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.

结核分枝杆菌对血红素和血红蛋白的利用 结核分枝杆菌（Mycobacterium tuberculosis，Mtb）是最重要的致病菌之一。铁是 铁是结核分枝杆菌生长所必需的，但铁在人类宿主中被有效地隔离。血红蛋白是 到目前为止，铁是人体中最普遍的铁源， 病原体最近，我们发现了一些蛋白质，它们是一种前所未有的 结核分枝杆菌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 血红蛋白通过一种未知的机制在结核分枝杆菌的细胞表面，然后转移到 血红素摄取系统该建议旨在阐明血红素和 结核分枝杆菌血红蛋白利用率该项目将导致更好地了解结核病如何获得 在感染期间获得铁。为了实现这些目标，我们采用了最先进的基因， 生物化学、生物物理和结构方法。