Research ArticleMicrobiology

Silver Enhances Antibiotic Activity Against Gram-Negative Bacteria

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Science Translational Medicine  19 Jun 2013:
Vol. 5, Issue 190, pp. 190ra81
DOI: 10.1126/scitranslmed.3006276

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A Silver Spoon Makes the Medicine Go Down

There is a growing need to enhance our antibacterial arsenal given the rising incidence of antibiotic resistance and the emergence of new virulent pathogens. Drug-resistant, difficult-to-treat Gram-negative bacterial infections have forced clinicians to revisit the use of older antimicrobials that have previously been discarded. Such is the case of silver, an intriguing compound that, despite its long-standing history as an antimicrobial (since 400 B.C.), has an unclear bactericidal mode of action. In their new study, Morones-Ramirez and his colleagues use a systems-based approach to show that silver disrupts multiple bacterial cellular processes, leading to increased production of reactive oxygen species and increased membrane permeability of Gram-negative bacteria. The authors harnessed these effects to potentiate the activity of a broad range of antibiotics against Gram-negative bacteria in different metabolic states, as well as to restore antibiotic susceptibility to resistant bacterial strains. They show both in vitro and in vivo that (i) silver’s ability to induce oxidative stress can be harnessed to potentiate antibiotic activity; (ii) silver sensitizes Gram-negative bacteria to the Gram-positive–specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug; and (iii) silver enhances antibiotic activity against bacterial persister cells and biofilms. This new study provides a way to enhance the activity of existing antimicrobials and goes some way toward enlarging the dwindling armamentarium of drugs to fight bacterial diseases.