Structure–Activity Relationship of Membrane-Targeting Cationic Ligands on a Silver Nanoparticle Surface in an Antibiotic-Resistant Antibacterial and Antibiofilm Activity Assay

To explore the structure-activity relationship of membrane-targeting cationic ligands on a silver nanoparticle surface in an antibiotic-resistant antibacterial and antibiofilm activity assay, a series of functionalized silver nanocomposites were synthesized. Tuning the structural configuration, molecular weight, and side-chain length of the cationic ligands on the nanoparticle surface provided silver nanocomposites with effective antibacterial activity against both antibiotic-resistant Gram-negative and Gram-positive bacteria, including bacterial biofilms. These silver nanocomposites did not trigger hemolytic activity. Significantly, the bacteria did not develop resistance to the obtained nanocomposites even after 30 generations. A study of the antibacterial mechanism confirmed that these nanocomposites could irreversibly disrupt the membrane structure of bacteria and effectively inhibit intracellular enzyme activity, ultimately leading to bacterial death. The silver nanocomposites (64 μg/mL) could eradicate 80% of an established antibiotic-resistant bacterial biofilm. The strong structure-activity relationship toward antibacterial and antibiofilm activity suggests that variations in the conformational property of the functional ligand could be valuable in the discovery of new nano-antibacterial agents for treating pathogenic bacterial infections.