Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
PLoS Biol. 2012;10(3):e1001281. doi: 10.1371/journal.pbio.1001281. Epub 2012 Mar 6.
In eukaryotes, the classical form of programmed cell death (PCD) is apoptosis, which has as its specific characteristics DNA fragmentation and membrane depolarization. In Escherichia coli a different PCD system has been reported. It is mediated by the toxin-antitoxin system module mazEF. The E. coli mazEF module is one of the most thoroughly studied toxin-antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF. mazEF-mediated cell death is a population phenomenon requiring the quorum-sensing pentapeptide NNWNN designated Extracellular Death Factor (EDF). mazEF is triggered by several stressful conditions, including severe damage to the DNA. Here, using confocal microscopy and FACS analysis, we show that under conditions of severe DNA damage, the triggered mazEF-mediated cell death pathway leads to the inhibition of a second cell death pathway. The latter is an apoptotic-like death (ALD); ALD is mediated by recA and lexA. The mazEF-mediated pathway reduces recA mRNA levels. Based on these results, we offer a molecular model for the maintenance of an altruistic characteristic in cell populations. In our model, the ALD pathway is inhibited by the altruistic EDF-mazEF-mediated death pathway.
在真核生物中，经典的程序性细胞死亡（PCD）形式是细胞凋亡，其特征是 DNA 片段化和膜去极化。在大肠杆菌中，已经报道了一种不同的 PCD 系统。它是由毒素-抗毒素系统模块 mazEF 介导的。大肠杆菌 mazEF 模块是研究最透彻的毒素-抗毒素系统之一。mazF 编码一种稳定的毒素 MazF，而 mazE 编码一种不稳定的抗毒素 MazE，它可以防止 MazF 的致死作用。mazEF 介导的细胞死亡是一种群体现象，需要由五肽 NNWNN 指定的群体感应外死亡因子（EDF）。mazEF 由多种应激条件触发，包括 DNA 严重损伤。在这里，我们使用共聚焦显微镜和 FACS 分析表明，在严重的 DNA 损伤条件下，触发的 mazEF 介导的细胞死亡途径导致第二种细胞死亡途径的抑制。后者是一种类似凋亡的死亡（ALD）；ALD 是由 recA 和 lexA 介导的。mazEF 介导的途径降低了 recA mRNA 水平。基于这些结果，我们提出了一个分子模型，用于维持细胞群体中的利他特征。在我们的模型中，ALD 途径被利他的 EDF-mazEF 介导的死亡途径所抑制。
