Infections with Candida albicans rank as a leading cause of morbidity and mortality in the acquired immunodeficiency syndrome. Conditions such as neutrophil dysfunction or hyperglycemia in the host, or transformation of the organism from yeast to mycelial phase, significantly augment the risk of infection and invasion, but the reasons for this increased pathogenicity are unknown. We have recently described a receptor for human complement fragment iC3b on the surface of Candida albicans. This receptor shares homology with the alpha chain --- but not with the beta chain --- of the neutrophil receptor for iC3b (neutrophil CR3), as determined by the binding of monoclonal antibodies and flow cytometric analysis. The binding of iC3b, the preferred ligand for neutrophil CR3, occurs noncovalently at the yeast receptor site and has a Ka of 2.45 x 106 L/M which is identical to that for neutrophil CR3. Mycelia transformation of receptor-bearing strains of C. albicans, as well as high glucose concentrations (50 mM) significantly augment expression of the candidal receptor, as assessed both by specific binding of iC3b and by indirect immunofluorescence for cross-reacting monoclonals to the alpha chain of CR3. We have previously shown that covalent attachment of iC3b to the microbial surface is a necessary requirement for phagocytosis. Because the candidal receptor binds iC3b noncovalently, the receptor subverts opsonization and prevents phagocytic recognition. The candidal receptor thus provides a molecular mechanism by which to analyze the pathogenesis of infections with Candida albicans. Three aspects of study are proposed: (10 Biochemical characterization of receptor by enzymatic digestion, cellular localization, and protein purification. (2) Expanded functional characterization by quantitation of covalent and noncovalent binding sites for iC3b and by measurement of calcium flux; and (3) Clinical characterization of the importance of the receptor as a marker for invasive candidiasis by quantitation of receptor density on pathogenic isolates and by the development of an ELISA assay to permit the rapid diagnosis of invasive Candida infections. These studies should clarify the role of the candidal receptor both as a molecular marker for the pathogenicity of this organism and as a potential tool for the rapid diagnosis of invasive candidemia.
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