Fungal iron and manganese pools

The concept of fungal iron and manganese pools refers to the intracellular reservoirs of these essential transition metals that fungi maintain to support the activity of numerous iron-dependent and manganese-dependent enzymes. In pathogenic fungi like Candida albicans and Aspergillus fumigatus, these pools are dynamically regulated to ensure survival under metal-limiting conditions imposed by the host's nutritional immunity. Research indicates that antifungal treatments, such as fluconazole, trigger a significant remodeling of these metal networks, causing the fungus to mobilize stored iron and manganese to maintain the function of critical enzymes like catalases, peroxidases, and those involved in the ergosterol biosynthetic pathway. While not a single therapeutic target, the transporters and regulatory proteins governing these pools, such as Ccc1 and HapX, are considered potential targets for novel antifungal strategies. Understanding the interplay between these metal pools is crucial for developing therapies that disrupt fungal adaptation to drug stress and host environments.

Other names

Fungal iron and aluminum poolsLabile iron poolVacuolar iron storageManganese-dependent iron homeostasis

Fluconazole disrupts ergosterol biosynthesis, leading to the remodeling of metal homeostasis and mobilization of iron and manganese pools to support essential enzymes. Iron chelators like deferiprone sequester iron, limiting its availability for fungal growth.