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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.Curre