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首页> 外文期刊>IUCrJ >Determination of the molecular basis for coprogen import by Gram-negative bacteria
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Determination of the molecular basis for coprogen import by Gram-negative bacteria

机译：革兰氏阴性菌输入辅生的分子基础的确定

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摘要

In order to survive in mixed microbial communities, some species of fungi secrete coprogens, siderophores that facilitate capture of the scarce nutrient iron. The TonB-dependent transporter FhuE is integrated in the outer membrane of Gram-negative bacteria and has been reported to scavenge these fungally produced coprogens. In this work, an Escherichia coli strain was engineered that is dependent solely on FhuE for its access to siderophore-sequestered iron. Using this tool, it is shown that while FhuE is highly active in the import of coprogens, it has some level of promiscuity, acting as a low-affinity transporter for related siderophores. The crystal structure of FhuE in complex with coprogen was determined, providing a structural basis to explain this selective promiscuity. The structural data, in combination with functional analysis, presented in this work show that FhuE has evolved to specifically engage with planar siderophores. A potential evolutionary driver, and a critical consequence of this selectivity, is that it allows FhuE to exclude antibiotics that mimic nonplanar hydroxamate siderophores: these toxic molecules could otherwise cross the outer membrane barrier through a Trojan horse mechanism.
机译：为了在混合的微生物群落中生存，某些真菌会分泌辅生素，铁载体有助于捕获稀有的营养铁。依赖TonB的转运蛋白FhuE整合在革兰氏阴性细菌的外膜中，据报道它可以清除这些真菌产生的辅助原。在这项工作中，工程改造了一个仅依赖于FhuE的大肠埃希氏菌铁螯合菌株。使用该工具表明，尽管FhuE在辅生子的导入中非常活跃，但它具有一定程度的混杂性，充当相关铁载体的低亲和力转运蛋白。确定了FhuE与辅原配合物的晶体结构，为解释这种选择性混杂提供了结构基础。结合这项工作提出的结构数据和功能分析表明，FhuE已经进化为专门与平面铁载体结合。潜在的进化驱动力和这种选择性的关键结果是，它允许FhuE排除模仿非平面异羟肟酸酯铁载体的抗生素：否则，这些有毒分子可能通过特洛伊木马机制穿越外膜屏障。

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