Siderophore secretion by Mycobacterium tuberculosis

项目摘要-结核分枝杆菌的铁载体分泌 为了抵消宿主中的铁限制，结核分枝杆菌分泌铁载体，即具有铁结合能力的小分子。 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 发现两种小的膜蛋白MmpS 4和MmpS 5与大的膜蛋白MmpS 4和MmpS 5相互作用。 外排泵MmpL 4和MmpL 5，以形成一种新的内膜组件。 铁载体分泌系统不同于所有其它已知的细菌铁载体 分泌系统该系统也被Mtb用于回收铁载体。中断 通过删除内膜成分的铁载体再循环导致铁载体自身中毒。 Mtb并完全消除Mtb在小鼠中复制的能力。但几 铁载体分泌系统的组分仍然是未知的。在本提案中，我们将使用 互补的遗传、生物化学和生物物理方法来鉴定和表征新的 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.