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© Research
Publication : Science (New York, N.Y.)

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Science (New York, N.Y.) - 28 Jun 2013

Ezraty B, Vergnes A, Banzhaf M, Duverger Y, Huguenot A, Brochado AR, Su SY, Espinosa L, Loiseau L, Py B, Typas A, Barras F

Link to Pubmed [PMID] – 23812717

Science 2013 Jun;340(6140):1583-7

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.

https://www.ncbi.nlm.nih.gov/pubmed/23812717