3月6日,,PLoS Biology發(fā)表了希伯來大學(xué)哈達(dá)薩醫(yī)學(xué)院的研究人員的一項(xiàng)研究成果,,首次描述了在細(xì)菌中一種與更高等生物凋亡類似的新的細(xì)胞死亡途徑。
研究人員還發(fā)現(xiàn),,這種新的類凋亡死亡(apoptotic-like death, ALD)通過mazEF毒素-抗毒素系統(tǒng)的調(diào)節(jié)而受到另外一種非凋亡的程式化細(xì)胞死亡(programmed cell death, PCD)的抑制,。
研究人員對在E. coli中所發(fā)現(xiàn)的兩種極具差異的死亡路徑感到驚訝。這種新發(fā)現(xiàn)的細(xì)菌細(xì)胞死亡系統(tǒng)具有多個與多細(xì)胞真核生物細(xì)胞凋亡相同的特征,,故而被命名為類凋亡死亡(apoptotic-like death, ALD),。特別是在真核生物細(xì)胞凋亡和ALD中,細(xì)胞DNA均變稱碎片,,細(xì)胞膜被去極化,,這可以通過細(xì)胞內(nèi)的熒光染料來檢測。當(dāng)細(xì)胞DNA發(fā)生嚴(yán)重?fù)p傷時,,這種新發(fā)現(xiàn)的ALD路徑通過mazEF系統(tǒng)調(diào)節(jié)而被PCD路徑抑制,。
細(xì)菌選用何種死亡途徑有何影響?該問題的答案可能對利他進(jìn)化具有啟示意義,。mazEF系統(tǒng)取決于細(xì)胞濃度,,這可以確保在生存條件惡劣時足夠的細(xì)菌死亡從而提供大量細(xì)菌原材料供那些存活的細(xì)菌利用。而ALD路徑則相反,并不取決于濃度,,可能是在mazEF系統(tǒng)失效時發(fā)揮后備系統(tǒng)的作用,。
研究人員進(jìn)一步的研究是,闡明真核生物細(xì)胞凋亡與細(xì)菌細(xì)胞凋亡之間的相似性,,以及凋亡性死亡的進(jìn)化起源,。ALD像是傳統(tǒng)mazEF利他死亡途徑的一個非利他后備死亡路徑:若mazEF路徑中的某個組分失活,細(xì)菌死亡則通過ALD來發(fā)生,。進(jìn)一步的實(shí)驗(yàn)將有助揭開ALD的分子機(jī)制,,并幫助了解這種系統(tǒng)是否實(shí)際上對“群體利益優(yōu)先”的種群反應(yīng)起到影響。(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.