Antibacterial properties of small molecule-functionalized gold nanoparticles against Gram-negative multidrug-resistant bacteria

Abstract:

[Objective] In this study, we investigated the antibacterial properties of 4,6-diamino-2mercaptopyrimidine-functionalized gold nanoparticles (AuNPs) against Gram-negative multidrug-resistant (MDR) bacteria. [Methods] Minimum inhibitory concentration (MIC) of AuNPs against 4 clinically isolated Gram-negative MDR bacteria was determined by the broth dilution method. Time-kill curves within 24 h were drawn by plate counting after treatment with different concentrations of AuNPs. Employing Pseudomonas aeruginosa as a representative strain, the damage of AuNPs to bacterial cell components was studied using laser scanning confocal microscopy, transmission electron microscopy, and gel electrophoresis. The evolution of potential drug resistance of bacteria to AuNPs was evaluated by repeatedly exposed to AuNPs at a sublethal concentration. The biocompatibility of AuNPs to mammalian cells was evaluated by MTT analysis. [Results] The average size of synthesized AuNPs was 6.8 nm, and the zeta potential was +38.4 mV. The AuNPs showed timeand concentration-dependent antibacterial activity against the 4 Gram-negative MDR bacteria, with MIC values ranging from 4 to 8 μg/mL. The AuNPs killed these MDR bacteria through a combined mechanism including cell membrane destruction and DNA damage. No resistance development toward the AuNPs was demonstrated even after continuous passage for 30 d. Preliminary cytotoxicity assay results showed that AuNPs have excellent biocompatibility to mammalian cells, and the survival rate of normal L02 liver cells and normal AT II lung cells is still more than 85% when the concentration reaches 256 μg/mL. [Conclusion] Small molecule-mediated AuNPs have excellent antibacterial activity against Gram-negative MDR bacteria, and potential application value in dealing with severe MDR bacterial infection.