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Further Characterization of a Unique Mycobacterial Heme Uptake System
Author(s) -
Goulding Celia Whitford,
Owens Cedric,
Chim Nick,
Harmston Christine,
Iniguez Angelina,
Contreras Heidi,
Morse Robert
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.801.1
Subject(s) - heme , biochemistry , mycobacterium tuberculosis , hemeprotein , atp binding cassette transporter , chemistry , transmembrane protein , transporter , biology , gene , tuberculosis , enzyme , receptor , medicine , pathology
Mycobacterium tuberculosis (Mtb), the primary agent of tuberculosis, is one of the most frequent causes of death by a single infectious agent. Mtb must import iron from its host for survival, and its siderophore‐dependent iron acquisition pathways are well established. Recently, we documented a newly characterized pathway, whereby Mtb can use free heme and heme from hemoglobin as an iron source. Significantly, we identified the genomic region responsible for the passage of heme‐iron across the mycobacterial membrane. For the first time, key players of this heme uptake system were biochemically characterized including a secreted heme‐binding protein and two transmembrane proteins (MmpL3 ad MmpL11), all three specific to mycobacteria. Furthermore, within the Mtb cytosol, we have characterized a heme‐degrading protein MhuD, which releases iron from the heme tetrapyrrole ring for utilization by Mtb. We have extended our studies and will discuss further characterization of genes involved in this heme acquisition pathway, biochemical analysis of heme transfer from the secreted heme carrier protein to soluble domains of the putative heme transporters, as well as confirmation that the Mb essential gene which encodes for MmpL3, plays a role in mycobacterial heme transport. The discovery of this unique mycobacterial heme acquisition pathway opens new avenues of exploration into mycobacterial therapeutics. Sources of research funding are NIH NIAID/NIGMS and the American Lung Association.