Mechanisms and regulation of iron and heme utilization in Gram-negative bacteria

Iron and heme are essential nutrients for most pathogenic microorganisms and play a pivotal role in microbial pathogenesis. To survive within the iron-limited environment of the host, bacteria utilize iron-siderophore complexes, iron-binding proteins (transferrin, lactoferrin), free heme and heme bound to hemoproteins (hemoglobin, haptoglobin, hemopexin). A mechanism of iron and heme transport depends on the structures of Gram-negative bacterial membranes. Siderophores, hemophores and outer membrane receptors take part in iron or heme binding. The transport of these ligands across the outer membrane involves outer membrane receptors. The energy for this transport is delivered from the inner membrane by a TonB-ExbB-ExbD complex. The transport across the cytoplasmic membrane involves periplasmic and inner membrane proteins comprising the ABC systems, which utilize the energy derived from ATP hydrolysis. The major regulatory role in iron homeostasis plays a Fur-Fe2+ repressor.