mazEF-mediated programmed cell death network in E. coli

描述（由申请方提供）：程序性细胞死亡（PCD）被定义为导致细胞自杀的主动过程，被认为是多细胞生物体的一种基本机制。1996年，我们报道了第一个染色体毒素-抗毒素系统被发现负责细菌中的PCD。这是大肠杆菌（E. coli）mazEF可调节模块，其中mazF编码稳定的毒素MazF，并且迷宫编码不稳定的抗毒素迷宫，其克服MazF的致死作用。自1996年以来，我们已经取得了相当大的进展，在了解这个系统的遗传，生化，结构和生理特性，以及它与压力条件和一些众所周知的抗生素的作用。在继续这项工作中，在这里，我们建议通过一种新的群体感应细胞外死亡因子（EDF）的全面表征来扩展我们的研究，我们很高兴地发现它是大肠杆菌所需的信号肽分子。coli mazEF介导的细胞死亡。本研究的主要目的如下：1.确定E. coli EDF; 2. 3.阐明EDF与MazEF、E. 4.鉴定EDF受体系统的特性; 5.鉴定除大肠杆菌外细菌的EDF。杆菌EDF及其与细菌死亡的关系的综合研究，我们建议在这里应该有助于了解一个独特的新的群体感应信号分子及其对细菌PCD的重要性。此外，我们的研究结果还有助于阐明细菌通讯的基本生物学现象，从而阐明细菌种群的多细胞行为。实际上，我们的研究结果可能是有用的基础上，为一种新的战略，产生一类新的抗生素，触发细菌PCD，从而帮助什么已经成为一个公共卫生问题。

DESCRIPTION (provided by applicant): Programmed cell death (PCD), defined as an active process which results in cell suicide, is recognized as an essential mechanism in multicellular organisms. In 1996, we reported on the first chromosomal toxin-antitoxin system discovered to be responsible for PCD in bacteria. This was the Escherichia coli (E. coli) mazEF regulateable module in which mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, that overcomes the lethal effect of MazF. Since 1996, we have made considerable progress in understanding the genetic, biochemical, structural and physiological properties of this system, and its relation to stressful conditions and the action of some well known antibiotics. In continuation of this work, here we propose to extend our research by a comprehensive characterization of a novel quorum sensing Extra-cellular Death Factor (EDF) that we were excited to discover as being a signaling peptide molecule required for E. coli mazEF-mediated cell death. Our five specific aims are as follows: 1 to characterize the exact chemical composition of E. coli EDF; 2. to elucidate the mechanism of EDF action; 3.To elucidate the relation of EDF to mazEF and to E. coli other toxin-antitoxin systems; 4.To characterize the EDF receiver(s) system; 5.To characterize EDFs of bacteria other than E. coli. The integrative research on EDF and its relation to bacterial death that we propose here should contribute to the understanding of a unique novel quorum sensing signaling molecule and its importance to bacterial PCD. Moreover, our results should also help to clarify a fundamental biological phenomenon of bacterial communication and thereby the multicellular behavior of bacterial populations. Practically, the results of our study may be useful as a basis for a novel strategy for generating a new class of antibiotics that trigger bacterial PCD, and thereby to help what has become a public health problem.