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.

Keywords: ABC transporter; Bacillus anthracis; Corynebacterium diphtheriae; Listeria monocytogenes; Staphylococcus aureus; Streptococcus pneumoniae; heme; inorganic iron; sideromycin; siderophores; substrate-binding protein; vaccine; xenosiderophores.