Serious infection caused by multi-drug-resistant bacteria is a major threat to human health. Bacteria can invade the host tissue and produce various toxins to damage or kill host cells, which may induce life-threatening sepsis. Here, we aimed to explore whether fructose-coated Ångstrom-scale silver particles (F-AgÅPs), which were prepared by our self-developed evaporation-condensation system and optimized coating approach, could kill bacteria and sequester bacterial toxins to attenuate fatal bacterial infections./nMethods: A series of in vitro assays were conducted to test the anti-bacterial efficacy of F-AgÅPs, and to investigate whether F-AgÅPs could protect against multi-drug resistant Staphylococcus aureus (S. aureus)- and Escherichia coli (E. coli)-induced cell death, and suppress their toxins (S. aureus hemolysin and E. coli lipopolysaccharide)-induced cell injury or inflammation. The mouse models of cecal ligation and puncture (CLP)- or E. coli bloodstream infection-induced lethal sepsis were established to assess whether the intravenous administration of F-AgÅPs could decrease bacterial burden, inhibit inflammation, and improve the survival rates of mice. The levels of silver in urine and feces of mice were examined to evaluate the excretion of F-AgÅPs./nResults: F-AgÅPs efficiently killed various bacteria that can cause lethal infections and also competed with host cells to bind with S. aureus α-hemolysin, thus blocking its cytotoxic activity. F-AgÅPs inhibited E. coli lipopolysaccharide-induced endothelial injury and macrophage inflammation, but not by directly binding to lipopolysaccharide. F-AgÅPs potently reduced bacterial burden, reversed dysregulated inflammation, and enhanced survival in mice with CLP- or E. coli bloodstream infection-induced sepsis, either alone or combined with antibiotic therapy. After three times injections within 48 h, 79.18% of F-AgÅPs were excreted via feces at the end of the 14-day observation period./nConclusion: This study suggests the prospect of F-AgÅPs as a promising intravenous agent for treating severe bacterial infections.

中文翻译：

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果糖涂层 Ångstrom 银通过杀死细菌和减轻细菌毒素引起的损伤来预防败血症

多重耐药菌引起的严重感染是对人类健康的重大威胁。细菌可以侵入宿主组织并产生各种毒素来破坏或杀死宿主细胞，这可能导致危及生命的败血症。在这里，我们旨在探索通过我们自主开发的蒸发-冷凝系统和优化的涂层方法制备的果糖涂层埃级银颗粒 (F-AgÅPs) 是否可以杀死细菌并隔离细菌毒素以减轻致命的细菌感染./n方法：进行了一系列体外试验以测试 F-AgÅPs 的抗菌功效，并研究 F-AgÅPs 是否可以防止多重耐药金黄色葡萄球菌( S. aureus ) 和大肠杆菌（E.coli）诱导细胞死亡，并抑制其毒素（金黄色葡萄球菌溶血素和大肠杆菌脂多糖）诱导的细胞损伤或炎症。建立了盲肠结扎和穿刺 (CLP) 或大肠杆菌血流感染引起的致死性败血症的小鼠模型，以评估静脉注射 F-AgÅPs 是否可以减少细菌负荷、抑制炎症和提高小鼠的存活率。检查小鼠尿液和粪便中的银含量以评估 F-AgÅPs 的排泄情况。/n结果： F-AgÅPs 有效杀死各种可导致致命感染的细菌，并与宿主细胞竞争与金黄色葡萄球菌结合α-溶血素，从而阻断其细胞毒活性。F-AgÅPs 抑制大肠杆菌脂多糖诱导的内皮损伤和巨噬细胞炎症，但不是通过直接与脂多糖结合。F-AgÅPs可单独或与抗生素治疗联合使用，有效降低 CLP 或大肠杆菌血流感染引起的败血症小鼠的细菌负担、逆转炎症失调并提高存活率。在 48 小时内注射 3 次后，在 14 天观察期结束时，79.18% 的 F-AgÅPs通过粪便排出。/n结论：本研究表明 F-AgÅPs 作为治疗重症患者的静脉注射药物的前景细菌感染。