Iron acquisition by Cryptococcus neoformans

Abstract

Iron is an essential element for the growth and metabolism of microbial cells. Most pathogenic microbes elaborate powerful iron chelating agents (siderophores) to mobilize iron from ferric ligands. The pathogenic yeast, Cryptococcus neoformans has not been found to produce siderophores and its mechanism of iron acquisition is unknown. This investigation explored an alternative pathway for iron acquisition by examining the interactions of iron with the cell surface. Iron uptake experiments were conducted utilizing radiolabelled ferrous iron and ferric iron chelates, with evidence for the presence of iron(ii) receptors and the generation of ferrous iron by surface reduction. Hyperbolic kinetics were found when ⁵⁹Feⁱⁱ was presented to the organism and uptake was blocked with bathophenanthroline sulphonate, an Fe²⁺ chelator. The yeast also acquired iron as [⁵⁹Fe³⁺]-citrate and [⁵⁹Fe³⁺]-pyrophosphate while bathophenanthroline sulphonate reduced the acquisition of these ferric ligands by 48% and 52% respectively. Pre-incubation with either ferric ligand also reduced iron acquisition by 50%. KCN inhibited uptake of iron(ii) by 90% and uptake of [⁵⁹Fe³⁺]-pyrophosphate and [⁵⁹Fe³⁺]-citrate by 46% and 56% respectively; dinitrophenol had no effect on these processes. The data suggest that C. neoformans can (i) generate ferrous iron at the cell surface via a reduction of ferric chelates, with the subsequent acquisition of the ferrous iron, and (ii) acquire iron through the interaction of ferric chelates with a surface component.