Copper Clusters: An Effective Antibacterial for Eradicating Multidrug‐Resistant Bacterial Infection In Vitro and In Vivo
Copper Clusters: An Effective Antibacterial for Eradicating Multidrug‐Resistant Bacterial Infection In Vitro and In Vivo
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DOI：
10.1002/adfm.202008720
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发表时间：
2021-01
影响因子：
19
通讯作者：
Xiangchun Zhang;Zhichao Zhang;Qingming Shu;Chao Xu;Qinqin Zheng;Zhao Guo;Chen Wang;Zhenxia Hao;Xin Liu;Guoqing Wang;Wangjun Yan;Hongping Chen;Chengyin Lu
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作者：
Xiangchun Zhang;Zhichao Zhang;Qingming Shu;Chao Xu;Qinqin Zheng;Zhao Guo;Chen Wang;Zhenxia Hao;Xin Liu;Guoqing Wang;Wangjun Yan;Hongping Chen;Chengyin Lu
由多药耐药(MDR)细菌引起的感染在全球范围内威胁着人类的健康，迫切需要新的有效的抗菌剂。到目前为止，开发具有明确抗菌机制的新型抗菌药物仍然是一个巨大的挑战。在这里，利用人工设计的茶氨酸多肽精确地合成了一种新的替代抗菌铜簇合物(CUCs)分子。所制备的CUCs具有良好的体外广谱抗菌活性，包括革兰氏阳性菌(耐甲氧西林金黄色葡萄球菌、金黄色葡萄球菌和表皮葡萄球菌)和革兰氏阴性菌(大肠杆菌和铜绿假单胞菌)。这种强大的抗菌作用是因为它不仅能够破坏细菌的壁结构，而且可以通过抑制谷胱甘肽还原酶的活性来调节GSH/GSSG的比例，从而导致活性氧的爆发，最终导致细菌死亡。此外，体内研究表明，CUCS可以显著挽救MRSA引起的小鼠皮肤伤口感染和脓毒症，与莫匹罗星软膏和临床一线锚定的抗MRSA药物万古霉素具有相同的治疗效果。此外，与银团簇和铂簇相比，CUCs对正常哺乳动物细胞的细胞毒性极低。随着进一步的开发和优化，CUCs作为一类新型抗菌剂在对抗抗生素耐药病原菌方面具有巨大的潜力。
Infections caused by multidrug‐resistant (MDR) bacteria pose a threat to human health worldwide, making new effective antibacterial agents urgently desired. To date, it is still a great challenge to develop new antibiotics for MDR bacteria with clear antibacterial mechanisms. Herein, a novel alternative antibacterial copper clusters (CuCs) molecule is precisely synthesized utilizing an artificially designed theanine peptide. The prepared CuCs exhibit excellent broad‐spectrum antibacterial activity in vitro, including gram‐positive bacteria (methicillin‐resistant Staphylococcus aureus [MRSA], Staphylococcus aureus, and Staphylococcus epidermidis) and gram‐negative bacteria (Escherichia coli and Pseudomonas aeruginosa). The robust antibacterial effect is due to its ability to not only destroy the bacterial wall structure, but also regulate the ratio of GSH/GSSG by inhibiting the activity of glutathione reductase, thus causing the outbreak of reactive oxygen species and ultimately leading to bacterial death. In addition, in vivo studies demonstrate that CuCs can significantly rescue skin wound infections and sepsis in mice caused by MRSA, and has the same therapeutic efficacy as mupirocin ointment and first‐line clinically anchored anti‐MRSA drug vancomycin. Moreover, CuCs exhibit extremely low cytotoxicity to normal mammalian cells compared to silver and platinum clusters. With further development and optimization, CuCs has great potential as a new class of antibacterial agents to fight antibiotic‐resistant pathogens.