Iron acquisition, assimilation and regulation in mycobacteria

Iron is as crucial to the pathogen as it is to the host. The tuberculosis causing bacillus, Mycobacterium tuberculosis (M.tb), is an exceptionally efficient pathogen that has evolved proficient mechanisms to sequester iron from the host despite its thick mycolate-rich outer covering and a highly impermeable membrane of phagolysosome within which it persists inside an infected host macrophage. Further, both overindulgence and moderation of iron inside a host are a threat to mycobacterial persistence. While for removing iron from the host reservoirs, mycobacteria synthesize molecules that have several times higher affinity for iron than their host counterparts, they also synthesize molecules for efficient storage of excess iron. This is supported by tightly regulated iron dependent global gene expressions. In this review we discuss the various molecules and pathways evolved by mycobacteria for an efficient iron metabolism. We also discuss the less investigated players, like iron responsive proteins and iron responsive elements in mycobacteria, and highlight the lacunae in our current understanding of iron acquisition and utilization in mycobacteria with an ultimate aim to make iron metabolism as a possible anti-mycobacterial target.

► Iron-withholding’ is vital for the host defense against mycobacterial pathogenesis.
► Iron is critical for intracellular survival of pathogenic mycobacteria.
► We discuss methods of iron acquisition, assimilation and regulation in mycobacteria.
► Lacunae in the present concepts of iron acquisition in mycobacteria are conveyed.
► We also discuss iron metabolism as a possible anti-mycobacterial target.