Iron acquisition strategies in pathogenic fungi

ABSTRACT Iron plays a crucial role in various biological processes, including enzyme function, DNA replication, energy production, oxygen transport, lipid, and carbon metabolism. Although it is abundant in the Earth’s crust, its bioavailability is restricted by the insolubility of ferric iron (Fe³ + ) and the auto-oxidation of ferrous iron (Fe² + ) in oxygen-rich environments. This limitation poses significant challenges for all organisms, including fungi, which have developed intricate mechanisms for iron acquisition and utilization. These mechanisms include reductive iron uptake, siderophore production/transport, and heme utilization. Fungi employ a variety of enzymes—such as ferric reductases, ferroxidases, permeases, and transporters—to regulate intracellular iron levels effectively. The challenge is heightened for pathogenic fungi during infection, as they must compete with the host’s iron-binding proteins like transferrin and lactoferrin, which sequester iron to restrict pathogen growth. This review delves into the iron acquisition strategies of medically important fungi, emphasizing the roles of reductive iron uptake and siderophore pathways. Understanding these mechanisms is vital for enhancing our knowledge of fungal pathogenesis and developing effective treatments. By targeting these iron acquisition processes, new antifungal therapies can be formulated more effectively to combat fungal infections.