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Amphiphilic silver nanoclusters show active nano–bio interaction with compelling antibacterial activity against multidrug-resistant bacteria
NPG Asia Materials ( IF 9.7 ) Pub Date : 2020-09-04 , DOI: 10.1038/s41427-020-00239-y
Yongjiu Chen , Liting Ren , Lingxiao Sun , Xuan Bai , Guoqiang Zhuang , Bin Cao , Guoqing Hu , Nanfeng Zheng , Sijin Liu

Multidrug resistance represents a growing threat to human beings, and alternative antimicrobial regimens to conventional antibiotic paradigms are being extensively searched to fight against multidrug-resistant bacteria (MDRB). Although the antimicrobial potency of silver nanomaterials (AgNMs) has been previously elaborated, their efficacy against MDRB still remains to be strengthened. Here, our data revealed that small-sized silver nanoclusters (AgNCs) are superior to conventional silver nanoparticles (AgNPs) as robust antimicrobials against multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa). The core structure and surface ligands of AgNCs are crucial for the outstanding antibacterial activity of AgNCs. On the one hand, due to the presence of amphiphilic ligands, AgNCs are relatively prone to associate with the cell membrane and partake in endocytosis with targeted bacterial cells. Molecular dynamics simulations also corroborated this finding. On the other hand, the nanocluster structure of AgNCs led to strong peroxidase-like activity associated with massive production of reactive oxygen species (ROS), which contributes to their overall bactericidal potency. These outstanding features of AgNCs result in elevated bacterial killing efficacy by impairing the cell wall/membrane, promoting oxidative stress and attenuating pivotal cellular processes, e.g., ATP synthesis. Notably, AgNCs manifested great efficacy in treating P. aeruginosa-generated pneumonia in mice and increased the survival of infected animals, as well as exhibited excellent biocompatibility. Taken together, the results of this study pinpoint the great promise of AgNCs as new alternative therapeutics against MDR P. aeruginosa.



中文翻译:

两亲性的银纳米团簇显示出活跃的纳米生物相互作用,并具有对耐多药细菌的引人注目的抗菌活性

多药耐药性对人类构成越来越大的威胁,并且正在广泛寻找替代常规抗生素范例的抗菌方案,以对抗多药耐药细菌(MDRB)。尽管先前已经详细阐述了银纳米材料(AgNMs)的抗菌效力,但它们对MDRB的功效仍有待加强。这里,我们的数据显示,小尺寸的银纳米簇(AgNCs)优于常规的银纳米颗粒(的AgNPs)作为对多药耐药(MDR)鲁棒的抗微生物剂铜绿假单胞菌绿脓杆菌)。AgNCs的核心结构和表面配体对于AgNCs出色的抗菌活性至关重要。一方面,由于两亲性配体的存在,AgNCs相对易于与细胞膜结合,并参与目标细菌细胞的内吞作用。分子动力学模拟也证实了这一发现。另一方面,AgNCs的纳米簇结构导致与过氧化物酶类似的活性,与活性氧(ROS)的大量产生有关,这有助于其总体杀菌效力。AgNCs的这些杰出特征通过破坏细胞壁/膜,促进氧化应激并减弱关键的细胞过程(例如ATP合成)而提高了细菌杀灭功效。值得注意的是,AgNCs在治疗铜绿假单胞菌在小鼠中产生肺炎,并增加了被感染动物的存活率,并表现出优异的生物相容性。综上所述,这项研究的结果明确指出了AgNCs有望作为对抗MDR铜绿假单胞菌的新替代疗法。

更新日期:2020-09-05
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