Abstract
Iron is an essential nutrient for virtually all organisms and acts as a cofactor for many key enzymes of major metabolic pathways. Furthermore, iron plays a critical role in pathogen-host interactions. In this study, we analyzed metabolomic changes associated with iron availability and the iron regulatory protein Cir1 in a human fungal pathogen Cryptococcus neoformans. Our metabolite analysis revealed that Cir1 influences the glycolytic pathway, ergosterol biosynthesis and inositol metabolism, which require numerous iron-dependent enzymes and play important roles in pathogenesis and antifungal sensitivity of the fungus. Moreover, we demonstrated that increased cellular iron content and altered gene expression in the cir1 mutant contributed to metabolite changes. Our study provides a new insight into iron regulation and the role of Cir1 in metabolome of C. neoformans.
Highlights
Iron is an essential nutrient for virtually all organisms and plays as a cofactor for many key enzymes of major metabolic pathways, such as the tricarboxylic acid cycle, respiration, amino acid biosynthesis, and the synthesis of lipids and sterols [1]
We aimed to identify specific metabolic pathway that is mostly influenced by iron or Cir1 and to understand the role of Cir1 in the metabolome of C. neoformans
The current study focused on determining the influence of Cir1 on the metabolome in C. neoformans
Summary
Iron is an essential nutrient for virtually all organisms and plays as a cofactor for many key enzymes of major metabolic pathways, such as the tricarboxylic acid cycle, respiration, amino acid biosynthesis, and the synthesis of lipids and sterols [1]. Acquisition of iron from the environment is problematic, mainly because of its insoluble nature under aerobic conditions. To overcome extremely low bioavailability of iron, organisms have developed various efficient iron transport systems. Examples include reduction of ferric iron to ferrous iron to increase its permeability and secretion of iron chelating molecules siderophores [2]. Free iron catalyzes the formation of oxygen radicals via the Fenton reaction, which causes protein denaturation, DNA breakage, etc. Iron acquisition and homeostasis are tightly regulated in a cell
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