Building the segrosome a nucleoprotein machine that drives bacterial DNA segregation

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元素可以为细胞提供额外的遗传灵活性，例如，通过允许在其他恶劣环境中生存和生长，例如含有抗生素的生态位。质粒通常在细胞之间高度移动，可以在细菌群体中有效地传播。这在一定程度上解释了抗生素耐药细菌的迅速增加，这在临床环境中是一个严重的问题。随着细菌染色体和质粒DNA的复制，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是至关重要的。专门的分子机制已经进化，以确保这种传播。我们感兴趣的是了解精确的DNA分离是如何利用基因、它们编码的蛋白质以及在模型细菌大肠杆菌的多药耐药质粒上鉴定的伴随DNA序列发生的。在这里，我们建议采用各种遗传和生化实验策略，目的是了解参与该质粒分离的蛋白质如何在特定质粒DNA序列上排列成复合体，作为分离过程的第一阶段。提高我们对细菌DNA分离如何发生的理解最终可能导致鉴定针对这一关键过程的新型抗菌剂。

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.