Fe-S cluster biosynthesis controls uptake of aminoglycosides in a ROS-less death pathway

Research output: Contribution to journalArticlepeer-review


  • Benjamin Ezraty
  • Alexandra Vergnes
  • Yohann Duverger
  • Allison Huguenot
  • Ana Rita Brochado
  • Shu-Yi Su
  • Leon Espinosa
  • Laurent Loiseau
  • Béatrice Py
  • Athanasios Typas
  • Frédéric Barras

Colleges, School and Institutes

External organisations

  • Laboratoire de Chimie Bactérienne, Aix-Marseille Université, CNRS, UMR 7283, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13009 Marseille France.


All bactericidal antibiotics were recently proposed to kill by inducing reactive oxygen species (ROS) production, causing destabilization of iron-sulfur (Fe-S) clusters and generating Fenton chemistry. We find that the ROS response is dispensable upon treatment with bactericidal antibiotics. Furthermore, we demonstrate that Fe-S clusters are required for killing only by aminoglycosides. In contrast to cells, using the major Fe-S cluster biosynthesis machinery, ISC, cells using the alternative machinery, SUF, cannot efficiently mature respiratory complexes I and II, resulting in impendence of the proton motive force (PMF), which is required for bactericidal aminoglycoside uptake. Similarly, during iron limitation, cells become intrinsically resistant to aminoglycosides by switching from ISC to SUF and down-regulating both respiratory complexes. We conclude that Fe-S proteins promote aminoglycoside killing by enabling their uptake.


Original languageEnglish
Pages (from-to)1583-7
Number of pages5
Issue number6140
Publication statusPublished - 28 Jun 2013


  • Aminoglycosides, Ampicillin, Anti-Bacterial Agents, Carrier Proteins, Drug Resistance, Bacterial, Electron Transport Complex I, Electron Transport Complex II, Escherichia coli, Escherichia coli Proteins, Gentamicins, Iron, Iron-Sulfur Proteins, Reactive Oxygen Species, Journal Article, Research Support, Non-U.S. Gov't