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Building the segrosome a nucleoprotein machine that drives bacterial DNA segregation

构建 Segrosome 驱动细菌 DNA 分离的核蛋白机器

基本信息

批准号：
BB/G003114/1
负责人：
Finbarr Hayes
金额：
$ 54.35万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FG003114%2F1
关键词：
Building segrosome nucleoprotein machine drives

项目摘要

Genetic information in bacterial cells principally is carried by the chromosome. However, accessory DNA elements known as plasmids can provide added genetic flexibility to the cell, for example, by permitting survival and growth in otherwise hostile environments, such as an antibiotic containing niche. Plasmids often are highly mobile between cells and can be disseminated efficiently in bacterial populations. This partly explains the rapid rise of antibiotic resistant bacteria that is now acutely problematic in clinical environments. Following bacterial chromosome and plasmid DNA replication, it is crucial that both new daughter cells acquire an intact copy of all of the genetic information at cell division. Dedicated molecular mechanisms have evolved to ensure this transmission. We are interested in understanding how precise DNA segregation occurs using genes, the proteins that they encode, and accompanying DNA sequences identified on a multidrug resistance plasmid in the model bacterium, Escherichia coli. Here we propose to employ a variety of genetic and biochemical experimental strategies with the goal of understanding how the proteins involved in segregation of this plasmid arrange into a complex on a specific plasmid DNA sequence as a first stage in the segregation process. Improving our understanding of how bacterial DNA segregation occurs ultimately could lead to the identification of new antibacterial agents that target this crucial process.

细菌细胞中的遗传信息主要由染色体携带。然而，被称为质粒的辅助DNA元件可以为细胞提供额外的遗传灵活性，例如，通过允许在其他不利的环境中存活和生长，例如含有抗生素的生态位。质粒在细胞之间通常是高度移动的，并且可以在细菌群体中有效地散布。这在一定程度上解释了抗生素耐药性细菌的快速上升，这在临床环境中是一个严重的问题。在细菌染色体和质粒DNA复制之后，两个新的子细胞在细胞分裂时获得所有遗传信息的完整拷贝至关重要。专门的分子机制已经发展，以确保这种传输。我们有兴趣了解如何使用基因，它们编码的蛋白质，以及在模型细菌大肠杆菌中的多药耐药质粒上鉴定的伴随DNA序列进行精确的DNA分离。在这里，我们建议采用各种遗传和生物化学实验策略的目的是了解如何参与分离这种质粒的蛋白质排列成一个复杂的特定质粒DNA序列作为第一阶段的分离过程。提高我们对细菌DNA分离如何发生的理解，最终可能导致识别针对这一关键过程的新抗菌剂。