Elimination of Multidrug-Resistant Bacteria by Transition Metal Dichalcogenides Encapsulated by Synthetic Single-Stranded DNA.

Abstract

Antibiotic-resistant bacteria are a significant and growing threat to human health. Recently, two-dimensional (2D) nanomaterials have shown antimicrobial activity and have the potential to be used as new approaches to treating antibiotic resistant bacteria. In this Research Article, we exfoliate transition metal dichalcogenide (TMDC) nanosheets using synthetic single-stranded DNA (ssDNA) sequences, and demonstrate the broad-spectrum antibacterial activity of MoSe2 encapsulated by the T20 ssDNA sequence in eliminating several multidrug-resistant (MDR) bacteria. The MoSe2/T20 is able to eradicate Gram-positive Escherichia coli and Gram-positive Staphylococcus aureus at much lower concentrations than graphene-based nanomaterials. Eradication of MDR strains of methicillin-resistant S. aureus (MRSA), Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii are shown to occur at at 75 μg mL-1 concentration of MoSe2/T20, and E. coli at 150 μg mL-1. Molecular dynamics simulations show that the thymine bases in the T20 sequence lie flat on the MoSe2 surface and can, thus, form a very good conformal coating and allow the MoSe2 to act as a sharp nanoknife. Electron microscopy shows the MoSe2 nanosheets cutting through the cell membranes, resulting in significant cellular damage and the formation of interior voids. Further assays show the change in membrane potential and reactive oxygen species (ROS) formation as mechanisms of antimicrobial activity of MoSe2/T20. The cellular death pathways are also examined by mRNA expression. This work shows that biocompatible TMDCs, specifically MoSe2/T20, is a potent antimicrobial agent against MDR bacteria and has potential for clinical settings.