Targeting iron assimilation to develop new antibacterials.
Targeting iron assimilation to develop new antibacterials.
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DOI：
10.1517/17460441.2012.708335
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发表时间：
2012-09
影响因子：
6.3
通讯作者：
Simeonov A
中科院分区：
文献类型：
--
作者：
Foley TL;Simeonov A
自从首次应用抗生素治疗细菌感染以来，耐药性的发展和传播一直是一个持续的威胁。现代医学需要不断发展的下一代治疗方法，才能领先病原体一步。这篇综述描述了最近的努力，开发药物，中断细菌的铁同化，这是一个过程，是至关重要的细胞内稳态，目前不是在临床上使用的抗生素的目标。我们涵盖了细菌为环境获取铁的机制，并详细介绍了用小分子抑制剂干预这些过程的努力，这些抑制剂针对这些途径中的关键步骤，特别强调了2010-2012年期间发表的最新进展。几十年来，细菌从宿主和环境中吸收铁的途径一直是深入研究的主题。虽然许多研究已经确定了这些途径的抑制剂，但许多研究尚未将体外结果转化为体内概念验证实验。以这种方式扩展初步研究结果以验证铁同化途径用于治疗开发的临床潜力将显着增加该领域的影响。
Since the first application of antibiotics to treat bacterial infections, the development and spread of resistance has been a persistent threat. An ever-evolving pipeline of next-generation therapeutics is required for modern medicine to remain one step ahead of pathogens. This review describes recent efforts to develop drugs that interrupt the assimilation of iron by bacteria, a process that is vital to cellular homeostasis and is not currently targeted by antibiotics used in the clinic. We cover the mechanisms through which bacteria acquire iron for their environment and detail efforts to intervene in these processes with small molecule inhibitors that target key steps in these pathways, with a special emphasis on recent advances published during the 2010–2012 period. For decades, the routes used by bacteria to assimilate iron from host and environmental settings have been the subject of intense study. While numerous investigations have identified inhibitors of these pathways, many have stopped short of translating the in vitro results to in vivo proof of concept experiments. Extension of preliminary findings in this manner to validate the clinical potential of iron assimilation pathways for therapeutic development will significantly increase the impact of the field.
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