Intracellular fungal iron and iron-dependent metabolic processes

Intracellular fungal iron and iron-dependent metabolic processes refer to the complex network of pathways used by fungi to acquire, store, and utilize iron, which is an essential cofactor for numerous cellular functions (Almeida et al., 2013, "The role of iron in fungal virulence"). Iron is critical for fungal virulence and survival, participating in DNA synthesis, the tricarboxylic acid (TCA) cycle, and the mitochondrial electron transport chain (Philpott, 2006, "Iron uptake in fungi"). Because the human host actively sequesters iron to limit pathogen growth—a process known as nutritional immunity—fungi have evolved sophisticated mechanisms such as siderophore secretion and high-affinity iron transporters to scavenge iron (Howard, 1999, "Acquisition, transport, and storage of iron by pathogenic fungi"). Targeting these processes, either through iron chelation or by inhibiting specific iron-dependent enzymes and transporters, represents a potent antifungal strategy (Ibrahim et al., 2007, "Deferasirox for the treatment of mucormycosis"). However, the high conservation of iron-dependent enzymes between fungi and humans poses a significant challenge for achieving selective toxicity, as drugs may inadvertently affect host iron homeostasis (Caza and Kronstad, 2013, "Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens"). Research into fungal-specific iron acquisition pathways, such as the Sit1 transporter or siderophore biosynthesis enzymes, continues to be a promising area for developing narrow-spectrum antifungals with reduced host toxicity (Haas, 2014, "Iron - A key element in fungal pathogenicity").

Other names

Fungal iron metabolismFungal iron homeostasisIron-dependent fungal pathways

Sequestration of essential iron ions and inhibition of iron-dependent enzymatic processes required for fungal growth and virulence.