title: The communication factor EDF and the toxin-antitoxin module mazEF determine the mode of action of antibiotics.
abstract: It was recently reported that the production of Reactive Oxygen Species (ROS) is a common mechanism of cell death induced by bactericidal antibiotics. Here we show that triggering the Escherichia coli chromosomal toxin-antitoxin system mazEF is an additional determinant in the mode of action of some antibiotics. We treated E. coli cultures by antibiotics belonging to one of two groups: (i) Inhibitors of transcription and/or translation, and (ii) DNA damaging. We found that antibiotics of both groups caused: (i) mazEF-mediated cell death, and (ii) the production of ROS through MazF action. However, only antibiotics of the first group caused mazEF-mediated cell death that is ROS-dependent, whereas those of the second group caused mazEF-mediated cell death by an ROS-independent pathway. Furthermore, our results showed that the mode of action of antibiotics was determined by the ability of E. coli cells to communicate through the signaling molecule Extracellular Death Factor (EDF) participating in mazEF induction.
authors.affiliation: Department of Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Kolodkin-Gal
authors.forename: Boaz
authors.initials: B
authors.lastname: Sat
authors.forename: Alex
authors.initials: A
authors.lastname: Keshet
authors.forename: Hanna
authors.initials: H
authors.lastname: Engelberg-Kulka
mesh_terms: D000693:Anaerobiosis; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000502:physiology*; D004722:Endoribonucleases / Q000502:physiology*; D004926:Escherichia coli / Q000187:drug effects*; D029968:Escherichia coli Proteins / Q000502:physiology*; D009268:Nalidixic Acid / Q000494:pharmacology; D009842:Oligopeptides / Q000502:physiology*; D014176:Protein Biosynthesis / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012293:Rifampin / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C422954:MazE protein, E coli; C422955:MazF protein, E coli; D009842:Oligopeptides; D017382:Reactive Oxygen Species; C528802:asparagyl-aspargyl-tryptophyl-asparagyl-asparagine; D009268:Nalidixic Acid; D002374:Catalase; D004722:Endoribonucleases; D012293:Rifampin