Discovery and characterization of a unique mycobacterial heme acquisition system
- 7 March 2011
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (12), 5051-5056
- https://doi.org/10.1073/pnas.1009516108
Abstract
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.Keywords
This publication has 45 references indexed in Scilit:
- Unusual Diheme Conformation of the Heme-Degrading Protein from Mycobacterium tuberculosisJournal of Molecular Biology, 2010
- Unique Structure and Stability of HmuY, a Novel Heme-Binding Protein of Porphyromonas gingivalisPLoS Pathogens, 2009
- Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivoProceedings of the National Academy of Sciences of the United States of America, 2009
- A Replication-Limited Recombinant Mycobacterium bovis BCG Vaccine against Tuberculosis Designed for Human Immunodeficiency Virus-Positive Persons Is Safer and More Efficacious than BCGInfection and Immunity, 2008
- Searching protein structure databases with DaliLite v.3Bioinformatics, 2008
- Bacillus anthracis Secretes Proteins That Mediate Heme Acquisition from HemoglobinPLoS Pathogens, 2008
- The metabolic activity of Mycobacterium tuberculosis, assessed by use of a novel inducible GFP expression system, correlates with its capacity to inhibit phagosomal maturation and acidification in human macrophagesMolecular Microbiology, 2008
- Heme acquisition by hemophoresBioMetals, 2007
- Interaction between Polyketide Synthase and Transporter Suggests Coupled Synthesis and Export of Virulence Lipid in M. tuberculosisPLoS Pathogens, 2005
- Inference of Protein Function from Protein StructureStructure, 2005