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：描述衣原体及其宿主细胞的氧化还原 衣原体是一种义务的细胞内细菌病原体，会导致一系列严重疾病 人类。在发达国家，沙眼衣原体是细菌性传播的主要原因 感染（STI）。确实，疾病控制中心的最新报告突出了发病率的增加 STI，衣原体感染始终超过所有其他类型。在发展中国家，C。 气管瘤不仅是STI的重要原因，而且还导致了传染性的主要原因 可预防的失明，沙眼。衣原体感染的主要关注点是它们经常是 无症状和未诊断，可能导致慢性后遗症。这些包括骨盆炎症 疾病，输卵管因子不育症和气管梭菌的反应性关节炎。因此，衣原体疾病 在世界各地的医疗保健系统上仍然承担重大负担。 为了适应义务细胞内生长，衣原体大大降低了其基因组大小和 从各种途径中消除了基因，因为它依靠宿主细胞来代谢需求。这种病原体 在正常生长期间，不同功能和形态形式之间也交替，也称为 作为其发育周期。这些观察结果，结合了其专有的细胞内依赖，使得 衣原体是一种艰难的生物。但是，最近开发了研究的遗传工具 衣原体从机械上显着增强了我们对这种病原体的理解。这个建议 应用这些新的遗传技术和建立的质谱法的组合 评估受宿主和细菌氧化还原调节的蛋白质的方法。假设 拟议的工作是，衣原体使用氧化还原信号传导触发了与 复制有机体的传染性形式。这项为期两年的资助建议的主要目标是 确定受氧化还原调节的宿主和细菌蛋白作为解决我们的第一步 假设。将评估选定的野生型和突变蛋白的氧化还原状态的变化 体外和细胞培养。这项研究的结果将促进我们对这一重要病原体和 导致进一步的工作以表征已鉴定的氧化还原调节蛋白的功能。反过来，这可能是领导 针对特定于衣原体的新型治疗剂的设计。这将使对 接受这种高度普遍疾病治疗的患者的正常菌群。