Siderophore secretion by Mycobacterium tuberculosis

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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.