This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Heymann, P. Articles by Ernst, J. F. Search for Related Content PubMed PubMed Citation Articles by Heymann, P. Articles by Ernst, J. F.

The Siderophore Iron Transporter of Candida albicans (Sit1p/Arn1p) Mediates Uptake of Ferrichrome-Type Siderophores and Is Required for Epithelial Invasion

Institut für Mikrobiologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf,¹ Institut für Mikrobiologie und Biotechnologie, Universität Tübingen, Tübingen,² Dermatologische Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilian-Universität München, Munich, Germany,³ Unité de Mycologie Moléculaire, Institut Pasteur, Paris Cedex 15, France⁴

Received 24 April 2002/ Returned for modification 30 May 2002/ Accepted 12 June 2002

The human fungal pathogen Candida albicans contains a close homologue of yeast siderophore transporters, designated Sit1p/Arn1p. We have characterized the function of SIT1 in C. albicans by constructing sit1 deletion strains and testing their virulence and ability to utilize a range of siderophores and other iron complexes. sit1 mutant strains are defective in the uptake of ferrichrome-type siderophores including ferricrocin, ferrichrysin, ferrirubin, coprogen, and triacetylfusarinine C. A mutation of FTR1 did not impair the use of these siderophores but did affect the uptake of ferrioxamines E and B, as well as of ferric citrate, indicating that their utilization was independent of Sit1p. Hemin was a source of iron for both sit1 and ftr1 mutants, suggesting a pathway of hemin uptake distinct from that of siderophores and iron salts. Heterologous expression of SIT1 in the yeast Saccharomyces cerevisiae confirmed the function of Sit1p as a transporter for ferrichrome-type siderophores. The sit1 mutant was defective in infection of a reconstituted human epithelium as a model for human oral mucosa, while the SIT1 strain was invasive. In contrast, both sit1 and SIT1 strains were equally virulent in the mouse model of systemic infection. These results suggest that siderophore uptake by Sit1p/Arn1p is required in a specific process of C. albicans infection, namely epithelial invasion and penetration, while in the blood or within organs other sources of iron, including heme, may be used.

Editor: T. R. Kozel

This article has been cited by other articles:

• Baek, Y.-U., Li, M., Davis, D. A. (2008). Candida albicans Ferric Reductases Are Differentially Regulated in Response to Distinct Forms of Iron Limitation by the Rim101 and CBF Transcription Factors. Eukaryot Cell 7: 1168-1179 [Abstract] [Full Text]  
• Miethke, M., Marahiel, M. A. (2007). Siderophore-Based Iron Acquisition and Pathogen Control. Microbiol. Mol. Biol. Rev. 71: 413-451 [Abstract] [Full Text]  
• Kragl, C., Schrettl, M., Abt, B., Sarg, B., Lindner, H. H., Haas, H. (2007). EstB-Mediated Hydrolysis of the Siderophore Triacetylfusarinine C Optimizes Iron Uptake of Aspergillus fumigatus. Eukaryot Cell 6: 1278-1285 [Abstract] [Full Text]  
• Fernandez-Arenas, E., Cabezon, V., Bermejo, C., Arroyo, J., Nombela, C., Diez-Orejas, R., Gil, C. (2007). Integrated Proteomics and Genomics Strategies Bring New Insight into Candida albicans Response upon Macrophage Interaction. Mol. Cell. Proteomics 6: 460-478 [Abstract] [Full Text]  
• Tangen, K. L., Jung, W. H., Sham, A. P., Lian, T., Kronstad, J. W. (2007). The iron- and cAMP-regulated gene SIT1 influences ferrioxamine B utilization, melanization and cell wall structure in Cryptococcus neoformans. Microbiology 153: 29-41 [Abstract] [Full Text]  
• Prasad, T., Chandra, A., Mukhopadhyay, C. K., Prasad, R. (2006). Unexpected Link between Iron and Drug Resistance of Candida spp.: Iron Depletion Enhances Membrane Fluidity and Drug Diffusion, Leading to Drug-Susceptible Cells. Antimicrob. Agents Chemother. 50: 3597-3606 [Abstract] [Full Text]  
• Eichhorn, H., Lessing, F., Winterberg, B., Schirawski, J., Kamper, J., Muller, P., Kahmann, R. (2006). A Ferroxidation/Permeation Iron Uptake System Is Required for Virulence in Ustilago maydis. Plant Cell 18: 3332-3345 [Abstract] [Full Text]  
• Knight, S. A. B., Vilaire, G., Lesuisse, E., Dancis, A. (2005). Iron Acquisition from Transferrin by Candida albicans Depends on the Reductive Pathway. Infect. Immun. 73: 5482-5492 [Abstract] [Full Text]  
• Rouabhia, M., Schaller, M., Corbucci, C., Vecchiarelli, A., Prill, S. K.-H., Giasson, L., Ernst, J. F. (2005). Virulence of the Fungal Pathogen Candida albicans Requires the Five Isoforms of Protein Mannosyltransferases. Infect. Immun. 73: 4571-4580 [Abstract] [Full Text]  
• Lee, R. E. B., Liu, T. T., Barker, K. S., Lee, R. E., Rogers, P. D. (2005). Genome-wide expression profiling of the response to ciclopirox olamine in Candida albicans. J Antimicrob Chemother 55: 655-662 [Abstract] [Full Text]  
• Bernier, G., Girijavallabhan, V., Murray, A., Niyaz, N., Ding, P., Miller, M. J., Malouin, F. (2005). Desketoneoenactin-Siderophore Conjugates for Candida: Evidence of Iron Transport-Dependent Species Selectivity. Antimicrob. Agents Chemother. 49: 241-248 [Abstract] [Full Text]  
• Schrettl, M., Bignell, E., Kragl, C., Joechl, C., Rogers, T., Arst, H. N. Jr., Haynes, K., Haas, H. (2004). Siderophore Biosynthesis But Not Reductive Iron Assimilation Is Essential for Aspergillus fumigatus Virulence. J. Exp. Med. 200: 1213-1219 [Abstract] [Full Text]  
• Lorenz, M. C., Bender, J. A., Fink, G. R. (2004). Transcriptional Response of Candida albicans upon Internalization by Macrophages. Eukaryot Cell 3: 1076-1087 [Abstract] [Full Text]  
• Missall, T. A., Lodge, J. K., McEwen, J. E. (2004). Mechanisms of Resistance to Oxidative and Nitrosative Stress: Implications for Fungal Survival in Mammalian Hosts. Eukaryot Cell 3: 835-846 [Full Text]  
• Serrano, R., Bernal, D., Simon, E., Arino, J. (2004). Copper and Iron Are the Limiting Factors for Growth of the Yeast Saccharomyces cerevisiae in an Alkaline Environment. J. Biol. Chem. 279: 19698-19704 [Abstract] [Full Text]  
• Pierwola, A., Krupinski, T., Zalupski, P., Chiarelli, M., Castignetti, D. (2004). Degradation Pathway and Generation of Monohydroxamic Acids from the Trihydroxamate Siderophore Deferrioxamine B. Appl. Environ. Microbiol. 70: 831-836 [Abstract] [Full Text]  
• Pelletier, B., Beaudoin, J., Philpott, C. C., Labbe, S. (2003). Fep1 represses expression of the fission yeast Schizosaccharomyces pombe siderophore-iron transport system. Nucleic Acids Res 31: 4332-4344 [Abstract] [Full Text]  
• Santos, R., Buisson, N., Knight, S., Dancis, A., Camadro, J.-M., Lesuisse, E. (2003). Haemin uptake and use as an iron source by Candida albicans: role of CaHMX1-encoded haem oxygenase. Microbiology 149: 579-588 [Abstract] [Full Text]