Silver potentiates aminoglycoside toxicity by enhancing their uptake. Issue 1 (24th April 2017)

• Record Type: Journal Article
• Authors: Herisse, Marion; Duverger, Yohann; Martin‐Verstraete, Isabelle; Barras, Frédéric; Ezraty, Benjamin
• Is Part Of: Molecular microbiology. Volume 105:Issue 1(2017)
• Page Start: 115
• Page End: 126
• Publication Date: 2017-04-24
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13687
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: The predicted shortage in new antibiotics has prompted research for chemicals that could act as adjuvant and enhance efficacy of available antibiotics. In this study, we tested the effects of combining metals with aminoglycosides on Escherichia coli survival. The best synergizing combination resulted from mixing aminoglycosides with silver. Using genetic and aminoglycoside uptake assays, we showed that silver potentiates aminoglycoside action in by‐passing the PMF‐dependent step, but depended upon protein translation. We showed that oxidative stress or Fe–S cluster destabilization were not mandatory factors for silver potentiating action. Last, we showed that silver allows aminoglycosides to kill an E. coli gentamicin resistant mutant as well as the highly recalcitrant anaerobic pathogen Clostridium difficile . Overall this study delineates the molecular basis of silver's potentiating action on aminoglycoside toxicity and shows that use of metals might offer solutions for battling against increased bacterial resistance to antibiotics. Abstract : Silver potentiates aminoglycoside efficiency in by‐passing the PMF‐dependent uptake without ROS contribution. Moreover, we show that silver allows aminoglycoside to kill highly recalcitrant anaerobic pathogen.