Siderophore secretion by Mycobacterium tuberculosis

项目摘要-结核分枝杆菌分泌铁载体 为了抵消宿主体内的铁限制，结核分枝杆菌分泌铁载体，小分子与 高度铁结合的亲和力，称为分枝杆菌毒素(MBT)和羧基分枝杆菌毒素(CMBT)。我们 发现两个小的膜蛋白MmpS4和MmpS5与大的 外排泵MmpL4和MmpL5形成新型内膜组件 不同于所有其他已知细菌铁载体的铁载体分泌系统 分泌系统。该系统也被MTB用于回收铁载体。中断 铁载体通过删除内膜成分回收导致自毒 并完全消除结核分枝杆菌在小鼠体内的复制能力。然而，有几个 铁载体分泌系统的组成尚不清楚。在本提案中，我们将使用 免费的遗传、生化和生物物理方法来鉴定和表征新奇的东西 参与结核分枝杆菌铁载体分泌的蛋白质。

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.