the communication factor edf and the toxin–antitoxin module mazef determine the mode of action of antibiotics沟通因素edf和toxin-antitoxin模块mazef确定抗生素的作用方式.pdfVIP

PLoS BIOLOGY The Communication Factor EDF and the Toxin–Antitoxin Module mazEF Determine the Mode of Action of Antibiotics * Ilana Kolodkin-Gal, Boaz Sat, Alex Keshet, Hanna Engelberg- Kulka Department of Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel 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. Citation: Kolodkin-Gal I, Sat B, Keshet A, Engelberg- Kulka H (2008) The communication factor EDF and the toxin–antitoxin module mazEF determine the mode of action of antibiotics. PLoS Biol 6(12): e319. doi:10.1371/journal.pbio.0060319 Introduction conditions can be caused by antibiotics, including (i) those