Iron Uptake in Mycobacteria

Abstract

This chapter highlights both the well established and the yet poorly understood aspects of siderophoremediated iron acquisition in pathogenic and nonpathogenic mycobacteria, with a particular emphasis in the siderophore system of Mycobacterium tuberculosis. The M. tuberculosis siderophore system is believed to play a crucial role in the procurement of a suitable iron supply to support bacterial multiplication in vivo and to be a key factor in the ability of this human pathogen to produce successful infections. The mycobacteria examined for iron-acquisition systems appear to rely on siderophores with high affinity for the ferric ion as the primary mechanism for iron acquisition. Transcription of genes of the exochelin (EXC) and mycobactin/carboxymycobactin (MBT/CMBT) systems is derepressed when the bacterium experiences iron limitations, thus leading to siderophore biosynthesis and siderophore-mediated iron uptake. Several Mycobacterium species produce two structurally related families of high-affinity Fe3+-binding siderophores, the MBTs and the CMBTs. Mutational analysis has conclusively linked the mbt gene cluster to production of both MBTs and CMBTs. Mutational analysis has conclusively linked the mbt gene cluster to production of both MBTs and CMBTs. Several Mycobacterium species that are normally found as environmental saprophytes release EXCs, the nonribosomally synthesized pentapeptidebased or hexapeptide-based siderophores, into the extracellular environment. More recently, analogues of salicyl-AMS have also been demonstrated to block MBT/CMBT biosynthesis and M. tuberculosis multiplication in iron-limiting conditions.