title: Recent developments in understanding the iron acquisition strategies of gram positive pathogens.
abstract: Iron is a versatile redox-active catalyst and a required cofactor within a diverse array of biological processes. To almost all organisms, iron is both essential and potentially toxic, where homeostatic concentrations must be stringently maintained. Within the iron-restricted host, the survival and proliferation of microbial invaders is contingent upon exploiting the host iron pool. Bacteria express a multitude of complex, and often redundant means of acquiring iron, including surface-associated heme-uptake pathways, high affinity iron-scavenging siderophores and transporters of free inorganic iron. Within the last decade, our understanding of iron acquisition by Gram-positive pathogens has expanded substantively, from the discovery of the iron-regulated surface-determinant pathway and numerous unique siderophores through to the detailed elucidation of heme-iron extraction, and heme and siderophore coordination and transfer. This review provides a comprehensive summary of the iron acquisition strategies of notorious Gram-positive pathogens and highlights how both conserved and distinct tactics for acquiring iron contribute to the pathophysiology of these bacteria. Further, a focus on recent structural and mechanistic studies details how these iron acquisition systems may be exploited in the development of novel therapeutics.
authors: Department of Microbiology & Immunology, University of Western Ontario, London, ON N6A 5C1, Canada.
authors: Jessica R
authors: JR
authors: Sheldon
authors: Department of Microbiology & Immunology, University of Western Ontario, London, ON N6A 5C1, Canada deh@uwo.ca.
authors: David E
authors: DE
authors: Heinrichs
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006094:Gram-Positive Bacteria / Q000378:metabolism* / Q000472:pathogenicity; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology*; D007501:Iron / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; D007501:Iron
keywords: ABC transporter; Bacillus anthracis; Corynebacterium diphtheriae; Listeria monocytogenes; Staphylococcus aureus; Streptococcus pneumoniae; heme; inorganic iron; sideromycin; siderophores; substrate-binding protein; vaccine; xenosiderophores