Wrapping–Trapping versus Extraction Mechanism of Bactericidal Activity of MoS2 Nanosheets against Staphylococcus aureus Bacterial Membrane

The promising broad-spectrum antibacterial activity of two-dimensional molybdenum disulfide (2D MoS2) has been widely recognized in the past decade. However, a comprehensive understanding of how the antibacterial pathways opted by the MoS2 nanosheets varies with change in lipid compositions of different bacterial strains is imperative to harness their full antibacterial potential and remains unexplored thus far. Herein, we present an atomistic molecular dynamics (MD) study to investigate the distinct modes of antibacterial action of MoS2 nanosheets against Staphylococcus aureus (S. aureus) under varying conditions. We observed that the freely dispersed nanosheets readily adhered to the bacterial membrane outer surface and opted for an unconventional surface directed "wrapping-trapping" mechanism at physiological temperature (i.e., 310 K). The adsorbed nanosheets mildly influenced the membrane structure by originating a compact packing of the lipid molecules present in its direct contact. Interestingly, these surface adsorbed nanosheets exhibited extensive phospholipid extraction to their surface, thereby inducing transmembrane water passage analogous to the cellular leakage, even at a slight increment of 20 K in the temperature. The strong van der Waals interactions between lipid fatty acyl tails and MoS2 basal planes were primarily responsible for this destructive phospholipid extraction. In addition, the MoS2 nanosheets bound to an imaginary substrate, controlling their vertical alignment, demonstrated a "nano-knives" action by spontaneously piercing inside the membrane core through their sharp corner, subsequently causing localized lipid ordering in their vicinity. The larger nanosheet produced a more profound deteriorating impact in all of the observed mechanisms. Keeping the existing knowledge about the bactericidal activity of 2D MoS2 in view, our study concludes that their antibacterial activity is strongly governed by the lipid composition of the bacterial membrane and can be intensified either by controlling the nanosheet vertical alignment or by moderately warming up the systems.