Gold Nanoparticles Functionalized With 5-Amino-2-Mercaptobenzimidazole: A Promising Antimicrobial Strategy Against Carbapenem-Resistant Gram-Negative Bacteria.

Abstract

Introduction: Carbapenem-resistant gram-negative bacteria (CR-GNB) pose a significant threat to public health and require immediate attention. The development of novel antibacterial agents against CR-GNB has become an urgent priority, and nanomaterials offer promising solutions due to their unique properties. This study introduces 5-amino-2-mercaptobenzimidazole (5-A-2MBI) functionalized gold nanoparticles (5-A-2MBI_Au NPs) and evaluates their antibacterial activity against CR-GNB.

Methods: The 5-A-2MBI_Au NPs was synthesized using a one-pot method. Its biocompatibility, bactericidal properties, and mechanisms of action were systematically characterized through in vivo and in vitro toxicity tests, antimicrobial susceptibility testing, live/dead staining, membrane permeability and reactive oxygen species (ROS) generation assays, as well as transcriptomic analysis.

Results: The results of this study demonstrate that 5-A-2MBI_Au NPs exhibit excellent antibacterial efficacy against carbapenem-resistant gram-negative bacteria with various resistance mechanisms, with a minimum inhibitory concentration (MIC) of 2 μg/mL. In vivo experiments further confirmed that 5-A-2MBI_Au NPs not only possess effective bactericidal activity but also exhibit satisfactory biocompatibility. Mechanistic studies revealed that 5-A-2MBI_Au NPs enhance bacterial membrane permeability, increase the generation of reactive oxygen species, and disrupt intracellular oxidative stress and succinate synthesis, thereby conferring potent antibacterial activity. This study results demonstrate that 5-A-2MBI_Au NPs exhibit notable antibacterial efficacy against CR-GNB, with a minimum inhibitory concentration of 2 μg/mL. The antibacterial mechanism involves enhanced membrane permeability, increased reactive oxygen species production, and interference with intracellular oxidative stress and succinate synthesis. These mechanisms collectively contribute to the potent antibacterial activity of 5-A-2MBI_Au NPs against CR-GNB.

Discussion: 5-A-2MBI_Au NPs are a novel and highly effective antibacterial agent prepared through a simple process using benzimidazole and HAuCl₄•3H₂O. They efficiently eradicate the most challenging multidrug-resistant GNB both in vitro and in vivo while demonstrating excellent biocompatibility. This highlights their potential as a promising antibacterial agent to combat multidrug-resistant GNB.