Zinc coordination self-assembly of bacitracin nanoparticles with broadened antibacterial spectrum

Bacitracin has been extensively studied for its antibacterial application due to its excellent anti-Gram-positive bacterial properties. However, its application of conventional bacitracin has been limited because of its limited antibacterial activity against Gram-negative bacteria, especially negative bacilli. In this study, we designed and synthesized bacitracin-zinc nanodrugs (BPNDs) through zinc coordination self-assembly of bacitracin, which exhibit potent antibacterial effects not only against Gram-positive bacterial Staphylococcus aureus but also against Escherichia coli, a typical Gram-negative bacillus. The morphological and antimicrobial properties of the self-assembled BPNDs with different molar ratios of bacitracin to zinc ions were investigated. The bacterial biofilm experiments confirmed the biofilm scavenging effect of BPNDs, further expanding the application of this antimicrobial agent. In-depth cell viability experiments indicated that this antimicrobial activity might be related to the penetration of BPNDs into bacterial cell membranes. This study reveals that the zinc-coordinated peptide self-assembly strategy expands the antibacterial spectrum of conventional bacitracin, making it a potential candidate for novel antimicrobial drugs to address the bacterial resistance dilemma and provide stable alternatives for a wide range of biomedical and related industries.