Iron and siderophores in fungal–host interactions

Most fungi and bacteria express specific mechanisms for the acquisition of iron from the hosts they infect for their own survival. This is primarily because iron plays a key catalytic role in various vital cellular reactions in conjunction with the fact that iron is not freely available in these environments due to host sequestration. High-affinity iron uptake systems, such as siderophore-mediated iron uptake and reductive iron assimilation, enable fungi to acquire limited iron from animal or plant hosts. Regulating iron uptake is crucial to maintain iron homeostasis, a state necessary to avoid iron-induced toxicity from iron abundance, while simultaneously supplying iron required for biochemical demand. Siderophores play diverse roles in fungal–host interactions, many of which have been principally delineated from gene deletions in non-ribosomal peptide synthetases, enzymes required for siderophore biosynthesis. These analyses have demonstrated that siderophores are required for virulence, resistance to oxidative stress, asexual/sexual development, iron storage, and protection against iron-induced toxicity in some fungal organisms. In this review, the strategies fungi employ to obtain iron, siderophore biosynthesis, and the regulatory mechanisms governing iron homeostasis will be discussed with an emphasis on siderophore function and relevance for fungal organisms in their interactions with their hosts.