Repurposing a Nonessential Amino Acid γ-Aminobutyric Acid To Treat Multidrug-Resistant Bacteria

The ongoing antimicrobial resistance seriously threatens current therapies for infectious diseases and calls for new antibacterial agents. Gold nanoparticles (Au NPs) are particularly attractive in terms of antibacterial therapies, benefiting from their abundant and engineerable surface chemistries. γ-Aminobutyric acid (GABA) is a nonantibiotic nonessential amino acid acting as an inhibitory neurotransmitter in the human body and has numerous health benefits. In this study, we repurposed GABA to combat multidrug-resistant (MDR) bacteria by presenting it on Au NPs. GABA-capped Au NPs (Au_GABA) possessed a broad antibacterial spectrum against both Gram-positive and Gram-negative bacteria, including MDR strains like carbapenem-resistant Enterobacterales (CRE) and methicillin-resistant Staphylococcus aureus (MRSA). The action mechanism of Au_GABA included oxidative damage to nucleic acids, caused by the promotion of intracellular reactive oxygen species (ROS), and influence on the cell membrane, which leads to disturbances in bacterial metabolism, transport, and biosynthesis. In vivo studies demonstrated the excellent therapeutic efficacy of Au_GABA in MDR bacteria-induced purulent subcutaneous infections. Our study provided a new candidate for the treatment of MDR bacterial infections and a new direction for the novel uses of amino acids.