Novel Antimicrobial Nano Bacteriocin: Lactic Acid Bacteria‐Derived, Self‐Assembled, and Enhanced for Superior Antimicrobial Activity

ABSTRACT As antimicrobial resistance emerges as a critical global health threat, food‐grade bacteriocin, a kind of antimicrobial peptide (AMPs), offers promising new therapies but is hampered by poor stability and water solubility. To address this, we engineered a carrier‐free self‐assembly strategy: a novel bacteriocin from lactic acid bacteria in fermented food was modified to increase its hydrophobicity, enabling spontaneous formation of nano‐antimicrobial bacteriocins (NAMBs) in TSB, LB, and MH media. These NAMBs exhibit a broader antimicrobial spectrum and enhanced potency against both Gram‐positive and Gram‐negative pathogens, including Listeria monocytogenes , Acinetobacter baumannii , and Vibrio parahaemolyticus , as evidenced by markedly reduced minimum inhibitory concentrations in vitro and superior therapeutic efficacy in infected mice in vivo. Mechanistic investigations reveal targeted disruption of cell envelope metabolism: in L. monocytogenes , NAMBs fortify the peptidoglycan layer while depleting wall teichoic acids and lipoteichoic acids, impairing carbohydrate metabolism and membrane transport; in A. baumannii , they downregulate fatty acid synthesis, disorder phospholipid composition, and weaken lipopolysaccharide integrity, culminating in membrane destabilization and cell death. These dual actions—disordering metabolic processes and remodeling bacterial cell walls or membranes—highlight the versatility of NAMBs. Our carrier‐free self‐assembly approach thus overcomes AMP stability and solubility limitations and paves the way for next‐generation antimicrobial therapies.