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Genome segregation in bacteria: investigating protein dynamics and mechanisms in the cell at single molecule level

细菌中的基因组分离：在单分子水平上研究细胞中的蛋白质动力学和机制

基本信息

批准号：
2444263
负责人：
金额：
--
依托单位：
University of York
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2444263
关键词：
Genome segregation bacteria investigating protein

项目摘要

Bacterial multidrug resistance is a global burden on human health worldwide.Large, low copy number plasmids responsible for antibiotic resistance haveevolved strategies to ensure their faithful distribution at celldivision. Multidrug resistance plasmids harbour their own survival system, apartition cassette, which ensures an accurate segregation of the plasmids atcell division. When this system malfunctions, the plasmid is not stablyinherited and is ultimately lost causing bacteria to become sensitive toantimicrobials. The multidrug resistance plasmid TP228 replicates at lowcopy number in Escherichia coli. Its partition cassette encodes two proteins:ParF, an ATPase, and ParG, a DNA-binding protein that associates to aspecific site on the plasmid. By using super-resolution microscopy on livecells, we have shown that ParG-plasmid complexes are entrapped within athree-dimensional ParF meshwork that assembles through the volume of thebacterial chromosome. When the ParG protein is defective, the ParG-plasmidcomplex is excluded from the chromosome volume and lost at the followingcell division. We have proposed a Venus flytrap model as a mechanism forplasmid segregation (1).This project will investigate the localization of ParFG-plasmid complexes inthe cell and the dynamics of complex formation at single molecule level toshed light on the mechanistic details underpinning plasmid segregation.

细菌的多重耐药是全球范围内人类健康的一个负担，负责抗生素耐药性的大的、低拷贝数质粒已经进化出策略来确保它们在细胞分裂时的忠实分布。多药耐药质粒有自己的生存系统，即分离盒，它确保了质粒在细胞分裂时的准确分离。当这个系统发生故障时，质粒不能稳定遗传，最终丢失，导致细菌对抗菌剂敏感。多药耐药质粒TP 228在大肠杆菌中以低拷贝数复制。它的分配盒编码两种蛋白质：ParF，一种ATP酶，和ParG，一种DNA结合蛋白，与质粒上的特异性位点结合。通过在活细胞上使用超分辨率显微镜，我们已经表明ParG-质粒复合物被捕获在三维ParF网络中，该网络通过细菌染色体的体积组装。当ParG蛋白有缺陷时，ParG-质粒复合物被排除在染色体体积之外，并在随后的细胞分裂中丢失。我们已经提出了一个捕蝇草模型作为质粒分离的机制（1）。本项目将研究ParFG-质粒复合物在细胞中的定位以及在单分子水平上复合物形成的动力学，以阐明支持质粒分离的机制细节。