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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.

The Communication Factor EDF and the Toxin–Antitoxin Module mazEF Determine the Mode of Action of Antibiotics