Functional Analysis of the Clp Protease Systems in Chlamydial Growth and Differentiation

项目概述：衣原体生长和发育中Clp蛋白酶系统的功能分析 分化 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性传播的首要原因 感染（STI）。事实上，疾病控制中心最近的报告强调了 衣原体感染率一直超过所有其他类型。在发展中国家，C. 沙眼不仅是性传播感染的重要原因，而且也是传染性疾病的主要原因。 可预防的失明沙眼衣原体感染的主要问题是， 无症状和未确诊，可导致慢性后遗症。这些包括盆腔炎 疾病、输卵管因素不孕和反应性关节炎。沙眼因此，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。这种病原体 在正常生长过程中也适应于在不同的功能和形态形式之间交替， 也被称为其发展周期。这些观察结果，结合其专性细胞内 依赖性，使得衣原体成为一种难以与之合作的有机体。然而，最近的发展 从机制上研究衣原体的遗传工具大大增强了我们对这一点的理解 病原体这项建议将这些新的遗传技术和经典的生物化学技术相结合， 研究以评估保守蛋白酶系统在衣原体生长和发病机制中的作用。的 这项工作的假设是衣原体使用两个独立的蛋白酶系统来调节其生长 以及在发育形式之间的过渡以及对压力的反应。提案的主要目标 包括（i）在体外和体内表征不同蛋白酶系统的功能和（ii） 鉴定和验证这些蛋白酶系统的底物。研究结果将促进我们对 这一重要的病原体，并导致新的治疗药物的设计，是特异性的衣原体。 这反过来又将允许对接受这种高度流行的真菌治疗的患者的正常植物群的影响最小化。 疾病

Project Summary: Functional analysis of the Clp Protease Systems in Chlamydial Growth and Differentiation 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). Indeed, recent reports from the Centers for Disease Control highlight the increasing incidence of STIs, with chlamydia infections consistently outpacing all other types. In developing countries, C. trachomatis is not only a significant cause of STI, but 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. 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 pathogen has also adapted to alternate between different functional and morphological forms during its normal growth, also referred to as its developmental cycle. These observations, combined with its obligate intracellular dependence, makes Chlamydia a difficult organism with which to work. However, recent development of genetic tools to study chlamydiae mechanistically have significantly enhanced our understanding of this pathogen. This proposal applies a combination of these new genetic techniques and classical biochemical studies to evaluate the role of conserved protease systems in chlamydial growth and pathogenesis. The hypothesis of the proposed work is that Chlamydia uses two separate protease systems to regulate its growth and transition between developmental forms as well as to respond to stress. Major goals of the proposal include (i) characterizing the function of the different protease systems both in vitro and in vivo and (ii) identifying and validating substrates of these protease systems. Results will advance our understanding of this important pathogen and lead to the design of novel therapeutic agents that are specific for Chlamydia. This in turn will allow for minimal effects on normal flora for patients receiving treatment for this highly prevalent disease.