A Common Platform for Antibiotic Dereplication and Adjuvant Discovery
A Common Platform for Antibiotic Dereplication and Adjuvant Discovery
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DOI：
10.1016/j.chembiol.2016.11.011
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发表时间：
2017-01-19
影响因子：
8.6
通讯作者：
Wright, Gerard D.
中科院分区：
文献类型：
--
作者：
Cox, Georgina;Sieron, Arthur;Wright, Gerard D.
解决抗生素耐药性危机需要发现新的抗微生物药物并保护现有药物。抗生素耐药性抑制剂，抗生素佐剂的发现，是后者的一个证明的例子。鉴定新抗生素的一个主要困难是已知化合物的频繁重新发现，需要费力的“去复制”来鉴定新的化学实体。我们已经开发了一个抗生素耐药性平台（阿普），可用于鉴定抗生素佐剂和抗生素去复制。阿普是在相同的遗传背景中的机械上不同的个体抗性元件的基于细胞的阵列。在去复制模式中，我们展示了常见抗生素的快速鉴定和鉴别。在佐剂发现模式中，我们表明阿普可以在筛选中用于识别耐药抑制剂。因此，阿普是一个强大的工具，在应对抵抗危机方面具有广泛的应用。
Solving the antibiotic resistance crisis requires the discovery of new antimicrobial drugs and the preservation of existing ones. The discovery of inhibitors of antibiotic resistance, antibiotic adjuvants, is a proven example of the latter. A major difficulty in identifying new antibiotics is the frequent rediscovery of known compounds, necessitating laborious "dereplication'' to identify novel chemical entities. We have developed an antibiotic resistance platform (ARP) that can be used for both the identification of antibiotic adjuvants and for antibiotic dereplication. The ARP is a cell-based array of mechanistically distinct individual resistance elements in an identical genetic background. In dereplication mode, we demonstrate the rapid identification, and thus discrimination, of common antibiotics. In adjuvant discovery mode, we show that the ARP can be harnessed in screens to identify inhibitors of resistance. The ARP is therefore a powerful tool that has broad application in confronting the resistance crisis.