Abstract

Drug-resistant bacterial infections pose a serious threat to human health; thus, there is an increasingly growing demand for nonantibiotic strategies to overcome drug resistance in bacterial infections. Mild photothermal therapy (PTT), as an attractive antibacterial strategy, shows great potential application due to its good biocompatibility and ability to circumvent drug resistance. However, its efficiency is limited by the heat resistance of bacteria. Herein, Cu2O@MoS2, a nanocomposite, was constructed by the in situ growth of Cu2O nanoparticles (NPs) on the surface of MoS2 nanosheets, which provided a controllable photothermal therapeutic effect of MoS2 and the intrinsic catalytic properties of Cu2O NPs, achieving a synergistic effect to eradicate multidrug-resistant bacteria. Transcriptome sequencing (RNA-seq) results revealed that the antibacterial process was related to disrupting the membrane transport system, phosphorelay signal transduction system, oxidative stress response system, as well as the heat response system. Animal experiments indicated that Cu2O@MoS2 could effectively treat wounds infected with methicillin-resistant Staphylococcus aureus. In addition, satisfactory biocompatibility made Cu2O@MoS2 a promising antibacterial agent. Overall, our results highlight the Cu2O@MoS2 nanocomposite as a promising solution to combating resistant bacteria without inducing the evolution of antimicrobial resistance.