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：在没有FTSZ的情况下极化衣原体细胞分裂 衣原体是一种义务的细胞内细菌病原体，会导致一系列严重疾病 人类。在发达国家，沙眼衣原体是细菌性的主要原因 传播感染（STI），而衣原体肺炎会引起社区获得的呼吸道 感染。在发展中国家，沙眼梭状芽孢杆菌不仅是STI的重要原因，而且还负责 是导致感染性预防失明的主要原因。衣原体的主要关注点 感染是它们通常无症状且未被诊断，这会导致慢性后遗症。这些 包括盆腔炎症性疾病，输卵管因子不育症以及沙眼梭状芽胞庭的反应性关节炎和反应性关节炎 可能是肺炎梭状芽胞杆菌的动脉粥样硬化和成年哮喘。因此，衣原体疾病 在世界各地的医疗保健系统上仍然承担重大负担。 为了适应义务细胞内生长，衣原体大大降低了其基因组大小和 从各种途径中消除了基因，因为它依靠宿主细胞来代谢需求。这是一个 细菌之间的常见特征，这些特征发展为强迫细胞内生长。但是，衣原体也有 在其他细菌中被认为是必不可少的基因。该提议概述了一系列研究 研究衣原体细胞分裂的基本过程。衣原体缺少编码的基因FTSZ 细菌微管蛋白样同源物对于组织细胞分裂机制至关重要 分配。因此，衣原体如何分裂是一个有趣的微生物问题。我们以前有 建议衣原体取代细菌肌动蛋白样同源物MREB来ftsz的功能。这 由于许多原因是不寻常的，其中之一是MREB对于将杆形状赋予某些 细菌的类型，例如大肠杆菌。衣原体是一种圆形的球菌，但编码多个杆状 确定蛋白质。我们实验室和其他人的最新证据表明，衣原体使用这些蛋白质 用于细胞分裂。然而，假设衣原体仍然使用经典的二进制裂变 分离子细胞的机制。相反，我们实验室的新数据表明，衣原体使用了 两极化的发芽机制类似于酵母，以完成分裂。萌芽在细菌中很少见，我们 打算使用衣原体作为模型系统，以了解出现的发生方式。我们提出了一系列 了解细菌细胞骨架蛋白在细菌萌芽中的作用以及如何 受调节，并与其他蛋白质相互作用。因为萌芽很少见，所以任何独特的目标 代表了抗卫生抗生素开发的理想候选者，对 普通菌群。