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Activating a Silver Lipoate Nanocluster with a Penicillin Backbone Induces a Synergistic Effect against S. aureus Biofilm
journal contribution
posted on 2019-12-13, 15:37 authored by Humberto H. Lara, David M. Black, Christine Moon, Elizabeth Orr, Priscilla Lopez, Marcos M. Alvarez, Glen Baghdasarian, Jose Lopez-Ribot, Robert L. WhettenMany 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
(Ag29) of known composition (Ag29LA12)[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 IC50 of 2.3 μM, an improvement over
60 times relative to the unconjugated cluster (IC50 = 140
μM). An enhancement of several orders of magnitude over 6-APA
alone (unconjugated) was calculated (IC50 = 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.