War-Fe-re: iron at the core of fungal virulence and host immunity

Abstract

Iron acquisition is a bona fide virulence determinant. The successful colonization of the mammalian host requires that microorganisms overcome the Fe aridity of this milieu in which the levels of circulating Fe are maintained exceedingly low both through the compartmentalization of this nutrient within cells as well as the tight binding of Fe to host circulating proteins and ligands. Microbes notoriously employ multiple strategies for high affinity Fe acquisition from the host that rely either on the expression of receptors for host Fe-binding proteins and ligands, its reduction by cell surface reductases or the utilization of siderophores, small organic molecules with very high affinity for Fe(3+). This review will discuss the multiple mechanisms deployed by fungal pathogens in Fe acquisition focusing on the role of siderophore utilization in virulence as well as host immune strategies of iron withholding and emerging clinical evidence that human disorders of Fe homeostasis can act as modifiers of infectious disease.