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Infection and Immunity, September 2002, p. 5185-5192, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5185-5192.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Yeast Candida albicans Binds Complement Regulators Factor H and FHL-1

T. Meri,1,2 A. Hartmann,1 D. Lenk,1 R. Eck,1 R. Würzner,3 J. Hellwage,1 S. Meri,2 and P. F. Zipfel1*

Hans Knöll Institute for Natural Products Research, Jena, Germany,1 Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland,2 Institute for Hygiene and Social Medicine, University of Innsbruck, Innsbruck, Austria3

Received 12 March 2002/ Returned for modification 1 May 2002/ Accepted 25 May 2002

The human facultative pathogenic yeast Candida albicans causes mucocutaneous infections and is the major cause of opportunistic fungal infections in immunocompromised patients. C. albicans activates both the alternative and classical pathway of the complement system. The aim of this study was to assay whether C. albicans binds human complement regulators in order to control complement activation at its surface. We observed binding of two central complement regulators, factor H and FHL-1, from normal human serum to C. albicans by adsorption assays, immunostaining, and fluorescence-activated cell sorter (FACS) analyses. Specificity of acquisition was further confirmed in direct binding assays with purified proteins. The surface-attached regulators maintained their complement regulatory activities and mediated factor I-dependent cleavage of C3b. Adsorption assays with recombinant deletion mutant proteins were used to identify binding domains. Two binding sites were localized. One binding domain common to both factor H and FHL-1 is located in the N-terminal short consensus repeat domains (SCRs) 6 and 7, and the other one located in C-terminal SCRs 19 and 20 is unique to factor H. These data indicate that by surface acquisition of host complement regulators, the human pathogenic yeast C. albicans is able to regulate alternative complement activation at its surface and to inactivate toxic complement activation products.

* Corresponding author. Mailing address: Department of Infection Biology, Hans Knöll Institute for Natural Products Research, Beutenbergstrasse 11a, Jena, Germany. Phone: 49 (03641) 656 900. Fax: 49 (03641) 656 902. E-mail: zipfel{at}pmail.hki-jena.de.

Editor: W. A. Petri, Jr.

Infection and Immunity, September 2002, p. 5185-5192, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5185-5192.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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