Fe-S Cluster Biosynthesis Controls Uptake of Aminoglycosides in a ROS-Less Death Pathway
Autor: | Laurent Loiseau, Leon Espinosa, Allison Huguenot, Béatrice Py, Athanasios Typas, Frédéric Barras, Yohann Duverger, Alexandra Vergnes, Shu-Yi Su, Benjamin Ezraty, Ana Rita Brochado, Manuel Banzhaf |
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Přispěvatelé: | Laboratoire de chimie bactérienne (LCB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
Iron-Sulfur Proteins
medicine.drug_class Iron [SDV]Life Sciences [q-bio] Antibiotics chemistry.chemical_compound Biosynthesis Drug Resistance Bacterial Escherichia coli medicine Respiratory system chemistry.chemical_classification Reactive oxygen species Electron Transport Complex I Multidisciplinary Chemiosmosis Chemistry Electron Transport Complex II Escherichia coli Proteins Aminoglycoside Anti-Bacterial Agents Aminoglycosides Biochemistry Fenton chemistry Ampicillin Gentamicins Carrier Proteins Reactive Oxygen Species |
Zdroj: | Science Science, 2013, 340 (6140), pp.1583-1587. ⟨10.1126/science.1238328⟩ |
ISSN: | 0036-8075 1095-9203 |
DOI: | 10.1126/science.1238328⟩ |
Popis: | Unreactive Death A controversial proposal that all bactericidal antibiotics kill by reactive oxygen species (ROS) and not by their primary cell target has recently attracted high-profile refutations. The ROS-death pathway implicated overstimulation of the electron transport in respiratory chains; a malfunction that leads to ROS releasing Fe from Fe-S clusters and causing cell death via Fenton chemistry. Ezraty et al. (p. 1583 ) show that electron transport chains and Fe-S clusters are key to killing by aminoglycoside antibiotics but not for the reasons envisioned in the ROS theory. Fe-S clusters are essential for killing because they mature the respiratory chains that produce the necessary proton motive force for the energized uptake of aminoglycosides. Consequently, iron chelators protect against aminoglycosides, not because they scavenge the iron from Fenton chemistry, but because they block aminoglycoside uptake. |
Databáze: | OpenAIRE |
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