Fluconazole-Decorated Gold Nanoparticles as a Novel Therapeutic Strategy Against Carbapenem-Resistant Klebsiella pneumoniae.

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.