Novel Synthesis of Kanamycin Conjugated Gold Nanoparticles with Potent Antibacterial Activity

Abstract

With a sharp increase in the cases of multi-drug resistant (MDR) bacteria all over the world, there is a huge demand to develop a new generation of antibiotic agents to fight them. As an alternative to the traditional drug discovery route, we have designed an effective antibacterial agent by modifying an existing commercial antibiotic, kanamycin, conjugated on the surface of gold nanoparticles (AuNPs). In this study, we report a single-step synthesis of kanamycin-capped AuNPs (Kan-AuNPs) utilizing the combined reducing and capping properties of kanamycin. While Kan-AuNPs have increased toxicity to a primate cell line (Vero 76), antibacterial assays showed dose-dependent broad spectrum activity of Kan-AuNPs against both Gram-positive and Gram-negative bacteria, including Kanamycin resistant bacteria. Further, a significant reduction in the minimum inhibitory concentration (MIC) of Kan-AuNPs was observed when compared to free kanamycin against all the bacterial strains tested. Mechanistic studies using transmission electron microscopy and fluorescence microscopy indicated that at least part of Kan-AuNPs increased efficacy may be through disrupting the bacterial envelope, resulting in the leakage of cytoplasmic content and the death of bacterial cells. Results of this study provide critical information about a novel method for the development of antibiotic capped AuNPs as potent next-generation antibacterial agents.

One‐pot facile synthesis of silk sericin‐capped gold nanoparticles by UVC radiation: Investigation of stability, biocompatibility, and antibacterial activity

“…AuNPs were reported to have intrinsic antibacterial activity against various pathogenic microorganism. So, they were intentionally combined with antibiotics for increasing the efficacy of antibacterial activity (Bhattacharya et al, 2012;Kalita et al, 2016;Payne et al, 2016). Researches about developing new antibacterial agents have focused on colloidal gold nanoparticles since they can penetrate through the outer membrane and the peptidoglycan layer of bacteria and result in the production of reactive oxygen species (ROS) (Zhao & Jiang, 2013).…”

“…It was suggested in another study that the accumulation of the kanamycin conjugated AuNPs within the bacterial membrane and cytosol occurred by virtue of the facilitation of the antibiotic transportation across the bacterial membrane via the AuNPs. In addition, the local concentration of the antibiotic increased compared to antibiotic alone, which eventually resulted in the cell lysis (Payne et al, 2016). The membrane peptidoglycan layer thickness of Gram-positive bacteria is thick and especially, B. subtilis was reported to be a very resistant bacteria and thus able to endure very harsh conditions (Shamaila et al, 2016).…”

“…Especially, to cope with multidrugresistant bacteria, one of the most influential strategies to enhance antibacterial efficacy could be the conjugation of antibiotics with AuNPs. For instance, AuNPs functionalized with various antibiotics, such as amoxicillin (Kalita et al, 2016), streptomycin (Bhattacharya, Saha, Mukherjee, Santra, & Karmakar, 2012), and kanamycin (Payne et al, 2016) were reported to improve the antibacterial activity of the corresponding free antibiotics against various bacteria.…”

Green biosynthesis of gold nanoparticles using Chenopodium formosanum shell extract and analysis of the particles' antibacterial properties

“…36 Another paper reported that the antibacterial mechanism of Au NPs was that these Au NPs accumulated within the bacterial membrane and cytoplasm, and then interacted with the protein synthesis machinery to directly inhibit bacterial growth. 37 Au NPs showed higher activity against Escherichia coli than Staphylococcus aureus. It was the cell wall of the Staphylococcus aureus contains a thick layer of peptidoglycan, forming a more rigid structure leading to difficult penetration of the Au NPs compared to the Escherichia coli.…”

Microbially synthesized nanoparticles as next generation antimicrobials: scope and applications

“…Au-NPs conjugated with an antibiotic, kanamycin, exhibited dose-dependent broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria, including bacteria resistant to kanamycin. It was indicated that the increased efficacy might have resulted due to the damage of the bacterial cell envelope, consequently resulting in the leakage of intracellular components and cell death (Payne et al, 2016).…”