Affiliation:
1. TB Center, The Public Health Research Institute at the International Center for Public Health, 225 Warren St., Newark, New Jersey 07103
Abstract
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-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.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
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