The yeast Candida albicans binds complement regulators factor H and FHL-1.
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.
Hans Knöll Institute for Natural Products Research, Jena, Germany.
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Hartmann
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Lenk
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Eck
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Würzner
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Hellwage
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Zipfel
D001665:Binding Sites / Q000235:genetics; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D002176:Candida albicans / Q000276:immunology* / Q000472:pathogenicity*; D003167:Complement Activation; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
D001798:Blood Proteins; C493495:CFH protein, human; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D011994:Recombinant Proteins; D017242:Complement Factor H; D006493:Heparin