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Infection and Immunity, September 2002, p. 5246-5255, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5246-5255.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Petra Heymann,1,2 Michaela Gerads,1 Martin Schaller,3 Francoise Dromer,4 Günther Winkelmann,2 and Joachim F. Ernst1*

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.

* Corresponding author. Mailing address: Institut für Mikrobiologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1/26.12, D-40225 Düsseldorf, Germany. Phone and fax: 49 211 8115176. E-mail: joachim.ernst{at}uni-duesseldorf.de.

Editor: T. R. Kozel

Infection and Immunity, September 2002, p. 5246-5255, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5246-5255.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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