Identification of a Candida albicans ferrichrome transporter and its characterization by expression in Saccharomyces cerevisiae

Saccharomyces cerevisiae can accumulate iron through the uptake of sideroph ore-iron. Siderophore-iron uptake can occur through the reduction of the co mplex and the subsequent uptake of iron by the high affinity iron transport er Fet3p/Ftr1p. Alternatively, specific siderophore transporters can take u p the siderophore-iron complex. The pathogenic fungus Candida albicans can also take up siderophore-iron. Here we identify a C. albicans siderophore t ransporter, CaArn1p, and characterize its activity. CaARN1 is transcription ally regulated in response to iron. Through expression studies in S. cerevi siae strains lacking endogenous siderophore transporters, we demonstrate th at CaArn1p specifically mediates the uptake of ferrichrome-iron. Iron-ferri chrome and gallium-ferrichrome, but not desferri-ferrichrome, could competi tively inhibit the uptake of iron from ferrichrome. Uptake of siderophore-i ron resulting from expression of CaARN1 under the control of the MET25-prom oter in S. cerevisiae was independent of the iron status of the cells and o f Aft1p, the iron-sensing transcription factor. These studies demonstrate t hat the expression of CaArn1p is both necessary and sufficient for the non- reductive uptake of ferrichrome-iron and suggests that the transporter may be the only required component of the siderophore uptake system that is reg ulated by iron and Aft1p.