Iron uptake and intracellular metal transfer in mycobacteria mediated by xenosiderophores

Growth promotion was tested using M. smegmatis wild type strain, an exochelin-deficient mutant, and M. fortuitum employing a broad variety of xenosiderophores including hydroxamates, catecholates and α-hydroxy carboxylic acids. The experiments revealed that utilization of siderophore-bound iron is substrate specific suggesting high-affinity siderophore receptor and transport systems. Concentration-dependent uptake of a selected xenosiderophore (fericrocin) in M. smegmatis showed saturation kinetics and uptake was inhibited by respiratory poisons. In situ Mossbauer spectroscopy of ferricrocin uptake in M. smegmatis indicated rapid intracellular reductive removal of the metal excluding intracellular ferricrocin accumulation. The ultimate intracellular iron pool is represented by a compound (δ = 0.43 mm s^-1, ΔE(Q) = 1.03 mm s^-1) which has also been found in many other microorganisms and does not represent a bacterioferritin, cytochrome or iron-sulfur cluster. By contrast, iron uptake via citrate - a compound exhibiting a very low complex stability constant - involves ligand exchange with mycobactin. Mycobactin has merely a transient role. The ultimate storage compound is an E.coli-type bacterioferritin, in which over 90% of cellular iron is located.