Fig. 4. A schematic figure depicting carboxymycobactin (cMB) is secreted by M.tb under iron-limited conditions. The MmpL4/5 transporter, in association with the MmpS4 and MmpS5 membrane-associated proteins, is involved in the secretion of the carboxymycobactins. Once carboxymycobactins are secreted, they chelate Fe³⁺ and travel back across the outer membrane and periplasm via the inner membrane importer IrtAB to reach the cytoplasm. Using the FAD-binding domain of IrtA, ferric iron can reduce to ferrous iron in the cytosol and thus dissociate the iron–siderophore complex. The released ferrous irons are used, and excess ferrous irons are stored as ferritins. The binding of irons to the regulator IdeR activates its DNA binding activity, and the expression of several genes is suppressed, which are responsible for siderophores synthesis, secretion, and transport. Simultaneously, iron storage is activated by IdeR-Fe²⁺ binding to the promoters of ferritins (ferritin and bacterioferritin), which prevents iron-mediated toxicity; thus, iron homeostasis is maintained.²⁰⁰.