Characterizing the Redoxome of Chlamydia and Its Host Cell

衣原体及其宿主细胞氧化还原体的表征

• 批准号: 10723036
• 负责人: Scot P Ouellette
• 金额: $ 24.19万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-17 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723036
• 关键词: Address; Adult; Affect; Asthma; Bacteria; Bacterial Proteins; Biology; Blindness; Cell Culture Techniques; Cells; Centers for Disease Control and Prevention (U.S.); Characteristics; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Chronic; Complex; Complication; Dependence; Developed Countries; Developing Countries; Development; Disease; Equilibrium; Follow-Up Studies; Funding; Gene Expression Profile; Genes; Genetic; Genetic Techniques; Genome; Goals; Growth; Growth and Development function; Healthcare Systems; Heart Diseases; Human; In Vitro; Incidence; Infection; Infertility; Link; Maps; Mass Spectrum Analysis; Mediator; Metabolic; Morbidity - disease rate; Morphology; Mutate; NADP; Organism; Oxidation-Reduction; Pathogenesis; Pathway interactions; Patients; Pelvic Inflammatory Disease; Pneumonia; Proteins; Reducing Agents; Regulation; Reiter Disease; Reporting; Respiratory Tract Infections; Sexually Transmitted Diseases; Side; Signal Transduction; Symptoms; System; TXN gene; Techniques; Therapeutic Agents; Time; Trachoma; Work; candidate identification; candidate selection; design; disulfide bond; environmental change; experimental study; human pathogen; in vivo; infection burden; mutant; normal microbiota; novel therapeutics; oxidation; pathogen; pathogenic bacteria; prevent; stem; thioredoxin reductase; tool; tubal infertility

Project Summary: Characterizing the Redoxome of Chlamydia and Its Host Cell 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 also alternates 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 established mass spectrometry-based approaches to evaluate proteins subjected to redox regulation in both the host and bacterium. The hypothesis of the proposed work is that Chlamydia uses redox signaling to trigger secondary differentiation from the replicative to the infectious form of the organism. The major goals of this two-year funding proposal are to identify host and bacterial proteins subjected to redox regulation as a first step towards addressing our hypothesis. Selected wild-type and mutant proteins will be evaluated for changes in their redox status both in vitro and in cell culture. Results from this study will advance our understanding of this important pathogen and lead to further work to characterize the function of identified redox-regulated proteins. This may, in turn, lead to the design of novel therapeutic agents that are specific for Chlamydia. This will allow for minimal effects on normal flora for patients receiving treatment for this highly prevalent disease.

项目摘要：衣原体及其宿主细胞的氧化还原体表征 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会在不同的功能和形态形式之间交替，也被提及 作为其发展周期。这些观察结果，结合其专性细胞内依赖性，使得 衣原体是一种很难对付的微生物.然而，最近发展的遗传工具， 衣原体感染的机制大大增强了我们对这种病原体的了解。这项建议 应用这些新的遗传技术和基于质谱的 评估宿主和细菌中受氧化还原调节的蛋白质的方法。的假设 这项工作的一个重要方面是，衣原体利用氧化还原信号来触发从大肠杆菌到大肠杆菌的次级分化。 复制到生物体的传染形式。这项为期两年的拨款建议的主要目标是 鉴定宿主和细菌蛋白质进行氧化还原调节作为第一步，以解决我们的 假说.将评估选定的野生型和突变体蛋白质的氧化还原状态的变化， 体外和细胞培养中。这项研究的结果将促进我们对这种重要病原体的了解， 导致进一步的工作，以确定氧化还原调节蛋白的功能。这可能反过来导致 设计新的衣原体特异性治疗药物。这将允许对 正常的植物群对于接受治疗这种高度流行的疾病的患者。