3月6日,PLoS Biology发表了希伯来大学哈达萨医学院的研究人员的一项研究成果,首次描述了在细菌中一种与更高等生物凋亡类似的新的细胞死亡途径。
研究人员还发现,这种新的类凋亡死亡(apoptotic-like death, ALD)通过mazEF毒素-抗毒素系统的调节而受到另外一种非凋亡的程式化细胞死亡(programmed cell death, PCD)的抑制。
研究人员对在E. coli中所发现的两种极具差异的死亡路径感到惊讶。这种新发现的细菌细胞死亡系统具有多个与多细胞真核生物细胞凋亡相同的特征,故而被命名为类凋亡死亡(apoptotic-like death, ALD)。特别是在真核生物细胞凋亡和ALD中,细胞DNA均变称碎片,细胞膜被去极化,这可以通过细胞内的荧光染料来检测。当细胞DNA发生严重损伤时,这种新发现的ALD路径通过mazEF系统调节而被PCD路径抑制。
细菌选用何种死亡途径有何影响?该问题的答案可能对利他进化具有启示意义。mazEF系统取决于细胞浓度,这可以确保在生存条件恶劣时足够的细菌死亡从而提供大量细菌原材料供那些存活的细菌利用。而ALD路径则相反,并不取决于浓度,可能是在mazEF系统失效时发挥后备系统的作用。
研究人员进一步的研究是,阐明真核生物细胞凋亡与细菌细胞凋亡之间的相似性,以及凋亡性死亡的进化起源。ALD像是传统mazEF利他死亡途径的一个非利他后备死亡路径:若mazEF路径中的某个组分失活,细菌死亡则通过ALD来发生。进一步的实验将有助揭开ALD的分子机制,并帮助了解这种系统是否实际上对“群体利益优先”的种群反应起到影响。(生物谷Bioon.com)
doi:10.1371/journal.pbio.1001281
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Two Programmed Cell Death Systems in Escherichia coli: An Apoptotic-Like Death Is Inhibited by the mazEF-Mediated Death Pathway
Ariel Erental, Idith Sharon, Hanna Engelberg-Kulka
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.