Premium
Silver potentiates aminoglycoside toxicity by enhancing their uptake
Author(s) -
Herisse Marion,
Duverger Yohann,
MartinVerstraete Isabelle,
Barras Frédéric,
Ezraty Benjamin
Publication year - 2017
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13687
Subject(s) - aminoglycoside , biology , antibiotics , microbiology and biotechnology , gentamicin , escherichia coli , toxicity , kanamycin , mode of action , pharmacology , biochemistry , chemistry , gene , organic chemistry
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.