Dual-mode regulation of microbial cell membrane permeability for an enhanced microbial cuproptosis-like death pathway

Abstract

Antibiotics are vital for treating microbial infections, but their overuse has led to antibiotic resistance, necessitating new antimicrobial strategies. Nanomaterials with antimicrobial properties were an alternative, like our designed nano-platform CPHG, which consists of PEI-modified graphene oxide and hyaluronic acid-coated copper ion chelated polydopamine. It could affect microbial metabolic activities through mild photothermal stimulation. Additionally, using the sharp, flake-like structure of graphene oxide, this structure could physically disrupt the microbial cell membrane, and change the membrane's permeability, which in turn further enhanced the permeability of the microbial membrane. Membrane damage caused by dual pathways could increase the permeability of the microbial membrane, promoting its absorption of copper ions. The efficiency of photothermal conversion was increased by incorporating copper ions. It also depleted the GSH within microbes, causing lipid peroxidation. Additionally, it induced a toxic stress response in proteins, leading to cuproptosis-like cell death. The CPHG effectively accomplished swift wound recovery in a Staphylococcus aureus-infected murine wound model. Furthermore, the application of this strategy to Escherichia coli and Candida albicans has also demonstrated excellent antibacterial effects. Hence, CPHG demonstrated promising capabilities in exhibiting wide-range antibacterial efficacy and provided a new approach to addressing the issue of antibiotic resistance. Its unique antimicrobial mechanism reduced the risk of microorganisms developing resistance, offering a new direction for future antimicrobial treatments.