title: Identification of a Candida albicans ferrichrome transporter and its characterization by expression in Saccharomyces cerevisiae.
abstract: Saccharomyces cerevisiae can accumulate iron through the uptake of siderophore-iron. Siderophore-iron uptake can occur through the reduction of the complex and the subsequent uptake of iron by the high affinity iron transporter Fet3p/Ftr1p. Alternatively, specific siderophore transporters can take up the siderophore-iron complex. The pathogenic fungus Candida albicans can also take up siderophore-iron. Here we identify a C. albicans siderophore transporter, CaArn1p, and characterize its activity. CaARN1 is transcriptionally regulated in response to iron. Through expression studies in S. cerevisiae strains lacking endogenous siderophore transporters, we demonstrate that CaArn1p specifically mediates the uptake of ferrichrome-iron. Iron-ferrichrome and gallium-ferrichrome, but not desferri-ferrichrome, could competitively inhibit the uptake of iron from ferrichrome. Uptake of siderophore-iron resulting from expression of CaARN1 under the control of the MET25-promoter in S. cerevisiae was independent of the iron status of the cells and of Aft1p, the iron-sensing transcription factor. These studies demonstrate that the expression of CaArn1p is both necessary and sufficient for the nonreductive uptake of ferrichrome-iron and suggests that the transporter may be the only required component of the siderophore uptake system that is regulated by iron and Aft1p.
authors.affiliation: Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132, USA.
authors.forename: O
authors.initials: O
authors.lastname: Ardon
authors.forename: H
authors.initials: H
authors.lastname: Bussey
authors.forename: C
authors.initials: C
authors.lastname: Philpott
authors.forename: D M
authors.initials: DM
authors.lastname: Ward
authors.forename: S
authors.initials: S
authors.lastname: Davis-Kaplan
authors.forename: S
authors.initials: S
authors.lastname: Verroneau
authors.forename: B
authors.initials: B
authors.lastname: Jiang
authors.forename: J
authors.initials: J
authors.lastname: Kaplan
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D015152:Blotting, Northern; D015153:Blotting, Western; D002176:Candida albicans / Q000737:chemistry* / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D027682:Cation Transport Proteins; D004305:Dose-Response Relationship, Drug; D005291:Ferrichrome / Q000378:metabolism*; D005656:Fungal Proteins; D007501:Iron / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D017262:Siderophores / Q000493:pharmacokinetics
chemical_list: C442225:ARN1 protein, Candida albicans; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D005656:Fungal Proteins; D017262:Siderophores; D005291:Ferrichrome; D008715:Methionine; D007501:Iron