非常相似的铁载体结合位点。我们根据这些结果讨论了 细胞对羟甲氨基甲酸盐外铁载体的铁摄取。
