生物膜
耐甲氧西林金黄色葡萄球菌
抗性(生态学)
生物
葡萄球菌感染
万古霉素
流出
利奈唑啉
青霉素结合蛋白
细菌
医学
作者
Haibo Wang,Minji Wang,Xiaohan Xu,Peng Gao,Zeling Xu,Qi Zhang,Hongyan Li,Aixin Yan,Richard Y.T. Kao,Hongzhe Sun
标识
DOI:10.1038/s41467-021-23659-y
摘要
The rapid emergence of drug resistant Staphylococcus aureus (S. aureus) poses a serious threat to public health globally. Silver (Ag)-based antimicrobials are promising to combat antibiotic resistant S. aureus, yet their molecular targets are largely elusive. Herein, we separate and identify 38 authentic Ag+-binding proteins in S. aureus at the whole-cell scale. We then capture the molecular snapshot on the dynamic action of Ag+ against S. aureus and further validate that Ag+ could inhibit a key target 6-phosphogluconate dehydrogenase through binding to catalytic His185 by X-ray crystallography. Significantly, the multi-target mode of action of Ag+ (and nanosilver) endows its sustainable antimicrobial efficacy, leading to enhanced efficacy of conventional antibiotics and resensitization of MRSA to antibiotics. Our study resolves the long-standing question of the molecular targets of silver in S. aureus and offers insights into the sustainable bacterial susceptibility of silver, providing a potential approach for combating antimicrobial resistance.
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