Identification of an ABC transporter required for iron acquisition and virulence in Mycobacterium tuberculosis

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

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-carboxymycebactin, as well as replication of M. tuberculosis in human macrophages and in mouse lungs. We postulate thai 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.

Original languageEnglish (US)
Pages (from-to)424-430
Number of pages7
JournalJournal of bacteriology
Volume188
Issue number2
DOIs
StatePublished - Jan 1 2006

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ATP-Binding Cassette Transporters
Mycobacterium tuberculosis
Virulence
Iron
Siderophores
Genes
Macrophages
Yersinia pestis
Multigene Family
Tuberculosis
Metals
Lung

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

Cite this

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abstract = "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-carboxymycebactin, as well as replication of M. tuberculosis in human macrophages and in mouse lungs. We postulate thai 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.",
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Identification of an ABC transporter required for iron acquisition and virulence in Mycobacterium tuberculosis. / Rodriguez, G. Marcela; Smith, Issar.

In: Journal of bacteriology, Vol. 188, No. 2, 01.01.2006, p. 424-430.

Research output: Contribution to journalArticle

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