Siderophore secretion by Mycobacterium tuberculosis

结核分枝杆菌分泌铁载体

• 批准号: 10379326
• 负责人: MICHAEL NIEDERWEIS
• 金额: $ 19.25万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10379326
• 关键词: Affinity; Binding; Binding Sites; Biochemical; Biological Process; Cells; Chemicals; Core Protein; Environment; Fatty acid glycerol esters; Filtration; Fluorescence Resonance Energy Transfer; Genetic; Growth; Human; Human body; Interruption; Iron; Ligand Binding; Lipids; Mediating; Membrane; Membrane Proteins; Molecular; Multidimensional NMR Techniques; Mus; Mycobacterium tuberculosis; Pathway interactions; Patients; Persons; Phase; Phenotype; Poisoning; Proteins; Recombinants; Recycling; Role; Siderophores; Starvation; Structure; System; Testing; Thin Layer Chromatography; Virulence; acute infection; base; biophysical techniques; efflux pump; experimental study; extracellular; improved; mutant; mycobacterial; mycobactins; novel; periplasm; protein protein interaction; pulmonary granuloma; quantum; small molecule; transposon sequencing; tuberculosis granuloma

Project Summary - Siderophore secretion by Mycobacterium tuberculosis To counteract the iron limitation in the host, Mtb secretes siderophores, small molecules with high iron-binding affinities called mycobactins (MBT) and carboxy-mycobactins (cMBT). We discovered that the two small membrane proteins MmpS4 and MmpS5 interact with the large efflux pumps MmpL4 and MmpL5 to form the inner membrane components of a novel siderophore secretion system that is different from all other known bacterial siderophore secretion systems. This system is also used by Mtb to recycle siderophores. Interruption of siderophore recycling by deleting the inner membrane components leads to self-poisoning of Mtb and completely eliminates the ability of Mtb to replicate in mice. However, several components of the siderophore secretion system are still unknown. In this proposal we will use complimentary genetic, biochemical and biophysical methods to identify and characterize novel proteins involved in siderophore secretion by Mtb.

项目摘要 - 结核分枝杆菌分泌铁载体 为了抵消宿主体内铁的限制，结核分枝杆菌会分泌铁载体，这是一种小分子，具有 高铁结合亲和力称为分枝杆菌素 (MBT) 和羧基分枝杆菌素 (cMBT)。我们 发现两个小膜蛋白 MmpS4 和 MmpS5 与大膜蛋白相互作用 外排泵 MmpL4 和 MmpL5 形成新型的内膜组件 与所有其他已知细菌铁载体不同的铁载体分泌系统 分泌系统。 Mtb 也使用该系统来回收铁载体。中断 通过删除内膜成分来回收铁载体会导致铁载体的自中毒 消除 Mtb 并完全消除 Mtb 在小鼠体内复制的能力。然而，几个 铁载体分泌系统的组成部分仍然未知。在这个提案中我们将使用 互补的遗传、生物化学和生物物理方法来识别和表征新的 参与 Mtb 铁载体分泌的蛋白质。