Activating a Silver Lipoate Nanocluster with a Penicillin Backbone Induces a Synergistic Effect against Biofilm.

Many antibiotic resistances to penicillin have been reported, making them obsolete against multiresistant bacteria. Because penicillins act by inhibiting cell wall production while silver particles disrupt the cell wall directly, a synergetic effect is anticipated when both modes of action are incorporated into a cluster. To test this hypothesis, the lipoate ligands (LA) of a silver cluster (Ag) of known composition (AgLA) were covalently conjugated to 6-aminopenicillanic acid, a molecule with a β-lactam backbone. Indeed, the partially conjugated cluster inhibited an biofilm, in a dose-response manner, with a half-maximal inhibitory concentration IC of 2.3 μM, an improvement over 60 times relative to the unconjugated cluster (IC = 140 μM). An enhancement of several orders of magnitude over 6-APA alone (unconjugated) was calculated (IC = 10 000 μM). Cell wall damage is documented via scanning electron microscopy. A synergistic effect of the conjugate was calculated by the combination index method described by Chou-Talalay. This hybrid nanoantibiotic opens a new front against multidrug-resistant pathogens.