The YeastCandida albicansBinds Complement Regulators Factor H and FHL-1

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Abstract
The human facultative pathogenic yeastCandida albicanscauses mucocutaneous infections and is the major cause of opportunistic fungal infections in immunocompromised patients.C. albicansactivates both the alternative and classical pathway of the complement system. The aim of this study was to assay whetherC. albicansbinds 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 toC. albicansby 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 yeastC. albicansis able to regulate alternative complement activation at its surface and to inactivate toxic complement activation products.