Gram-selective antibacterial activity of mixed-charge 2D-MoS₂

The development of nanomaterial-based antibiotics can be the most potent alternative due to the increasing resistance against conventional antibiotics. However, one of the important parameters in the development of antibacterial agents is their Gram selectivity, which has been seldomly explored in the case of nano-antibiotics. The multimodal action of surface-functionalized nanomaterials can exhibit strain selectivity and enhanced antibacterial activity. Herein, we designed a Gram-selective antibacterial system based on two-dimensional molybdenum disulphide (2D-MoS₂) functionalized with different proportions of positively and negatively charged ligands. Two representative ESKAPE pathogenic strains, i.e., Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa) were considered to evaluate the selective antibacterial activity. The mechanistic insight behind selectivity was established by evaluating the degree of membrane depolarization together with oxidative stress. The selective generation of intracellular reactive oxygen species (ROS) together with membrane depolarization contributed to the selective killing of the pathogenic bacteria. Gram selectivity was achieved by simply controlling the surface functionality based on the different cell wall compositions and structures of bacterial strains. The interplay between polyvalent electrostatic and non-covalent interactions was mainly responsible for damaging the cell membrane. Furthermore, to establish the antibacterial mechanism, we performed extracellular and intracellular reactive oxidative stress, membrane depolarization and permeabilization assays. In summary, we prepared simple and efficient Gram-selective 2D-MoS₂-based antibacterial agents, which can be extended to other nano-antibiotic systems.