The Mycobacterium tuberculosis High-Affinity Iron Importer, IrtA, Contains an FAD-Binding Domain

Ironis an essential nutrientnot freely available to microorganisms infecting mammals. To overcome irondeficiency, bacteria have evolved various strategies including the synthesis and secretion of high-affinity iron chelatorsknown as siderophores. The siderophoresproduced and secreted by Mycobacterium tuberculosis, exomycobactins, compete for ironwith host iron-binding proteinsand, together with the iron-regulated ABC transporter IrtAB, are required for the survival of M. tuberculosis in irondeficient conditions and for normal replication in macrophages and in mice. This study further characterizes the role of IrtAB in M. tuberculosis ironacquisition. Our results demonstrate a role for IrtAB in ironimport and show that the amino terminus domain of IrtA is a flavin-adenine dinucleotide-binding domain essential for ironacquisition. These results suggest a model in which the amino terminus of IrtA functions to couple irontransport and assimilation. ′