Escherichia coli MazF leads to the simultaneous selective synthesis of both "death proteins" and "survival proteins".

Escherichia coli MazF leads to the simultaneous selective synthesis of both "death proteins" and "survival proteins".
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DOI:
10.1371/journal.pgen.1000390
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发表时间:
2009-03
期刊:
影响因子:
4.5
通讯作者:
Engelberg-Kulka H
Engelberg-Kulka H
中科院分区:
生物学2区
文献类型:
--
作者:
Amitai S;Kolodkin-Gal I;Hananya-Meltabashi M;Sacher A;Engelberg-Kulka H

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大肠杆菌MazEF模块是研究最彻底的毒素-抗毒素系统之一。MazF编码稳定的毒素MazF,而迷宫编码不稳定的抗毒素迷宫,其阻止MazF的致死作用。MazF是一种核糖核酸内切酶,通过在ACA序列处切割mRNA来抑制蛋白质合成。在这里,使用二维凝胶,我们表明,在E。在大肠杆菌中,尽管MazF诱导导致大多数蛋白质合成的抑制,但仍然允许合成主要小于约20 kDa的一组专有蛋白质。我们通过质谱鉴定了其中一些小蛋白质。通过从E.大肠杆菌染色体上,我们发现它们是大多数细胞群体死亡所必需的。在诱导MazEF介导的细胞死亡的相同实验条件下,发现其他此类蛋白质是细胞的小亚群存活所需的。因此,MazF似乎是诱导下游途径的调节剂,导致大多数种群的死亡和一小部分亚群的继续存活,当生长条件变得不那么紧张时,这将可能成为新种群的核心。肠道细菌E.和大多数其他细菌一样,大肠杆菌的染色体上携带着一对基因;其中一个基因指定毒素,另一个基因指定抗毒素。以前,我们已经证明,在E。大肠杆菌在压力条件下导致细菌细胞死亡。显然,导致任何给定细胞死亡的系统对该特定细胞不利。另一方面,单个细胞的死亡可能对整个细菌群体有利。在这里,我们第一次报告MazF激活了一个复杂的蛋白质网络。此外,我们还首次表明,MazF影响两个相反的过程:细胞死亡和细胞存活。我们认为,这种双重效应可能提供了一个进化的合理性,为MazEF介导的细胞死亡。当暴露于压力条件下时,大多数细胞群体经历程序性细胞死亡;然而,似乎有一个活跃的过程使一小部分群体存活。当生长条件变得不那么紧张时,可能就是这一小群幸存者成为新细胞群的基础。
The Escherichia 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. MazF is an endoribonuclease that leads to the inhibition of protein synthesis by cleaving mRNAs at ACA sequences. Here, using 2D-gels, we show that in E. coli, although MazF induction leads to the inhibition of the synthesis of most proteins, the synthesis of an exclusive group of proteins, mostly smaller than about 20 kDa, is still permitted. We identified some of those small proteins by mass spectrometry. By deleting the genes encoding those proteins from the E. coli chromosome, we showed that they were required for the death of most of the cellular population. Under the same experimental conditions, which induce mazEF-mediated cell death, other such proteins were found to be required for the survival of a small sub-population of cells. Thus, MazF appears to be a regulator that induces downstream pathways leading to death of most of the population and the continued survival of a small sub-population, which will likely become the nucleus of a new population when growth conditions become less stressful. The enteric bacterium E. coli, as most other bacteria, carries a pair of genes on its chromosome; one of them specifies a toxin and the other one an antitoxin. Previously, we have shown that that the mazEF toxin–antitoxin system in E. coli is responsible for bacterial cell death under stressful conditions. Clearly, a system that causes any given cell to die is not advantageous to that particular cell. On the other hand, the death of an individual cell may be advantageous for the bacterial population as a whole. Here, for the first time, we report that MazF activates a complex network of proteins. Moreover, we also show, for the first time, that MazF affects two opposite processes: cell death and cell survival. We suggest that this dual effect may provide an evolutionary rational for mazEF-mediated cell death. When exposed to stressful conditions, most of the cell population undergoes programmed cell death; however, there appears to be an active process that keeps a small fraction of the population alive. When growth conditions become less stressful, it is probably this small sub-population of survivors that becomes the basis of a new cell population.
细菌程序性细胞死亡和细菌多细胞行为。
DOI: 10.1371/journal.pgen.0020135
发表时间: 2006-10
期刊: PLoS genetics
影响因子: 4.5
作者:
通讯作者: --
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