Identification of an ABC Transporter Required for Iron Acquisition and Virulence inMycobacterium tuberculosis

Iron availability affects the course of tuberculosis infection, and the ability to acquire this metal is known to be essential for replication ofMycobacterium tuberculosis in human macrophages.M. tuberculosis overcomes iron deficiency by producing siderophores. The relevance of siderophore synthesis for iron acquisition byM. tuberculosis has been demonstrated, but the molecules involved in iron uptake are currently unknown. We have identified two genes (irtA andirtB ) encoding an ABC transporter similar to the YbtPQ system involved in iron transport inYersinia pestis . Inactivation of theirtAB system decreases the ability ofM. tuberculosis to survive iron-deficient conditions. IrtA and -B do not participate in siderophore synthesis or secretion but are required for efficient utilization of iron from Fe-carboxymycobactin, as well as replication ofM. tuberculosis in human macrophages and in mouse lungs. We postulate that IrtAB is a transporter of Fe-carboxymycobactin. TheirtAB genes are located in a chromosomal region previously shown to contain genes regulated by iron and the major iron regulator IdeR. Taken together, our results and previous observations made by other groups regarding two other genes in this region indicate that this gene cluster is dedicated to siderophore synthesis and transport inM. tuberculosis.