Tetra hydroxy ethyl disulfate disodium: a novel non-resistant antibacterial chelating agent

Abstract

AbstractDiscovery of novel antibacterial drugs is urgently required as common antibiotics have numerous side effects and are becoming less effective due to antibiotic resistance occurrences. Developing a novel class of antibacterial compounds without inducing the prevalence of resistance when used repeatedly against bacterial pathogens is presumably one of the best approaches to overcome this problem. Tetra hydroxy ethyl disulfate disodium (THES) is a novel antibacterial agent, capable of disrupting cell activity without any need for drug influx. In this study, the molecular interaction between THES, Gram-positive, and Gram-negative bacteria was investigated. It was suggested that THES possessed the desirable characteristics of a non-resistant bacterial agent with bactericidal properties. Additionally, the non-resistant characteristics of THES were validated as a novel antibacterial agent. The unique feature of THES was the property of chelation with its strong binding ability to target ligands. This binding played a major role in bacterial peptidoglycan porosity enlargement, resulting in lysis and cell death. The bacterial cell membrane porosity enlargement was confirmed by Scanning Electron Microscopy, Transmission Electron Microscopy, as well as Atomic Force Microscopy. These findings were further supported by the results fromin silicoanalysis which showed that THES formed favorable interactions with peptidoglycan with a binding affinity of −4.7 kcal/mol. The minimum inhibitory concentration value against multidrug-resistant (MDR) bacteria was notably low, between 0.05 - 0.1%. Furthermore, the analysis of resistance over a seven-month course showed thatStaphylococcus aureusdid not develop resistant characteristics to repeated treatment to THES treatment. This study has also shown that bactericidal characteristics can be easily manipulated and modified for more preferable antibacterial activities, whilst yielding desirable pharmacokinetic/pharmacodynamics (PK/PD) properties. There are several advantages of THES as compared to common antibiotics, including its flexibility in the killing capacity of different microbial strains. The simplicity, efficacy, and non-resistant properties of THES make it a promising drug candidate or compound to combat the outbreak of MDR bacteria in the future.