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Silver potentiates aminoglycoside toxicity by enhancing their uptake
Marion Herisse1, Yohann Duverger1, Isabelle Martin-Verstraete2,3
1Laboratoire de Chimie Bactérienne, Institut de Microbiologie de la Méditerranée, Aix-Marseille Université, CNRS, UMR 7283, 31 Chemin Joseph Aiguier, 13009, Marseille, France.
Molecular Microbiology
|April 7, 2017
Summary
Silver enhances antibiotic effectiveness against resistant bacteria like E. coli and C. difficile by enabling aminoglycosides to bypass cellular defenses. This metal-based strategy offers new hope against antibiotic resistance.
Area of Science:
- Microbiology
- Infectious Diseases
- Drug Discovery
Background:
- Antibiotic resistance is a growing global health threat.
- There is an urgent need for novel strategies to enhance the efficacy of existing antibiotics.
Purpose of the Study:
- To investigate the potential of combining metals with aminoglycoside antibiotics to combat bacterial infections.
- To elucidate the molecular mechanisms by which silver potentiates aminoglycoside activity.
Main Methods:
- Testing combinations of metals and aminoglycosides against Escherichia coli.
- Utilizing genetic assays and aminoglycoside uptake studies.
- Evaluating efficacy against gentamicin-resistant E. coli and Clostridium difficile.
Main Results:
- Silver demonstrated significant synergy with aminoglycosides against E. coli.
- Silver potentiates aminoglycoside action by bypassing the proton motive force-dependent step, contingent on protein translation.
- This potentiation did not require oxidative stress or Fe-S cluster destabilization.
- Silver-aminoglycoside combinations were effective against a gentamicin-resistant E. coli mutant and Clostridium difficile.
Conclusions:
- Silver's potentiating action on aminoglycoside toxicity is molecularly delineated.
- Metal-adjuvant therapy presents a promising approach to overcome bacterial antibiotic resistance.
- This strategy could provide solutions for treating infections caused by resistant pathogens.