title: 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.
authors.affiliation: Department of Medical Specialties, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Vartivarian
authors.forename: R E
authors.initials: RE
authors.lastname: Cowart
authors.forename: E J
authors.initials: EJ
authors.lastname: Anaissie
authors.forename: T
authors.initials: T
authors.lastname: Tashiro
authors.forename: H A
authors.initials: HA
authors.lastname: Sprigg
mesh_terms: D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000378:metabolism*; D011756:Diphosphates / Q000378:metabolism; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007501:Iron / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D010618:Phenanthrolines / Q000494:pharmacology; D011190:Potassium Cyanide / Q000494:pharmacology
chemical_list: D002951:Citrates; D011756:Diphosphates; D007502:Iron Chelating Agents; D010618:Phenanthrolines; C017049:bathophenanthroline disulfonic acid; D019343:Citric Acid; C026058:EDDA; D004492:Edetic Acid; D007501:Iron; D011190:Potassium Cyanide; C049051:ferric pyrophosphate