title: Ferric iron reduction by Cryptococcus neoformans.
abstract: The pathogenic yeast Cryptococcus neoformans must reduce Fe(III) to Fe(II) prior to uptake. We investigated mechanisms of reduction using the chromogenic ferrous chelator bathophenanthroline disulfonate. Iron-depleted cells reduced 57 nmol of Fe(III) per 10(6) cells per h, while iron-replete cells reduced only 8 nmol of Fe(III). Exponential-phase cells reduced the most and stationary-phase cells reduced the least Fe(III), independent of iron status. Supernatants from iron-depleted cells reduced up to 2 nmol of Fe(III) per 10(6) cells per h, while supernatants from iron-replete cells reduced 0.5 nmol of Fe(III), implying regulation of the secreted reductant(s). One such reductant is 3-hydroxyanthranilic acid (3HAA), which was found at concentrations up to 29 microM in iron-depleted cultures but <2 microM in cultures supplemented with iron. Moreover, when washed and resuspended in low iron medium, iron-depleted cells secreted 20.4 microM 3HAA, while iron-replete cells secreted only 4.5 microM 3HAA. Each mole of 3HAA reduced 3 mol of Fe(III), and increasing 3HAA concentrations correlated with increasing reducing activity of supernatants; however, 3HAA accounted for only half of the supernatant's reducing activity, indicating the presence of additional reductants. Finally, we found that melanized stationary-phase cells reduced 2 nmol of Fe(III) per 10(6) cells per h--16 times the rate of nonmelanized cells--suggesting that this redox polymer participates in reduction of Fe(III).
authors.affiliation: Department of Internal Medicine, Virginia Commonwealth University, Richmond 23298-0049, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Nyhus
authors.forename: A T
authors.initials: AT
authors.lastname: Wilborn
authors.forename: E S
authors.initials: ES
authors.lastname: Jacobson
mesh_terms: D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism; D002474:Cell-Free System / Q000378:metabolism / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000254:growth & development / Q000378:metabolism*; D038181:FMN Reductase; D005290:Ferric Compounds / Q000378:metabolism*; D005296:Ferrous Compounds / Q000378:metabolism; D008543:Melanins / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D005290:Ferric Compounds; D005296:Ferrous Compounds; D008543:Melanins; D015095:3-Hydroxyanthranilic Acid; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases; C023903:ferric citrate iron reductase