Silver potentiates aminoglycoside toxicity by enhancing their uptake
Silver potentiates aminoglycoside toxicity by enhancing their uptake
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DOI：
10.1111/mmi.13687
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发表时间：
2017-07-01
影响因子：
3.6
通讯作者：
Ezraty, Benjamin
中科院分区：
文献类型：
--
作者：
Herisse, Marion;Duverger, Yohann;Ezraty, Benjamin
预计新抗生素的短缺促使人们研究可以作为辅助剂并提高现有抗生素疗效的化学物质。在这项研究中，我们测试了金属与氨基糖苷结合对大肠杆菌存活的影响。氨基糖苷与银的协同组合效果最佳。通过遗传和氨基糖苷摄取测定，我们发现银增强了氨基糖苷的作用，绕过了pmf依赖的步骤，但依赖于蛋白质翻译。我们发现氧化应激或Fe-S簇不稳定不是银增强作用的强制性因素。最后，我们发现银允许氨基糖苷杀死大肠杆菌庆大霉素抗性突变体以及高度顽固的厌氧病原体艰难梭菌。总的来说，这项研究描述了银对氨基糖苷毒性增强作用的分子基础，并表明金属的使用可能为对抗细菌对抗生素的耐药性提供解决方案。
The predicted shortage in new antibiotics has prompted research for chemicals that could act as adjuvant and enhance efficacy of available antibiotics. In this study, we tested the effects of combining metals with aminoglycosides on Escherichia coli survival. The best synergizing combination resulted from mixing aminoglycosides with silver. Using genetic and aminoglycoside uptake assays, we showed that silver potentiates aminoglycoside action in by-passing the PMF-dependent step, but depended upon protein translation. We showed that oxidative stress or Fe-S cluster destabilization were not mandatory factors for silver potentiating action. Last, we showed that silver allows aminoglycosides to kill an E. coli gentamicin resistant mutant as well as the highly recalcitrant anaerobic pathogen Clostridium difficile. Overall this study delineates the molecular basis of silver's potentiating action on aminoglycoside toxicity and shows that use of metals might offer solutions for battling against increased bacterial resistance to antibiotics.