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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 chimera cluster. To test this hypothesis, the lipoate ligands (LA) of a silver cluster (Ag 29 ) of known composition (Ag 29 LA 12 ) [3-] were covalently conjugated to 6-aminopenicillanic acid, a molecule with a β-lactam backbone. Indeed, the partially conjugated cluster inhibited an Staphylococcus aureus biofilm, in a dose-response manner, with a half-maximal inhibitory concentration IC 50 of 2.3 μM, an improvement over 60 times relative to the unconjugated cluster (IC 50 = 140 μM). An enhancement of several orders of magnitude over 6-APA alone (unconjugated) was calculated (IC 50 = 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.

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