Silver potentiates aminoglycoside toxicity by enhancing their uptake
Marion Herisse, Yohann Duverger, Isabelle Martin-Verstraete, Frederic Barras, Benjamin Ezraty
MOLECULAR MICROBIOLOGY | WILEY | Published : 2017
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..View full abstract
Awarded by Agence Nationale Recherche (ANR)
We thank members of the FB group for comments on the manuscript and advices and discussions throughout the work. We are grateful to the referees for insightful criticisms and comments. We are grateful to E. Bouveret (LISM, Marseille) and to T.P. Stinear (University of Melbourne, Australia) for critical reading the manuscript and providing feedback. M. H. was supported by the Fondation pour la Recherche Medicale (FRM). This work was supported by grants from Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) and Agence Nationale Recherche (ANR) (# ANR-15- JAMR-0003-02 Combinatorial).