Recognition of endothelial cells byCandida albicans: role of complement-binding proteins

Abstract

Candida albicans, a commensal of humans, can cause either mucosal or systemic infections. The virulence properties of the organism include cell-surface adhesins that recognize ligands of host cells. Hyphal forms of the organism possess a 60-kDa mannoprotein that recognizes a variety of host-cell ligands including the complement C3 conversion products, C3bi and C3d. In addition, a protein of similar molecular mass also binds to endothelial extracellular matrix proteins such as laminin and fibronectin. While the 60-kDa protein is associated with the cell surface of hyphal forms of the organism, a protein of 50 kDa with similar ligand-binding activities is associated with the plasma membrane of blastoconidia. This protein cross reacts with antibodies to the 60-kDa protein. Isolation of the gene(s) encoding these cell-surface proteins is underway using both a human B-lymphocyte CR2 gene fragment or oligonucleotides based upon peptide sequence to screen libraries of C. albicans. Mutants of the organism with reduced expression of either C3d or C3bi-binding activity have been isolated. These strains are less virulent and also less adherent in vitro. Studies are currently underway to define the contribution of these proteins to the virulence of the organism. Key words: adherence, complement receptor, mannoprotein, virulence, ligand recognition.