Mycobacterium tuberculosis infects one-third of humanity and is one of the world's most important infectious agents from the standpoint of morbidity and mortality. Its capacity to infect the host is closely linked to its ability to acquire iron. Free iron is very limited in the host, particularly in extracellular sites, owing to the high affinity with which it is held by host iron-binding proteins. Mycobacteria produce small water-soluble siderophores called exochelins. It is proposed that exochelins bind iron in the extracellular aqueous environment and transport the metal to another high affinity iron-binding molecule in the cell envelope of the mycobacteria called mycobactin. We described the structural characterization of exochelins from M. tuberculosis by mass spectrometry in a 1995 PNAS paper and am now working on the NMR structures of the desferriand metal-bound exochelins and will use MidasPlus to visualize the structures. Knowledge of the composition and structure of exochelins may point to new strategies for interfering with their iron-acquiring function and, therefore, the growth of M. tuberculosis in the host. This in turn may provide a rational basis for the design of new drugs to combat tuberculosis.
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