Iron-regulated protein HupB of Mycobacterium tuberculosis positively regulates siderophore biosynthesis and is essential for growth in macrophages

Mycobacterium tuberculosis expresses the 28-kDa protein HupB (Rv2986c) and the Fe(3+)-specific high-affinity siderophores mycobactin and carboxymycobactin upon iron limitation. The objective of this study was to understand the functional role of HupB in iron acquisition. A hupB mutant strain of M. t...

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Bibliographic Details
Published in:Journal of bacteriology 2014-05, Vol.196 (10), p.1853-1865
Main Authors: Pandey, Satya Deo, Choudhury, Mitali, Yousuf, Suhail, Wheeler, Paul R, Gordon, Stephen V, Ranjan, Akash, Sritharan, Manjula
Format: Article
Language:English
Subjects:
Animals
Bacterial proteins
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bacteriology
Binding sites
Bioassays
Biosynthesis
Cell growth
Cell Line
DNA, Bacterial
Gene Deletion
Gene Expression Regulation, Bacterial - physiology
Gram-positive bacteria
Histones - genetics
Histones - metabolism
Iron
Iron - metabolism
Macrophages, Peritoneal - microbiology
Mice
Mycobacterium tuberculosis
Peptide Synthases - genetics
Peptide Synthases - metabolism
Promoter Regions, Genetic
Protein Binding
Siderophores - biosynthesis
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Summary:Mycobacterium tuberculosis expresses the 28-kDa protein HupB (Rv2986c) and the Fe(3+)-specific high-affinity siderophores mycobactin and carboxymycobactin upon iron limitation. The objective of this study was to understand the functional role of HupB in iron acquisition. A hupB mutant strain of M. tuberculosis, subjected to growth in low-iron medium (0.02 μg Fe ml(-1)), showed a marked reduction of both siderophores with low transcript levels of the mbt genes encoding the MB biosynthetic machinery. Complementation of the mutant strain with hupB restored siderophore production to levels comparable to that of the wild type. We demonstrated the binding of HupB to the mbtB promoter by both electrophoretic mobility shift assays and DNA footprinting. The latter revealed the HupB binding site to be a 10-bp AT-rich region. While negative regulation of the mbt machinery by IdeR is known, this is the first report of positive regulation of the mbt operon by HupB. Interestingly, the mutant strain failed to survive inside macrophages, suggesting that HupB plays an important role in vivo.
ISSN:0021-9193
1098-5530
DOI:10.1128/jb.01483-13