Glucose-Fueled Gold Nanozymes Achieve Picomolar Eradication of Drug-Resistant Staphylococcus aureus

Antimicrobial resistance (AMR) represents a worsening global health emergency, with projections estimating more than 39 million deaths attributable to drug-resistant bacteria by 2050. Diabetic patients face a compounded threat: chronic hyperglycemia suppresses host immunity while enriching wound microenvironments with glucose, accelerating methicillin-resistant Staphylococcus aureus (MRSA) proliferation and rendering conventional antibiotics increasingly ineffective. Here, we report a minimalist, enzyme-free antibacterial strategy based on citrate-stabilized 30 nm gold nanoparticles (AuNPs) that exploit this glucose surplus as a catalytic substrate. Through intrinsic glucose oxidase- and peroxidase-like dual activities, these AuNPs convert ambient glucose and oxygen into a localized cascade of bactericidal reactive oxygen species (ROS), achieving >90% growth inhibition against both methicillin-susceptible S. aureus (MSSA) and MRSA USA300 at concentrations as low as 12.5 pM. Scavenger experiments establish oxidative membrane damage as the primary killing mechanism, and SEM and TEM analyses confirm that AuNPs preferentially accumulate at the bacterial cell membrane, confining ROS production to the site of maximum biological vulnerability. This membrane-localized catalysis, further amplified by brief 532 nm irradiation, accounts for the marked superiority of spherical AuNPs over gold nanorods of comparable composition, demonstrating that spatial localization rather than bulk ROS output governs the killing efficiency. This glucose-fueled, antibiotic-free platform offers a rational strategy for treating drug-resistant infections in hyperglycemic wound environments.