Polarized Chlamydial Cell Division in the Absence of FtsZ

项目总结：在没有FtsZ的情况下极化的衣原体细胞分裂 衣原体是一种专性的细胞内细菌病原体，在 人类。在发达国家，沙眼衣原体是细菌性行为的主要原因 传播感染(STI)，而肺炎衣原体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，它也是 沙眼是传染性可预防失明的主要原因。衣原体引起的主要关注 感染通常是无症状和未确诊的，这可能会导致慢性后遗症。这些 包括盆腔炎、输卵管因素不孕以及沙眼衣原体和沙眼衣原体所致反应性关节炎 可能是动脉粥样硬化和成人肺炎衣原体哮喘。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。 在适应细胞内专性生长的过程中，衣原体显著缩小了其基因组大小，并 消除了各种途径的基因，因为它依赖宿主细胞满足其新陈代谢需求。这是一个 细菌进化为细胞内生长的共同特征。然而，衣原体也有 丢失了在其他细菌中被认为必不可少的基因。这项提案概述了一系列研究，以 探讨衣原体细胞分裂的基本过程。衣原体缺乏FtsZ基因，FtsZ编码 细菌微管蛋白类同系物，对组织细胞分裂机制至关重要。 组织。因此，衣原体是如何分裂的是一个有趣的微生物学问题。我们之前已经 提出衣原体取代了细菌肌动蛋白同系物MreB的FtsZ功能。这 有许多原因是不寻常的，其中之一是MreB在赋予杆形的某些方面很重要 细菌的种类，如大肠杆菌。衣原体是一种圆的球状细菌，但编码多个杆状。 测定蛋白质。来自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，人们一直认为衣原体仍然使用经典的二元分裂 分离子代细胞的机制。相反，我们实验室的新数据显示，衣原体使用一种 类似于酵母的极化发芽机制来完成分裂。发芽在细菌中很少见，我们 意愿使用衣原体作为一个模型系统来理解萌芽是如何发生的。我们提出了一系列 了解细菌细胞骨架蛋白在细菌萌发中的作用以及它们如何 是受调控的，以及它们与哪些其他蛋白质相互作用。因为萌芽是罕见的，所以任何独特的目标 是抗衣原体抗生素开发的理想候选者，这种抗生素对 正常的菌群。

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.