title: Extracellular heme uptake and the challenges of bacterial cell membranes.
abstract: In bacteria, the fine balance of maintaining adequate iron levels while preventing the deleterious effects of excess iron has led to the evolution of sophisticated cellular mechanisms to obtain, store, and regulate iron. Iron uptake provides a significant challenge given its limited bioavailability and need to be transported across the bacterial cell wall and membranes. Pathogenic bacteria have circumvented the iron-availability issue by utilizing the hosts' heme-containing proteins as a source of iron. Once internalized, iron is liberated from the porphyrin enzymatically for cellular processes within the bacterial cell. Heme, a lipophilic and toxic molecule, poses a significant challenge in terms of transport given its chemical reactivity. As such, pathogenic bacteria have evolved sophisticated membrane transporters to coordinate, sequester, and transport heme. Recent advances in the biochemical and structural characterization of the membrane-bound heme transport proteins are discussed in the context of ligand coordination, protein-protein interaction, and heme transfer.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, USA.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Smith
authors.forename: Angela
authors.initials: A
authors.lastname: Wilks
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D008665:Metalloporphyrins / Q000737:chemistry / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D008665:Metalloporphyrins; D011956:Receptors, Cell Surface; C028027:heme receptor; D006418:Heme; D007501:Iron