Polarized Chlamydial Cell Division in the Absence of FtsZ

FtsZ 缺失情况下的极化衣原体细胞分裂

• 批准号: 10249151
• 负责人: Scot P Ouellette
• 金额: $ 32.05万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249151
• 关键词: Actins; Address; Adult; Antibiotics; Asthma; Atherosclerosis; Bacteria; Biological Models; Blindness; Cell division; Cells; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Chlamydophila pneumoniae; Chronic; Communities; Cytoskeletal Proteins; Data; Developed Countries; Developing Countries; Development; Disease; Drug Design; Escherichia coli; Genes; Genome; Growth; Healthcare Systems; Homologous Gene; Human; Knowledge; Lead; Metabolic; Microbiology; Morbidity - disease rate; Pathway interactions; Pelvic Inflammatory Disease; Pneumonia; Process; Proteins; Reiter Disease; Respiratory Tract Infections; Rod; Role; Series; Sexually Transmitted Diseases; Shapes; Site; Trachoma; Tubulin; Work; Yeasts; daughter cell; experimental study; human microbiota; human pathogen; normal microbiota; pathogenic bacteria; public health relevance; trait; tubal infertility

Project Summary: Polarized Chlamydial Cell Division in the Absence of FtsZ Chlamydia is an obligate intracellular bacterial pathogen that causes a range of serious diseases in humans. In developed countries, Chlamydia trachomatis is the primary cause of bacterial sexually transmitted infections (STI) whereas Chlamydia pneumoniae causes community-acquired respiratory infections. In developing countries, C. trachomatis is not only a significant cause of STI, it is also responsible for the primary cause of infectious preventable blindness, trachoma. The major concern of chlamydial infections is that they are often asymptomatic and undiagnosed, which can lead to chronic sequelae. These include pelvic inflammatory disease, tubal factor infertility, and reactive arthritis for C. trachomatis and possibly atherosclerosis and adult onset asthma for C. pneumoniae. Consequently, chlamydial diseases remain a significant burden on health care systems around the world. In adapting to obligate intracellular growth, Chlamydia has significantly reduced its genome size and eliminated genes from various pathways as it relies on the host cell for its metabolic needs. This is a common trait amongst bacteria that evolve to obligate intracellular growth. However, Chlamydia has also lost genes that are considered essential in other bacteria. This proposal outlines a series of studies to investigate the essential process of chlamydial cell division. Chlamydia lacks the gene ftsZ, which encodes the bacterial tubulin-like homolog that is critical for organizing the cell division machinery at the site of division. Thus, how Chlamydia divides is an intriguing microbiological question. We have previously proposed that Chlamydia has substituted the bacterial actin-like homolog MreB for the function of FtsZ. This is unusual for many reasons, one of which is that MreB is important in imparting the rod shape to certain types of bacteria such as E. coli. Chlamydia is a round, coccoid bacterium yet encodes multiple rod-shape determining proteins. Recent evidence from our lab and others suggests that Chlamydia uses these proteins for cell division. Yet, the assumption has been that Chlamydia still utilizes the classic binary fission mechanism to separate daughter cells. Rather, new data from our labs have revealed that Chlamydia uses a polarized budding mechanism similar to yeast to accomplish division. Budding is rare in bacteria, and we intend to use Chlamydia as a model system to understand how budding occurs. We propose a series of experiments to understand the role of bacterial cytoskeletal proteins in bacterial budding as well as how they are regulated and with what other proteins they interact. Because budding is rare, any unique targets represent ideal candidates for anti-chlamydial antibiotic development that would have limited effects on normal flora.

项目摘要：在FtsZ缺乏的情况下，极化衣原体细胞分裂 衣原体是一种专性细胞内细菌病原体，可导致一系列严重的疾病， 人类在发达国家，沙眼衣原体是细菌性传播疾病的主要原因。 传播性感染（STI），而肺炎衣原体导致社区获得性呼吸道感染 感染.在发展中国家，C.沙眼不仅是性传播感染的重要原因， 传染性可预防性失明的主要原因，沙眼。衣原体的主要问题 感染的另一个重要原因是，它们往往没有症状，无法确诊，这可能导致慢性后遗症。这些 包括盆腔炎、输卵管因素不孕症和C反应性关节炎。沙眼衣原体和 可能是动脉粥样硬化和成人哮喘。肺炎。因此，衣原体疾病 仍然是世界各地卫生保健系统的重大负担。 在适应专性细胞内生长的过程中，衣原体显著减小了其基因组大小， 消除了各种途径的基因，因为它依赖于宿主细胞的代谢需要。这是一 细菌进化为专性细胞内生长的共同特征。然而，衣原体也 在其他细菌中被认为是必需的基因丢失。该提案概述了一系列研究， 探讨衣原体细胞分裂的基本过程。衣原体缺乏ftsZ基因， 细菌微管蛋白样同源物，对组织细胞分裂机制至关重要， 师.因此，衣原体如何分裂是一个有趣的微生物学问题。我们先前已经 提出衣原体已经取代了FtsZ功能的细菌肌动蛋白样同源物MreB。这 是不寻常的原因有很多，其中之一是，MreB是重要的，在赋予杆的形状，以某些 细菌如E.杆菌衣原体是一种圆形的球形细菌，但编码多个杆状 决定蛋白质。我们实验室和其他实验室的最新证据表明，衣原体利用这些蛋白质 for cell细胞division分裂.然而，人们的假设是衣原体仍然利用经典的二元裂变 分离子细胞的机制。相反，我们实验室的新数据显示，衣原体使用一种 类似于酵母的极化出芽机制来完成分裂。细菌很少发芽，我们 打算使用衣原体作为模型系统，以了解如何萌芽发生。我们提出了一系列 实验来了解细菌细胞骨架蛋白在细菌出芽中的作用，以及它们如何 以及它们与其他蛋白质的相互作用。因为萌芽很罕见，任何独特的目标 代表了抗衣原体抗生素开发的理想候选物， 正常植物群。