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.

项目总结-结核分枝杆菌分泌铁载体