Synergy of Nitric Oxide-Releasing Dendrimers and Vancomycin against Gram-positive Pathogenic Biofilms (2015)

Undergraduates: Kelci Schilly, Brittany Worley

Faculty Advisor: Mark Schoenfisch
Department: Chemistry

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The increasing prevalence of antibiotic-resistant bacterial strains has led to a growing demand for antibacterial agents capable of eradicating such bacteria without fostering additional resistance. We have previously demonstrated that nitric oxide-releasing, alkyl chain-modified poly(amidoamine) (PAMAM) dendrimers are effective against both Gram-positive and Gram-negative biofilms, including antibiotic-resistant strains. However, the large concentrations required to eradicate Gram-positive biofilms in particular were often toxic to mammalian cells. As such, we sought to reduce these toxic effects by employing the co-administration of nitric oxide-releasing dendrimers with traditional antibiotics. Herein, we describe the combined effects of the G3 butyl/NO or hexyl/NO PAMAM dendrimers and vancomycin at eradicating Gram-positive Staphylococcus aureus biofilms, including methicillin-resistant strains, to identify any possible synergistic effects. It was observed that both control and nitric oxide-releasing dendrimers demonstrate greater than additive killing with vancomycin against MRSA biofilms, with the addition of nitric oxide release resulting more effective biofilm eradication. Further, the co-administration of G3 hexyl/NO dendrimers and vancomycin resulted in synergistic killing against MRSA biofilms. These results demonstrate the potential of combination therapies in both reducing toxicity to mammalian cells and lessening the development of bacterial resistance.