Enhanced strategies for cuproptosis‐like death in bacterial infection treatment

Abstract Copper, a classical antibacterial metal, has long been of interest and widely used in medical and public health applications. Recent findings that copper can induce programmed cell death (cuproptosis) not only in eukaryotes but also in bacteria (cuproptosis‐like death) provide a unique perspective for the development of novel antibacterial strategies. On the basis of these findings, current research is actively exploring various strategies to enhance the effects of cuproptosis‐like death, thereby improving its antibacterial efficacy. In this review, we highlight current strategies to enhance cuproptosis‐like death and potential strategies for its development, including aspects of copper transporter protein regulation, exogenous copper ion uptake, the application of nanotechnology, and combination therapy. In addition, we discuss the differences between cuproptosis‐like death and cuproptosis in terms of key events, such as copper homeostasis regulation, lipoylated protein aggregation and iron‒sulfur cluster disruption. Finally, we introduce the limitations and challenges that enhanced bacterial cuproptosis‐like death may face in future studies, which will help to deepen our understanding of the mechanisms of enhanced cuproptosis‐like death.