Ironed Out: A Bacterial Siderophore Primer

Abstract

Nearly all living organisms require iron, the fourth most abundant element in the earth's crust, for survival. However, despite its abundance, ferric ion has extremely low solubility in aerobic environments at physiological pH (10 −18 M), and the Fe II /Fe III redox couple leads the production of destructive oxygen radicals via Fenton chemistry. To solubilize and regulate iron in biological systems, many organisms rely on proteins and small molecules to chelate iron and make it bioavailable. This tedious management of the distribution of iron has led to an arms race between mammals and microorganisms, each with the purpose to ensure their own supply of iron at the expense of the other. In order to acquire iron, microorganisms such as bacteria and fungi have developed small‐molecule chelators called siderophores that bind environmental iron and are actively reincorporated into the cell via specific receptors. When a bacterial pathogen invades a mammalian host, its ability to steal iron from the host's iron stores is determinant in the success of its pathogenicity. This article seeks to provide a high‐level perspective on the structural variety and coordination properties of siderophores, as well as on the biological relevance of siderophore‐mediated iron acquisition for bacterial survival. The promise of using or altering these iron acquisition pathways for medicinal and theranostic applications is also discussed.