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Journal of Bacteriology, January 2006, p. 424-430, Vol. 188, No. 2
0021-9193/06/$08.00+0     doi:10.1128/JB.188.2.424-430.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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

G. Marcela Rodriguez* and Issar Smith

TB Center, The Public Health Research Institute at the International Center for Public Health, 225 Warren St., Newark, New Jersey 07103

Received 5 August 2005/ Accepted 20 October 2005

Iron availability affects the course of tuberculosis infection, and the ability to acquire this metal is known to be essential for replication of Mycobacterium tuberculosis in human macrophages. M. tuberculosis overcomes iron deficiency by producing siderophores. The relevance of siderophore synthesis for iron acquisition by M. tuberculosis has been demonstrated, but the molecules involved in iron uptake are currently unknown. We have identified two genes (irtA and irtB) encoding an ABC transporter similar to the YbtPQ system involved in iron transport in Yersinia pestis. Inactivation of the irtAB system decreases the ability of M. 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 of M. tuberculosis in human macrophages and in mouse lungs. We postulate that IrtAB is a transporter of Fe-carboxymycobactin. The irtAB 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 in M. tuberculosis.

* Corresponding author. Mailing address: TB Center, The Public Health Research Institute at the International Center for Public Health, 225 Warren St., Newark, NJ 07103. Phone: (973) 854-3262. Fax: (973) 854-3101. E-mail: marcela{at}phir.org.

Journal of Bacteriology, January 2006, p. 424-430, Vol. 188, No. 2
0021-9193/06/$08.00+0     doi:10.1128/JB.188.2.424-430.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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