Carbapenem-resistant Enterobacteriaceae (CRE) pose a serious global health threat due to the ineffectiveness of conventional antibiotics, highlighting the need for new therapeutic strategies. This study explores the potential of nitazoxanide (NTZ), a clinically approved broad-spectrum antiparasitic drug, functionalized onto gold nanoparticles (AuNPs) as an antibacterial approach against CRE. NTZAuNPs were synthesized using a one-pot method, and their antibacterial efficacy was assessed through antimicrobial susceptibility testing, bacterial growth analysis, and electron microscopy. Biosafety was evaluated through hemolysis assays and in vivo murine models. The NTZAuNPs showed significant bactericidal activity against CRE, with MICs ranging from 4 to 8 μg/mL, and exhibited favorable biocompatibility. Mechanistic investigations revealed that NTZAuNPs disrupt bacterial membranes, enhance outer membrane permeability, and infiltrate the intracellular environment. Additionally, NTZAuNPs increase reactive oxygen species (ROS) levels and impair bacterial ATP synthesis, suggesting a dual mechanism involving membrane disruption and oxidative stress. In a mouse model of abdominal infection, NTZAuNPs reduced bacterial burden and improved survival rates. These results validate the potential of NTZAuNPs as an effective, low-toxicity treatment for CRE infections, offering a promising alternative to traditional antibiotics.
Yao et al. (Sun,) studied this question.