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. 2025 Jun 19:20:7811-7827.
doi: 10.2147/IJN.S515798. eCollection 2025.

Daidzein-Decorated Gold Nanoparticles as a Novel Antimicrobial Strategy Against Carbapenem-Resistant Enterobacteriaceae

Juan Pan  1 , Jia Zhang  2 , Panjie Hu  1 , Zhuocheng Yao  1 , Xiaotuan Zhang  1   3 , Tieli Zhou  1 , Mo Shen  1
Affiliations

Daidzein-Decorated Gold Nanoparticles as a Novel Antimicrobial Strategy Against Carbapenem-Resistant Enterobacteriaceae

Juan Pan et al. Int J Nanomedicine. .

Abstract

Introduction: Bacterial resistance to carbapenems is on the rise, and the failure of common antimicrobials poses a serious challenge in treating infections caused by drug-resistant strains. In this scenario, nanomaterials have received widespread attention in medicine.

Methods: In this study, the activity of daidzein-decorated gold nanoparticles (Daidzein_Au NPs) against carbapenem-resistant Enterobacteriaceae (CRE) strains was validated via in vivo and in vitro experiments, such as the microdilution broth method, growth curves, time-killing assays, and an abdominal infection model in mice. The potential mechanisms involved were examined using fluorescence quantification of N-phenyl-1-naphthylamine, propidium iodide, and reactive oxygen species (ROS) levels and transcriptomic analysis.

Results: Face-centered cubic Daidzein_Au NPs with an average size of 25.78 nm and a negative surface charge were successfully synthesized. The minimum inhibitory concentration (MIC) of Daidzein_Au NPs against the tested CRE strains was 8-16 μg/mL, and they exerted a good antimicrobial effect during the dynamic killing process. In vivo experiments showed that Daidzein_Au NPs can significantly enhance the survival rate (100%) and reduce the colony load of ascites in mice (P < 0.05). Furthermore, Daidzein_Au NPs destroyed the permeability of bacterial cell membranes, increased the production of ROS (P < 0.05), and affected the metabolism of CRE strains to play a role in killing.

Conclusion: Daidzein_Au NPs exhibit excellent antibacterial activity and are expected to become a promising solution to the threats posed by CRE strains.

Keywords: Daidzein; antibacterial mechanism; carbapenem-resistant Enterobacteriaceae; gold nanoparticles.

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Conflict of interest statement

The authors have no conflicts of interest to declare in this work.

Figures

None
Graphical abstract
Figure 1
Figure 1
Characterizations of Daidzein_Au NPs. (A) Ultraviolet absorption spectrum of Daidzein_Au NPs; (B) The XRD pattern of Daidzein_Au NPs; (C) TEM image of Daidzein_Au NPs; (D) FTIR spectra of Daidzein_Au NPs, daidzein, and Au NPs. (E) Characterization of the Zeta potential of Daidzein_Au NPs; (F) Particle size of Daidzein_Au NPs, as analyzed by DLS.
Figure 2
Figure 2
The antimicrobial ability of Daidzein_Au NPs in vitro. Growth curves (A) and time-kill curves (B) of clinical CRE strains after treatment with Daidzein_Au NPs (2 MIC).
Figure 3
Figure 3
Morphological changes of FK9250 strain under SEM after 2 h or 4 h treatment with Daidzein_Au NPs (2 MIC) when compared with the PBS-treatment group. The morphology changes of FK9250 strain multiple bacteria (A) and single bacteria (B) were observed after 2 h or 4 h of treatment with Daidzein_Au NPs (2 MIC).
Figure 4
Figure 4
Changes in the membrane permeability and reactive oxygen species after treatment with Daidzein_Au NPs. The fluorescence intensity of NPN (A) and PI (B) after treatment with different drugs. (C) Fluorescence intensity analysis of intracellular ROS in CRE strains. ***P < 0.001.
Figure 5
Figure 5
The Biocompatibility of Daidzein_Au NPs. (A) The hemolytic effects of Daidzein_Au NPs at different concentrations; (B) Safety assessment of different concentrations of Daidzein_Au NPs in macrophages; (C) Safety assessment of different concentrations of Daidzein_Au NPs in human kidney-derived HK-2 cells; (D) Safety assessment of different concentrations of Daidzein_Au NPs in human HepG2 cells. ***P < 0.001.
Figure 6
Figure 6
The therapeutic effect of Daidzein_Au NPs on mice with abdominal infection. (A) Survival of mice in different treatment groups; (B) Colony loading results of peritoneal lavage fluid in mice of different administration groups. The dotted line represents the minimum detection limit. ***P < 0.001.
Figure 7
Figure 7
Bioinformatics analysis in Daidzein_Au NPs treatment and control FK9250 strains. (A) Visualization of volcano plots of DEGs; (B) GO enrichment analysis of DEGs. Right: up, left: down. (C) KEGG analysis of DEGs between Daidzein_Au NPs treated and control groups. Right: up, left: down.
Figure 8
Figure 8
Heat map of some of the metabolism-related genes.
See this image and copyright information in PMC

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