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: 8190926
• 负责人: KENNETH A FIELDS
• 金额: $ 22.05万
• 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 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8190926
• 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. PUBLIC HEALTH RELEVANCE: The Chlamydia genus contains species that are important human pathogens. These bacteria have a complex, biphasic developmental cycle and express a type III secretion system essential of development of the anti-host proteins. This proposal contains work designed to explore the link between the developmental cycle and activity of the secretion system.

描述（由申请人提供）：衣原体包含代表美国重大健康问题的成员。由于患病率以及急性和慢性病的健康和社会经济影响，存在着很大的负担。衣原体是强制性的细胞内寄生虫，经历了复杂的发育周期，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展密切相关。另外，衣原体属于外膜的二硫键动力学。在发育周期中具有主导但不完全理解的作用。我们有初步证据表明T3S蛋白参与二硫键粘合的发展相关的变化。我们提出了一种旨在表征T3S设备蛋白之间二硫键的方法的组合，以确定对分泌活性的程度，时间动力学和影响。对分泌效应蛋白的识别和表征已经非常重视，而对于T3S设备对衣原体生物学的更直接贡献的众所周知，相对较少。尽管T3S过程在革兰氏阴性病原体中表现出很大程度的功能保护，但被衣原体殖民的高度独特的利基市场可能导致衣原体系统的新型机制。因此，这些研究将为有关T3S机制的知识增加一个新的维度，从而增强对衣原体介导的疾病的了解，并可能产生新颖的预防和治疗疗法。 公共卫生相关性：衣原体属含有重要的人类病原体。这些细菌具有复杂的双相发育周期，并表达了抗宿主蛋白发育的III型分泌系统。该提案包含旨在探索分泌系统的发展周期和活动之间的联系的工作。