Discovery and characterization of a unique mycobacterial heme acquisition system
2011
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.
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.
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