Discovery and characterization of a unique mycobacterial heme acquisition system

Mycobacterium tuberculosis must import iron from its host for survival, and its siderophore-dependent iron acquisition pathways are well established. Here we demonstrate a newly characterized pathway, whereby M. tuberculosis can use free heme and heme from hemoglobin as an iron source. Significantly...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-03, Vol.108 (12), p.5051-5056
Main Authors: Tullius, Michael V, Harmston, Christine A, Owens, Cedric P, Chim, Nicholas, Morse, Robert P, McMath, Lisa M, Iniguez, Angelina, Kimmey, Jacqueline M, Sawaya, Michael R, Whitelegge, Julian P, Horwitz, Marcus A, Goulding, Celia W
Format: Article
Language:English
Subjects:
Bacteria
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Biochemistry
Biological Sciences
Biological Transport - physiology
Carrier proteins
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Membrane - genetics
Cell Membrane - metabolism
Cell walls
Crystal structure
Dimers
Exploration
Genomics
Heme
Heme - genetics
Heme - metabolism
heme iron
Hemoglobin
Hemoglobins
Iron
Iron - metabolism
Membrane proteins
Membranes
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - metabolism
Plasmids
Protein folding
protein secretion
Proteins
Signal transduction
Survival
therapeutics
transmembrane proteins
Tuberculosis
Tuberculosis - drug therapy
Tuberculosis - genetics
Tuberculosis - metabolism
Virulence
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Summary:Mycobacterium tuberculosis must import iron from its host for survival, and its siderophore-dependent iron acquisition pathways are well established. Here we demonstrate a newly characterized pathway, whereby M. tuberculosis can use free heme and heme from hemoglobin as an iron source. Significantly, we identified the genomic region, Rv0202c-Rv0207c, responsible for the passage of heme iron across the mycobacterial membrane. Key players of this heme uptake system were characterized including a secreted protein and two transmembrane proteins, all three specific to mycobacteria. Furthermore, the crystal structure of the key heme carrier protein Rv0203 was found to have a unique fold. The discovery of a unique mycobacterial heme acquisition pathway opens new avenues of exploration into mycobacterial therapeutics.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1009516108