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Silver nanoflowers coupled with low dose antibiotics enable the highly effective eradication of drug-resistant bacteria.

Due to the global overuse of antibiotics, the issue of multidrug-resistant bacteria (MDR) continuously calls for effective strategies to tackle the antibiotic resistance crisis. Here, we develop a silver nanomaterial with a petal-like structure (namely Ag Nano Flowers, AgNFs). AgNFs are synthesized in an eco-friendly way with bovine serum albumin as an assisting template and stabilizing agent under mild conditions. These AgNFs have desired physical properties, including good dispersion, high stability, and large surface area with an average size in the range of 700-800 nm. We demonstrate AgNFs as a highly effective drug carrier and an adjuvant to restore the susceptibility of drug-resistant E. coli towards standard antibiotics such as norfloxacin and streptomycin. The doses of AgNFs and norfloxacin are reduced by 80% and 90%, respectively, in the combined treatment compared to those used individually. The dose reductions of AgNFs and streptomycin are 80% and 50% in the combined treatment of streptomycin and AgNFs. Through further analysis of the metabolomics and activities of bacteria, we speculate that the synergistic antibacterial efficacy between AgNFs and antibiotics could be explained by the enhanced respiration of bacteria and the up-regulation of the tricarboxylic acid cycle, which in turn increase the release of reactive oxygen species and promote the uptake of antibiotics, thereby eventually eradicating the drug-resistant bacteria.