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The mycobacterial iron‐dependent regulator IdeR induces ferritin ( bfrB ) by alleviating L sr2 repression
Summary Emerging evidence indicates that precise regulation of iron ( F e) metabolism and maintenance of F e homeostasis in M ycobacterium tuberculosis ( Mtb ) are essential for its survival and proliferation in the host. IdeR is a central transcriptional regulator of Mtb genes involved in F e metab...
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Published in: | Molecular microbiology 2015-12, Vol.98 (5), p.864-877 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Summary
Emerging evidence indicates that precise regulation of iron (
F
e) metabolism and maintenance of
F
e homeostasis in
M
ycobacterium tuberculosis
(
Mtb
) are essential for its survival and proliferation in the host.
IdeR
is a central transcriptional regulator of
Mtb
genes involved in
F
e metabolism. While it is well understood how
IdeR
functions as a repressor, how it induces transcription of a subset of its targets is still unclear. We investigated the molecular mechanism of
IdeR
‐mediated positive regulation of
bfrB
, the gene encoding the major
F
e‐storage protein of
Mtb
. We found that
bfr
B
induction by
F
e required direct interaction of
IdeR
with a
DNA
sequence containing four tandem
IdeR
‐binding boxes located upstream of the
bfr
B
promoter. Results of
in vivo
and
in vitro
transcription assays identified a direct repressor of
bfr
B
, the histone‐like protein
L
sr2.
IdeR
counteracted
L
sr2‐mediated repression
in vitro
, suggesting that
IdeR
induces
bfrB
transcription by antagonizing the repressor activity of
Lsr
2. Together, these results elucidate the main mechanism of
bfrB
positive regulation by
IdeR
and identify
Lsr
2 as a new factor contributing to
F
e homeostasis in mycobacteria. |
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ISSN: | 0950-382X 1365-2958 |
DOI: | 10.1111/mmi.13166 |