The role of disulfide bonding in type III secretion of Chlamydia spp.

二硫键在衣原体 III 型分泌中的作用。

• 批准号: 8268349
• 负责人: KENNETH A FIELDS
• 金额: $ 19.13万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8268349
• 关键词: Activity Cycles; Acute Disease; Address; Affect; Architecture; Bacteria; Biology; Cell physiology; Chemistry; Chlamydia; Chronic Disease; Complex; Coupled; Cysteine; Development; Dimensions; Disease; Dissection; Disulfides; Event; Gene Expression; Goals; Health; Human; Knowledge; Lead; Link; Mediating; Methods; Modification; Molecular; Molecular Conformation; Morphology; Nature; Needles; Oxidation-Reduction; Pathogenesis; Pattern; Prevalence; Process; Proteins; Reagent; Regulation; Role; Stimulus; Structure; Sulfhydryl Compounds; System; Testing; Time; Type III Secretion System Pathway; United States; Virulence; Work; base; crosslink; cysteine rich protein; design; disulfide bond; disulfide bond reduction; in vitro Assay; in vivo; member; novel; obligate intracellular parasite; particle; pathogen; protein function; research study; socioeconomics

DESCRIPTION (provided by applicant): The Chlamydia genus contains members representing significant health concerns in the United States. A significant burden exists due to prevalence and the combined health and socioeconomic impact of acute and chronic disease. Chlamydiae are obligate intracellular parasites that undergo a complex developmental cycle that is accompanied by distinct alterations in gene expression, morphology, and protein function. For example, expression and activity of the virulence-associated type III secretion system (T3SS) is intimately coupled to developmental progression. In addition, disulfide bond dynamics in the outer envelope of Chlamydia spp. has a dominant, yet incompletely understood, role in the developmental cycle. We have preliminary evidence that T3S proteins participate in developmentally associated alterations in disulfide bonding. We propose a combination of methods designed to characterize disulfide bonding among T3S apparatus proteins to establish the extent, temporal dynamics, and impact on secretion activity. A great deal of emphasis has been placed on identification and characterization of secreted effector proteins while comparatively little is known regarding more direct contributions of the T3S apparatus to chlamydial biology. Although the T3S process displays a significant degree of functional conservation among Gram-negative pathogens, it is likely that the highly unique niche colonized by chlamydiae results in mechanisms novel to the chlamydial system. Therefore, these studies will add a new dimension to knowledge regarding the T3S mechanism, lead to an enhanced understanding of Chlamydia-mediated disease, and potentially yield novel preventative and treatment therapies.

描述（由申请人提供）：衣原体属包含代表美国重大健康问题的成员。由于急性和慢性疾病的流行以及对健康和社会经济的综合影响，存在着巨大的负担。衣原体是专性细胞内寄生虫，经历复杂的发育周期，伴随着基因表达、形态和蛋白质功能的明显改变。例如，毒力相关的 III 型分泌系统 (T3SS) 的表达和活性与发育进程密切相关。此外，衣原体外膜中的二硫键动力学。在发育周期中具有主导但尚未完全理解的作用。我们有初步证据表明 T3S 蛋白参与二硫键的发育相关改变。我们提出了一种旨在表征 T3S 装置蛋白之间二硫键键合的方法组合，以确定其程度、时间动态以及对分泌活性的影响。人们非常重视分泌效应蛋白的鉴定和表征，而关于 T3S 装置对衣原体生物学的更直接贡献知之甚少。尽管 T3S 过程在革兰氏阴性病原体中显示出显着程度的功能保守性，但衣原体定植的高度独特的生态位很可能导致衣原体系统新颖的机制。因此，这些研究将为有关 T3S 机制的知识增加一个新的维度，加深对衣原体介导的疾病的了解，并有可能产生新的预防和治疗疗法。