How bacteria capture iron from heme

Heme Heme is ubiquitous, abundant, and vitally necessary as a cofactor in oxidoreduction and gas transport. Most microorganisms display a complete heme biosynthetic pathway, but are able to acquire the essential ferrous iron from exogenous heme. Free heme or heme arising from hemoproteins is internalized intact and subsequently degraded in the cytosol. Diverse mechanisms for heme uptake have been identified in bacteria. They involve extracellular hemoproteins (hemophores) that capture heme and deliver it to bacteria and cell surface receptors that bind heme, hemoproteins, and/or hemophores. Surface receptors of Gram-positive bacteria are cell-wall anchored proteins that scavenge heme and relay it to specific ABC transporters involved in heme internalization. The absence of these newly identified mechanisms from higher eukaryotic organisms makes them potential targets for new antibacterial drugs, especially since there is growing evidence that heme utilization systems are required for bacterial virulence.
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Bacteria capture iron from heme by keeping tetrapyrrol skeleton intact. PNAS USA June 29, 2009, doi 10.1073/pnas.0903842106
Because heme is a major iron-containing molecule in vertebrates, the ability to use heme-bound iron is a determining factor in successful infection by bacterial pathogens. Until today, all known enzymes performing iron extraction from heme did so through the rupture of the tetrapyrrol skeleton. Here, we identified 2 Escherichia coli paralogs, YfeX and EfeB, without any previously known physiological functions. YfeX and EfeB promote iron extraction from heme preserving the tetrapyrrol ring intact. This novel enzymatic reaction corresponds to the deferrochelation of the heme. YfeX and EfeB are the sole proteins able to provide iron from exogenous heme sources to E. coli. YfeX is located in the cytoplasm. EfeB is periplasmic and enables iron extraction from heme in the periplasm and iron uptake in the absence of any heme permease. YfeX and EfeB are widespread and highly conserved in bacteria. We propose that their physiological function is to retrieve iron from heme.