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. Methods: 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. Results: 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. Conclusion: This study suggests the prospect of F-AgÅPs as a promising intravenous agent for treating severe bacterial infections.

Background: The iron acquisition ability of hypervirulent Klebsiella pneumoniae (hvKP) is an important part of its super virulence mechanism, increasing studies have proved that outer membrane vesicles (OMVs) are involved in the iron acquisition process of bacteria. Thus, we compared the difference in RNA expression in OMVs of hvKP in iron-rich and iron-deficient medium, and explore the possible mechanism of RNA in OMVs involved in hvKP iron acquisition. Results: The results of high-throughput sequencing showed that in iron-deficient medium, there were 239 up-regulated and 89 down-regulated mRNAs in OMVs of hvKP, of which 20 mRNAs related to iron transport was up-regulated, mainly including siderophore synthesis and receptor genes, ATP binding cassette transporter family and iron sulfur cluster. Only two of the differential ncRNAs that regulate these mRNAs are up-regulated, which are lncRNAs.Conclusion: We demonstrated that mRNA and lncRNA in OMVs were directly or indirectly involved in the iron acquisition mechanism of hvKP under iron deficiency environment, which enhanced the adaptive survival ability of hvKP. It provided a basis for further exploring the iron acquisition mechanism of OMVs involved in hvKP.

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