Kolodkin-Gal Ilana, Sat Boaz, Keshet Alex, Engelberg-Kulka Hanna
Department of Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
PLoS Biol. 2008 Dec 16;6(12):e319. doi: 10.1371/journal.pbio.0060319.
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.
最近有报道称，活性氧（ROS）的产生是杀菌抗生素诱导细胞死亡的常见机制。在此我们表明，触发大肠杆菌染色体毒素-抗毒素系统mazEF是某些抗生素作用模式中的另一个决定因素。我们用属于两组之一的抗生素处理大肠杆菌培养物：（i）转录和/或翻译抑制剂，以及（ii）DNA损伤剂。我们发现两组抗生素都会导致：（i）mazEF介导的细胞死亡，以及（ii）通过MazF作用产生ROS。然而，只有第一组抗生素会导致依赖ROS的mazEF介导的细胞死亡，而第二组抗生素则通过不依赖ROS的途径导致mazEF介导的细胞死亡。此外，我们的结果表明，抗生素的作用模式由大肠杆菌细胞通过参与mazEF诱导的信号分子细胞外死亡因子（EDF）进行通讯的能力决定。
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