The communication factor EDF and the toxin-antitoxin module mazEF determine the mode of action of antibiotics.
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.
Kolodkin-Gal
Ilana
I
Department of Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Sat
Boaz
B
Keshet
Alex
A
Engelberg-Kulka
Hanna
H
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
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