The iron-infection axis revisited: From mechanistic insights to therapeutic frontiers

Iron is an essential element for both the host and the invading pathogens since its chemically reactive nature makes it favorable for its nutritional value during infection. Pathogens employ high-affinity siderophores to acquire iron. Meanwhile the host sequestrates iron by binding proteins and a suite of regulatory factors including hepcidin, lipocalin-2, and natural resistance-associated macrophage protein 1. These natural immune responses by the host are intimately linked with the inflammatory mechanisms to control infection by restricting access to iron to the pathogen. In the era of increasing antimicrobial resistance, this interplay presents an attractive target for novel drug development, which has led to the clinical use of siderophore-conjugated antimicrobials. This comprehensive overview of the host-pathogen iron interplay, highlighting the dynamics of Iron-infection Axis offers a new paradigm for understanding disease pathogenesis. A deeper appreciation of this axis is expected to accelerate the development of future diagnostic and therapeutic strategies.