Novel Synthesis of Kanamycin Conjugated Gold Nanoparticles with Potent Antibacterial Activity.

Jason N Payne,Michael G Connor,Sarah Tockstein,William Hamilton,Fenil Chavda,Vivek Badwaik,Harsh Moolani,Matthew B Lawrenz,Hitesh K Waghwani,Rajalingam Dakshinamurthy

doi:10.3389/fmicb.2016.00607

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.

Highlights

Since the discovery of the first antibiotic, Penicillin, in 1928 (National Historic Chemical Landmarks program, 1999) the process of developing mechanisms of resistance against various synthetic antibiotics has been initiated in bacteria
One of the vital steps in the preparation of AuNPs is the addition of chemical agents to reduce the gold ions (Au3+/Au2+) to neutral gold atoms, which results in aggregation upon reaching the saturation limit (Shah et al, 2014)
While continued support for efforts to identify novel antimicrobials is essential to combat these infections, technologies to improve the efficacy of existing antibiotics is an important strategy to compliment the long and expensive process of de novo drug discovery

Summary

Introduction

Since the discovery of the first antibiotic, Penicillin, in 1928 (National Historic Chemical Landmarks program, 1999) the process of developing mechanisms of resistance against various synthetic antibiotics has been initiated in bacteria. This is evident from the presence of various resistant bacterial strains in the early 1930s and 1940s (Clatworthy et al, 2007; “News Feature: A Call to Arms”, 2007). Widespread and irrational use of antibiotics across the globe has led to the emergence of antibiotic resistant strains of bacteria. The rate at which bacteria are developing resistance to existing antibiotics is faster than the development of newer antibiotics (“World Economic Forum – Global Risks 2013 Eighth Edition”, 2014). One of the most widely researched approaches involves the use of metallic and metal-oxide nanoparticles (1–100 nm), such as gold (Au), silver (Ag), and zinc oxide (ZnO) to enhance bactericidal activity (Seil and Webster, 2012; Chernousova and Epple, 2013)

Methods

Results

Conclusion