To multiply and cause disease in the host, Mycobacterium tuberculosis must acquire
iron from the extracellular environment at sites of replication. To do so, the bacterium releases high-affinity
iron-binding
siderophores called
exochelins. In previous studies, we have described the purification and characterization of the exochelin family of molecules. These molecules share a common core structure with another type of high-affinity
iron-binding molecule located in the cell wall of M.
tuberculosis: the
mycobactins. The water-soluble
exochelins differ from each other and from water insoluble
mycobactins in polarity, which is dependent primarily upon the length and modifications of an alkyl side chain. In this study, we have investigated the capacity of purified
exochelins to remove
iron from host high-affinity
iron-binding molecules, and to transfer
iron to
mycobactins. Purified desferri-
exochelins rapidly removed
iron from human
transferrin, whether it was 95 or 40%
iron saturated, its approximate percent saturation in human serum, and from human
lactoferrin. Desferri-
exochelins also removed
iron, but at a slower rate, from the
iron storage
protein ferritin. Purified ferri-
exochelins, but not
iron transferrin, transferred
iron to desferri-
mycobactins in the cell wall of live bacteria. To explore the possibility that the transfer
iron from
exochelins to
mycobactins was influenced by their polarity, we investigated the influence of polarity on the
iron affinity of
exochelins.
Exochelins of different polarity exchanged
iron equally with each other. This study supports the concept that
exochelins acquire
iron for M.
tuberculosis by removing this
element from host
iron-binding proteins and transferring it to desferri-
mycobactins in the cell wall of the bacterium. The finding that ferri-
exochelins but not
iron transferrin transfer
iron to
mycobactins in the cell wall underscores the importance of
exochelins in
iron acquisition. This study also shows that the variable alkyl side chain on the core structure of
exochelins and
mycobactins, the principal determinant of their polarity, has little or no influence on their
iron affinity.