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© Bruno Dupuy, Claire Morvan, Institut Pasteur
Cellules végétative et spores de Clostridioides difficile / Vegative cells and spores of Clostridioides difficile
Publication : Molecular microbiology

Silver potentiates aminoglycoside toxicity by enhancing their uptake

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Molecular microbiology - 24 Apr 2017

Herisse M, Duverger Y, Martin-Verstraete I, Barras F, Ezraty B

Link to Pubmed [PMID] – 28383153

Mol. Microbiol. 2017 07;105(1):115-126

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.

https://www.ncbi.nlm.nih.gov/pubmed/28383153