Transferrin-mediated iron sequestration as a novel therapy for bacterial and fungal infections.
Transferrin-mediated iron sequestration as a novel therapy for bacterial and fungal infections.
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DOI：
10.1016/j.mib.2015.07.005
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发表时间：
2015-10
影响因子：
5.4
通讯作者：
Spellberg B
中科院分区：
文献类型：
--
作者：
Bruhn KW;Spellberg B
病原微生物必须从宿主那里获得必要的营养，包括铁，才能繁殖并引起感染。铁封存是一种古老的宿主抗菌策略。因此，加强铁的封存是一种很有前途的新的抗感染策略。不幸的是，小分子铁络合剂已被证明很难作为抗感染治疗开发，部分原因是不可接受的毒性。哺乳动物体内铁的固存主要是由铁结合蛋白的转铁蛋白家族介导的。在这篇综述中，我们探讨了应用超生理水平的外源性转铁蛋白作为感染的铁隔离疗法的可能性，这可以克服与小分子螯合相关的一些问题。最近的研究表明，转铁蛋白传递可能是一种有希望的方法，既可以增强自然耐药性，也可以增强传统的抗生素治疗。
Pathogenic microbes must acquire essential nutrients, including iron, from the host in order to proliferate and cause infections. Iron sequestration is an ancient host antimicrobial strategy. Thus, enhancing iron sequestration is a promising, novel anti-infective strategy. Unfortunately, small molecule iron chelators have proven difficult to develop as anti-infective treatments, in part due to unacceptable toxicities. Iron sequestration in mammals is predominantly mediated by the transferrin family of iron-binding proteins. In this review, we explore the possibility of administering supraphysiological levels of exogenous transferrin as an iron sequestering therapy for infections, which could overcome some of the problems associated with small molecule chelation. Recent studies suggest that transferrin delivery may represent a promising approach to augment both natural resistance and traditional antibiotic therapy.