The cell division interactome of Enterococcus faecalis

粪肠球菌细胞分裂相互作用组

• 批准号: 203651-2012
• 负责人: Dillon, JoAnne
• 金额: $ 2.48万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=569983
• 关键词: cell; division; interactome; Enterococcus; faecalis

Enterococcus faecalis (Ef), a bacterium which is an antibiotic resistant "superbug", is widely distributed in nature, colonizing a variety of mammals, birds, reptiles, insects and other organisms. Ef has important societal relevance as a veterinary and human pathogen with the potential to cause serious disease and to spread serious antibiotic resistance to other bacteria. An essential component of Ef cell viability, growth and spread is its ability to divide. Cell division is a complex molecular process initiated by the formation of an FtsZ protein ring at the mid-cell site followed by a cascade of different proteins which interact to form the divisome (cell division interactome). In certain bacteria, FtsZ placement at the mid-cell is directed by proteins named MinC, MinD and MinE. Some bacteria, classified as Gram-positive (Gm+), lack MinE and instead possess a conserved protein called DivIVA. Other Gm+ bacteria, such as Ef, lack any Min proteins but retain DivIVA homologues. Thus, different proteins are used in the cell division process in different bacteria. Using Ef as a model microorganism to study Gm+ coccal cell division, we identified a new conserved protein, MLJD1, which binds DivIVA and which participates in Ef cell division. Disruption of this gene in Ef causes cell death. We also identified important amino acids and structures required for DivIVA functionality. In our present research, we will further investigate the Ef divisome/interactome through microbiological, microscopy, molecular, genetic and biochemical approaches. We will fully define the various interactions between at least 11 Ef cell division proteins, thereby developing the first high quality divisome/interactome map for Ef. We will produce novel insight regarding the basis of the DivIVAEf -MLJD1 interaction, the structure of MLJD1, and the interaction of these proteins with the full range of other cell division proteins. Research on the Ef divisome, and the novel proteins associated with it will produce critical information not only on how this important organism divides, but may identify avenues that may help us to combat this and other antibiotic resistant bacteria.

粪肠球菌（Enterococcus faecalis，Ef）是一种耐抗生素的“超级细菌”，在自然界中广泛分布，在哺乳动物、鸟类、爬行动物、昆虫等多种生物体内定植。EF作为一种兽医和人类病原体具有重要的社会意义，有可能导致严重的疾病并将严重的抗生素耐药性传播给其他细菌。Ef细胞活力、生长和扩散的一个重要组成部分是其分裂能力。细胞分裂是一个复杂的分子过程，由FtsZ蛋白环在细胞中部形成，随后是一系列不同的蛋白质相互作用形成分裂体（细胞分裂相互作用体）。 在某些细菌中，FtsZ在中间细胞的位置由名为MinC，MinD和MinE的蛋白质指导。一些细菌，被归类为革兰氏阳性（Gm+），缺乏MinE，而是拥有一种名为DivIVA的保守蛋白质。其他Gm+细菌，如Ef，缺乏任何Min蛋白，但保留DivIVA同源物。因此，不同的蛋白质用于不同细菌的细胞分裂过程。使用Ef作为模型微生物来研究Gm+球菌细胞分裂，我们鉴定了一种新的保守蛋白MLJD 1，其结合DivIVA并参与Ef细胞分裂。Ef中该基因的破坏导致细胞死亡。我们还确定了DivIVA功能所需的重要氨基酸和结构。在我们目前的研究中，我们将通过微生物，显微镜，分子，遗传和生物化学方法进一步研究Ef分裂体/相互作用体。我们将充分定义至少11个Ef细胞分裂蛋白之间的各种相互作用，从而开发出第一个高质量的分裂体/相互作用组Ef地图。我们将产生关于DivIVAEf -MLJD 1相互作用的基础，MLJD 1的结构，以及这些蛋白质与其他细胞分裂蛋白质的全方位相互作用的新见解。 对Ef分裂体以及与之相关的新型蛋白质的研究不仅将产生关于这种重要生物如何分裂的关键信息，而且可能会发现可能有助于我们对抗这种和其他抗生素耐药细菌的途径。