Heme and hemoglobin utilization by Mycobacterium tuberculosis

结核分枝杆菌利用血红素和血红蛋白

• 批准号: 10082420
• 负责人: MICHAEL NIEDERWEIS
• 金额: $ 65.05万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10082420
• 关键词: Affinity; Bacteria; Bacterial Proteins; Binding; Binding Proteins; Biochemical; Biological Assay; Biophysics; Biosensor; Cell surface; Cells; Communicable Diseases; Complex; Cryoelectron Microscopy; Data; Elements; Environment; Gallium; Genetic; Globin; Goals; Granuloma; Growth; Heme; Heme Iron; Hemoglobin; Human; Human body; Infection; Iron; Lipid Bilayers; Membrane; Membrane Proteins; Methods; Molecular; Mus; Mutate; Mycobacterium tuberculosis; Necrosis; Patients; Peptide Hydrolases; Porphyrins; Proteins; Research Project Grants; Role; Siderophores; Source; Structure; System; Tuberculosis; Virulence; X-Ray Crystallography; base; crosslink; experimental study; heme-binding protein; innovation; macrophage; mutant; mycobactins; novel; pathogenic bacteria; small molecule; three dimensional structure; uptake

Project Summary - Heme and hemoglobin utilization by Mycobacterium tuberculosis Mycobacterium tuberculosis (Mtb) is of one of the most important bacterial pathogens. Iron is essential for growth of Mtb, but iron is efficiently sequestered in the human host. Hemoglobin is by far the most prevalent iron source in the human body and is often preferred by bacterial pathogens. Recently, we identified proteins that are essential components of an unprecedented heme and hemoglobin utilization system in Mtb. Interestingly, these novel heme-binding proteins are also required for utilization of hemoglobin indicating that heme is released from hemoglobin at the cell surface of Mtb by an unknown mechanism and then transferred to the heme uptake system. This proposal aims to elucidate the molecular mechanisms of heme and hemoglobin utilization by Mtb. This project will lead to a better understanding of how Mtb gains access to iron during infection. To achieve these goals we employ state-of-the-art genetic, biochemical, biophysical and structural methods.

项目摘要 - 结核分枝杆菌利用血红素和血红蛋白 结核分枝杆菌（Mtb）是最重要的细菌病原体之一。铁是 对于结核分枝杆菌的生长至关重要，但铁可以有效地隔离在人类宿主体内。血红蛋白是 迄今为止，人体内最普遍的铁源，通常是细菌的首选 病原体。最近，我们发现了蛋白质，它们是前所未有的物质的重要组成部分。 结核分枝杆菌中的血红素和血红蛋白利用系统。有趣的是，这些新颖的血红素结合 血红蛋白的利用也需要蛋白质，这表明血红素是从 血红蛋白通过未知机制附着在 Mtb 细胞表面，然后转移到 血红素摄取系统。该提案旨在阐明血红素和血红素的分子机制 结核分枝杆菌对血红蛋白的利用。该项目将帮助人们更好地了解 Mtb 如何获得收益 感染期间获取铁。为了实现这些目标，我们采用最先进的遗传、 生物化学、生物物理和结构方法。