Silver potentiates aminoglycoside toxicity by enhancing their uptake

Marion Herisse (1) , Yohann Duverger (1) , Isabelle Martin-Verstraete (2, 3) , Frédéric Barras (1) , Benjamin Ezraty (1, 4)

1 LCB - Laboratoire de chimie bactérienne
2 PBA (U-Pasteur_6) - Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes
3 UPD7 - Université Paris Diderot - Paris 7
4 IMM - Institut de Microbiologie de la Méditerranée

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.

Mots clés: Adjuvant; Aminoglycoside; Silver; Reactive Oxygen Species; Iron-Sulfur Clusters

Domaines: Génétique; Biologie cellulaire; Biochimie, Biologie Moléculaire; Sciences de l'environnement

Marion Herisse, Yohann Duverger, Isabelle Martin-Verstraete, Frédéric Barras, Benjamin Ezraty. Silver potentiates aminoglycoside toxicity by enhancing their uptake. Molecular Microbiology, 2017, 105 (1), pp.115--126. ⟨10.1111/mmi.13687⟩. ⟨hal-01640020⟩