Combating Bacterial Infection with Metabolism-Regulating Nanomaterials

Abstract: The rise of antibiotic resistance presents a major global health challenge. Bacterial survival is closely tied to their metabolic reprogramming under stress, which enhances their environmental adaptability. While current antibacterial strategies are often limited by bacterial resistance, nanomaterials offer a promising alternative due to their unique physicochemical properties. These functionalized nanoagents can precisely deliver antimicrobials and selectively interfere with metabolic processes of bacteria, including aerobic and anaerobic metabolism, peptidoglycan synthesis, metal ion homeostasis, and nitrogen metabolism. By interfering with energy metabolism, nutrient uptake, and quorum sensing, they can effectively eliminate drug-resistant and persister bacteria. In this review, we summarize the recent advances in metabolic-regulating antibacterial treatment. Then, the clinical translation challenges facing nanotechnology—driven metabolic regulation strategies are discussed. Finally, we hope this review offers forward-looking perspectives on the development of non-antibiotic antibacterial nanoagents for future bacterial metabolic interventions. Keywords: bacterial infection, bacterial metabolism, drug-resistant bacteria, antibacterial nanomaterial