Personalized design enzyme-like activity theanine coated Pt clusters for catalytic damage of bacterial and infection management

Abstract

The formation of biofilm affords protection against host immune responses while efficiently impeding the infiltration of antibiotics and other therapeutic agents. To address these issues, the development of novel non-antibiotic antimicrobial drugs is emerging as promising solutions for combating infectious diseases. To explore inorganic metal clusters antibiotics, we have designed a theanine platinum cluster (PtCs) antibacterial agent that freely penetrates the cell wall pores to be internalized inside bacteria. This agent exhibits enhanced bioavailability, possesses peroxidase-like activity with efficient singlet oxygen (¹O₂) generation, and inhibits and destroys biofilm formation. The in vitro experimental results demonstrate that PtCs potently inhibit bacterial growth and disrupt biofilms by catalyzing the production of reactive oxygen species (ROS). Additionally, we found that PtCs can trigger bacterial apoptosis by traversing the cell wall to enter the bacterium, where they induce DNA damage and inhibit DNA replication. In vivo study demonstrated that PtCs significantly enhance the healing of multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA) infectious wounds, and rescue mice suffering from MRSA-induced sepsis. The synthesized PtCs represent a promising candidate in the quest to combat bacterial resistance, offering significant potential for the development of novel antimicrobial strategies against bacterial infections