New or repurposed antibiotics are desperately needed since bacterial resistance has risen to essentially all of our current antibiotics, and few new antibiotics have been developed over the last several decades. A primary cause of drug resistance is the overuse of antibiotics that can result in alteration of microbial permeability, alteration of drug target binding sites, induction of enzymes that destroy antibiotics (i.e., β-lactamases) and even induction of efflux mechanisms. Research efforts are described that are designed to determine if the known critical dependence of iron assimilation by microbes for growth and virulence can be exploited for the development of new approaches to antibiotic therapy. Iron recognition and active transport relies on the biosyntheses and use of microbe-selective iron chelating compounds called siderophores. Several natural siderophore-antibiotic conjugates (sideromycins) have been discovered and studied. The natural sideromycins consist of an iron binding siderophore linked to a warhead that exerts antibiotic activity once assimilated by targeted bacteria. Inspired these natural conjugates, a combination of chemical syntheses, microbiological and biochemical studies have been used to generate semi-synthetic and totally synthetic sideromycin analogs. The results demonstrate that siderophores and analogs can be used for iron transport-mediated drug delivery ("Trojan Horse" antibiotics or sideromycins) and induction of iron limitation/starvation (development of new agents to block iron assimilation). While several examples illustrate that this approach can generate microbe selective antibiotics that are active in vitro, the scope and limitations of this approach, especially related to development of resistance, siderophore based molecular recognition requirements, appropriate linker and drug choices, will be described.

中文翻译：

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合成铁霉素（怀疑和乐观）：选择性地产生广谱或窄谱的革兰氏阴性抗生素。

迫切需要新的或重新使用的抗生素，因为细菌耐药性已基本上升到我们目前所有的抗生素中，并且在过去的几十年中很少开发出新的抗生素。耐药性的主要原因是抗生素的过度使用，会导致微生物通透性的改变，药物靶结合位点的改变，诱导破坏抗生素的酶（即β-内酰胺酶）甚至外排机制的诱导。描述了旨在确定是否可以利用微生物对铁的同化对生长和毒力的关键性依赖性的研究工作，以开发新的抗生素治疗方法。铁的识别和主动转运取决于生物合成和微生物选择性铁螯合化合物（称为铁载体）的使用。已经发现和研究了几种天然的铁载体-抗生素结合物（sideromycins）。天然铁霉素由与弹头连接的铁结合铁载体组成，一旦被目标细菌吸收，弹头就发挥抗生素活性。受到这些天然缀合物的启发，化学合成，微生物学和生化研究的组合已用于生成半合成和完全合成的铁霉素类似物。结果表明铁载体和类似物可用于铁转运介导的药物递送（“特洛伊木马”抗生素或铁霉素）和诱导铁限制/饥饿（开发新的阻断铁同化的药物）。虽然有几个例子说明这种方法可以产生在体外具有活性的微生物选择性抗生素，