Metabolic Control of Brucellosis

布鲁氏菌病的代谢控制

• 批准号: 9978361
• 负责人: Jerod Skyberg
• 金额: $ 22.62万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-10 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978361
• 关键词: Aconitic Acid; Affect; Alveolar Macrophages; Annual Reports; Anti-Bacterial Agents; Antibiotic Therapy; Antimicrobial Effect; Attenuated; Bacteria; Bone Marrow; Brucella; Brucella melitensis; Brucellosis; Carbon; Cells; Chimera organism; Chronic; Consumption; Data; Disease; Fatty Acids; Flow Cytometry; Future; Genes; Glucose; Glucose Transporter; Glycolysis; Goals; Growth; Health; Human; Immune response; Infection; Infection Control; Interferon Type II; Isocitrate Lyase; Knowledge; Liver; Lung; Mass Fragmentography; Mediating; Metabolic; Metabolic Control; Metabolism; Mus; Organ; Oxides; Pathogenesis; Production; Role; Shunt Device; Signal Transduction; Sorting - Cell Movement; Source; Spleen; Symptoms; Testing; Therapeutic; Time; Tissues; Toll-like receptors; Vaccines; Virulence; Work; Zoonoses; body system; cell type; chronic infection; cytokine; design; glyoxylate; improved; in vivo; interest; interstitial; macrophage; mutant; neglect; prevent; protective effect; relapse risk

Abstract: Brucella spp can infect almost any organ or organ system in humans and thus Brucella must adapt to different metabolic conditions encountered in these tissues. However, the local availability of carbon sources possibly used by Brucella is unclear, if not controversial. Therefore, determining the metabolic conditions within target organs of Brucella, and how these conditions are affected by the host immune response, is essential to understand how Brucella is able to cause multifocal disease. Here we show MyD88 signaling regulates host metabolism, which in turn alters the metabolic requirements for Brucella virulence. In the proposed studies, we will investigate the temporal, and tissue-specific role of MyD88 on host metabolism during brucellosis and determine the effects of MyD88-dependent metabolites on control of infection.

摘要： 布鲁氏菌几乎可以感染人类的任何器官或器官系统， 必须适应这些组织中遇到的不同代谢条件。但当地 布鲁氏菌可能使用的碳源的可用性如果不是有争议的话，也是不清楚的。因此，我们认为， 确定布鲁氏菌靶器官内的代谢条件，以及这些条件 受宿主免疫反应的影响，对于了解布鲁氏菌如何能够 导致多灶性疾病。在这里，我们展示了MyD88信号调节宿主代谢， 反过来改变了布鲁氏菌毒力的代谢要求。在建议的研究中，我们会 研究MyD88在布鲁氏菌病期间对宿主代谢的时间和组织特异性作用 并确定MyD88依赖性代谢物对感染控制的作用。