Pathogenic bacteria must secure the uptake of nutritional metals such as iron for their growth, making their import systems attractive targets for the development of new antimicrobial modalities. In the pathogenic bacterium Streptococcus pyogenes, the iron uptake system FtsABCD transports iron encapsulated by siderophores of the hydroxamate class. However, the inability of S. pyogenes to produce these metabolites makes the biological and clinical relevance of this route unresolved. Herein, we demonstrated that the periplasmic binding protein FtsB recognizes not only the hydroxamate siderophore ferrichrome, as previously documented, but also ferrioxamine E (FOE), ferrioxamine B (FOB), and bisucaberin (BIS), each of them with high affinity (nM level). Up to seven aromatic residues in the binding pocket accommodate the variable backbones of the different siderophores through CH-π interactions, explaining ligand promiscuity. Collectively, our observations revealed how S. pyogenes exploits the diverse xenosiderophores produced by other microorganisms as iron sources to secure this precious nutrient.

中文翻译：

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来自化脓性链球菌的异羟肟酸铁载体结合蛋白 FtsB 配体混杂的结构基础


病原菌必须确保吸收营养金属（如铁）以促进其生长，这使得它们的进口系统成为开发新抗菌方式的有吸引力的目标。在致病菌化脓性链球菌中，铁摄取系统 FtsABCD 运输被异羟肟酸盐类铁载体包裹的铁。然而，化脓性链球 菌无法产生这些代谢物使得该途径的生物学和临床相关性尚未解决。在此，我们证明周质结合蛋白 FtsB 不仅识别先前记录的异羟肟酸铁载体铁铬，还识别铁氧胺 E （FOE）、铁氧胺 B （FOB） 和双硫卡百灵 （BIS），它们中的每一种都具有高亲和力 （nM 水平）。结合口袋中多达 7 个芳香族残基通过 CH-π 相互作用容纳不同铁载体的可变骨架，解释了配体混杂。总的来说，我们的观察揭示了化脓性链球菌 如何利用其他微生物产生的各种异铁载体作为铁源来确保这种珍贵的营养物质。