Infection and drug resistance · 2026
Fluconazole-Decorated Gold Nanoparticles as a Novel Therapeutic Strategy Against Carbapenem-Resistant Klebsiella pneumoniae.
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Yang Yuhan, Pan Juan, Zhong Zeyong, Gong Yanchun, Yao Zhuocheng, Zhou Tieli, Cao Jianming, Xu Chunquan
Аннотация
PURPOSE: The alarming rise of carbapenem-resistant Klebsiella pneumoniae (CRKP) has escalated into a formidable global health threat, because of its steadily increasing resistance rates to therapeutically important antimicrobial treatments. To address this challenge, we synthesized fluconazole-decorated gold nanoparticles (FCZ_Au NPs) and evaluated the antibacterial efficacy.
METHODS: FCZ_Au NPs were synthesized using a one-pot method. Its antimicrobial activity, anti-biofilm activity and antimicrobial mechanisms through antimicrobial susceptibility testing, growth curve analysis, murine model of acute intraperitoneal infection, crystal violet staining, reactive oxygen species (ROS) detection, membrane permeability assay.
RESULTS: As determined by our assays, the minimum inhibitory concentration of FCZ_Au NPs against CRKP was found to be between 4 and 16 μg/mL, indicating strong inhibitory effects on bacterial growth. Furthermore, at the experimental concentrations, FCZ_Au NPs exhibited excellent safety profiles toward red blood cells and mouse RAW264.7 cells. In an acute intra-abdominal infection paradigm, a notable rise in the mice's survival rate and a commensurate decrease in the bacterial burden in peritoneal lavage fluid revealed the in vivo efficiency of FCZ_Au NPs. Investigations into the antibacterial mechanisms revealed that FCZ_Au NPs act by disrupting bacterial cell membranes and enhancing reactive oxygen species production. The crystal violet assay revealed the great potential of FCZ_Au NPs in inhibiting biofilm formation and eradicating mature biofilms.
CONCLUSION: In this study, we utilized the clinically antifungal drug FCZ to modify gold nanoparticles, synthesizing FCZ_Au NPs. Beyond their significant antibacterial activity against CRKP, these nanoparticles also demonstrated a strong ability to combat biofilms. Thus, this study provides a novel strategy for combating CRKP.
METHODS: FCZ_Au NPs were synthesized using a one-pot method. Its antimicrobial activity, anti-biofilm activity and antimicrobial mechanisms through antimicrobial susceptibility testing, growth curve analysis, murine model of acute intraperitoneal infection, crystal violet staining, reactive oxygen species (ROS) detection, membrane permeability assay.
RESULTS: As determined by our assays, the minimum inhibitory concentration of FCZ_Au NPs against CRKP was found to be between 4 and 16 μg/mL, indicating strong inhibitory effects on bacterial growth. Furthermore, at the experimental concentrations, FCZ_Au NPs exhibited excellent safety profiles toward red blood cells and mouse RAW264.7 cells. In an acute intra-abdominal infection paradigm, a notable rise in the mice's survival rate and a commensurate decrease in the bacterial burden in peritoneal lavage fluid revealed the in vivo efficiency of FCZ_Au NPs. Investigations into the antibacterial mechanisms revealed that FCZ_Au NPs act by disrupting bacterial cell membranes and enhancing reactive oxygen species production. The crystal violet assay revealed the great potential of FCZ_Au NPs in inhibiting biofilm formation and eradicating mature biofilms.
CONCLUSION: In this study, we utilized the clinically antifungal drug FCZ to modify gold nanoparticles, synthesizing FCZ_Au NPs. Beyond their significant antibacterial activity against CRKP, these nanoparticles also demonstrated a strong ability to combat biofilms. Thus, this study provides a novel strategy for combating CRKP.