Characterization and Functional Analysis of the Siderophore-Iron Transporter CaArn1p in Candida albicans

• Published in: The Journal of biological chemistry 2002-08, Vol.277 (34), p.30598-30605
• Main Authors: Hu, Chuan-Jiong, Bai, Chen, Zheng, Xin-De, Wang, Yan-Ming, Wang, Yue
• Format: Article
• Language: English
• Subjects: Animals; Candida albicans - growth & development; Candida albicans - metabolism; Candida albicans - pathogenicity; Carrier Proteins - analysis; Carrier Proteins - genetics; Carrier Proteins - physiology; Cation Transport Proteins; Female; Fungal Proteins; Gene Expression Regulation - drug effects; Iron - pharmacology; Mice; Mice, Inbred BALB C; RNA, Messenger - analysis
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M204545200

Siderophores are small organic compounds with high affinity for ferric iron. Microorganisms commonly acquire iron via siderophore secretion and uptake. Here we report the characterization of the siderophore transporter CaArn1p in the fungal pathogen Candida albicans . Deletion of CaARN1 reduced the ability of C. albicans to use iron bound to the hydroxamate-type siderophore ferrichrome and abolished it when two high-affinity iron permease genes ( CaFTR1 and CaFTR2 ) were also deleted, indicating a role of CaArn1p as well as the permeases in ferrichrome-iron uptake. Caarn1Δ (but not Caftr1ΔCaftr2Δ ) assimilated iron from another hydroxamate-type siderophore, ferrioxamine B, suggesting that iron uptake from this compound depends on the permeases, but not on CaArn1p. Northern blot analysis revealed that the transcription repressor CaTup1p repressed CaARN1 expression under iron-replete conditions via the DNA-binding protein Rfg1p. Green fluorescent protein-tagged CaArn1p was observed predominantly in the plasma membrane, with some in the cytoplasm as distinct spots. The number of these spots increased with the increase in ferrichrome concentration, suggesting that CaArn1p internalization might be a mechanism for ferrichrome-iron uptake or for recycling the transporter. Caarn1Δ did not show reduced virulence when injected into the blood stream of mice, implying that CaArn1p is not required for iron uptake along this route of infection.