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：缺乏 FtsZ 时的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，可引起一系列严重疾病 人类。在发达国家，沙眼衣原体是细菌性性病的主要原因 传播感染（STI），而肺炎衣原体则引起社区获得性呼吸道感染 感染。在发展中国家，沙眼衣原体不仅是性传播感染的重要原因，而且还负责 传染性可预防性失明的主要原因是沙眼。衣原体的主要问题 感染的一个重要原因是它们通常无症状且未确诊，这可能导致慢性后遗症。这些 包括盆腔炎、输卵管因素不孕以及沙眼衣原体反应性关节炎和 肺炎衣原体可能导致动脉粥样硬化和成人哮喘。因此，衣原体疾病 仍然是世界各地医疗保健系统的重大负担。 为了适应专性细胞内生长，衣原体显着减小了其基因组大小并 从各种途径中消除基因，因为它依赖宿主细胞来满足其代谢需求。这是一个 进化为强制细胞内生长的细菌的共同特征。然而，衣原体也 丢失了其他细菌中被认为必需的基因。该提案概述了一系列研究 研究衣原体细胞分裂的基本过程。衣原体缺乏 ftsZ 基因，该基因编码 细菌微管蛋白样同系物，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学问题。我们之前有过 提出衣原体用细菌肌动蛋白样同源物 MreB 取代了 FtsZ 的功能。这 其不寻常的原因有很多，其中之一是 MreB 在赋予某些杆形状方面很重要 细菌类型，例如大肠杆菌。衣原体是一种圆形球状细菌，但编码多种杆状细菌 测定蛋白质。我们实验室和其他实验室的最新证据表明衣原体使用这些蛋白质 用于细胞分裂。然而，假设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表明，衣原体使用 类似于酵母的极化出芽机制来完成分裂。细菌中出芽的情况很少见，而我们 打算使用衣原体作为模型系统来了解出芽是如何发生的。我们提出一系列 通过实验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 受到调节以及它们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 代表抗衣原体抗生素开发的理想候选者，其影响有限 正常菌群。