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

The Mycobacterium tuberculosis High-Affinity Iron Importer, IrtA, Contains an FAD-Binding Domain ▿ † Michelle B. Ryndak 1 , Shuishu Wang 3 , Issar Smith 1 , 2 , and G. Marcela Rodriguez 1 , 2 , * 1 Public Health Research Institute Center 2 Department of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 225 Warren Street, Newark, New Jersey 07103 3 Department of Biochemistry, Uniformed Services University of Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814 ABSTRACT Iron is an essential nutrient not freely available to microorganisms infecting mammals. To overcome iron deficiency, bacteria have evolved various strategies including the synthesis and secretion of high-affinity iron chelators known as siderophores. The siderophores produced and secreted by Mycobacterium tuberculosis , exomycobactins, compete for iron with host iron-binding proteins and, together with the iron-regulated ABC transporter IrtAB, are required for the survival of M. tuberculosis in iron deficient conditions and for normal replication in macrophages and in mice. This study further characterizes the role of IrtAB in M. tuberculosis iron acquisition. Our results demonstrate a role for IrtAB in iron import and show that the amino terminus domain of IrtA is a flavin-adenine dinucleotide-binding domain essential for iron acquisition. These results suggest a model in which the amino terminus of IrtA functions to couple iron transport and assimilation. ′