Reduced expression of the functionally active complement receptor for iC3b but not for C3d on an avirulent mutant of Candida albicans

Abstract

Pseudohyphae of Candida albicans bear surface receptors for iC3b and C3d. In order to determine a possible role for these receptors in the pathogenesis of candidiasis, a spontaneous C. albicans mutant, m-10, which exhibits reduced ability to adhere in vitro to fibrin platelet clots and epithelial cells or to cause endocarditis in a rabbit model, and its parent wild-type (wt) strain were compared for receptor expression in rosetting assays with sheep erythrocytes carrying iC3b (EAC1423bi) or C3d (EAC1423d). An equally high attachment to wt and m-10 was seen with EAC1423d, whereas rosetting with EAC1423bi was reduced by 53% in m-10 compared with wt. In inhibition studies, rosetting of wt with EAC1423bi was markedly inhibited by culture filtrate, hyphal-cell extract, and DEAE-fractionated material prepared from wt (54, 87, and 70% decreases in rosetting, respectively), thus suggesting the presence of the soluble, functionally active iC3b receptor of C. albicans in each of these preparations. Minimal inhibition of iC3b rosetting, however, was seen with the identical materials from m-10 (21, 5, and 12%, respectively). All of the preparations from the two strains were equally effective in their inhibitory activities against rosetting of C3d. A human serum specimen obtained from a patient with chronic mucocutaneous candidiasis blocked iC3b rosetting of the wt strain almost completely. When used in an immunoblot, this serum recognized proteins of 68 to 71, 55, and 50 kilodaltons (kDa) in hyphal-cell extracts of the wt. With the same preparation of the avirulent mutant, only weak reactions with the 68to 71-kDa and 55-kDa proteins occurred, while the 50-kDa protein was not detectable. Taken together, these results indicate that the expression of the functionally active iC3b receptor on C. albicans may be involved in the virulence of the organism, possibly by mediating adherence to mammalian cells.

Complement and fungal pathogens: an update

“…57,58 Virulent strains of C. albicans produce higher amounts of the CR3-homologue than avirulent mutants, and the expression of the cloned molecule in Saccharomyces cerevisiae leads to the adhesion of this normally nonadherent yeast to human epithelial cells. 59,60 An additional role for the fungal CR3-like protein was proposed by Moors et al [61] by binding C. albicans cells to erythrocytes, it might help to acquire the vitally important iron out of blood ( Fig. 2).…”

Bacteria-phagocyte interactions: emerging tactics in an ancient rivalry

“…Thus, the C3bi opsonin may be diverted away from phagocytes onto Candida expressing CR3 [23,24]. Alternatively, this functionally active CR3 receptor on Candida aibicans, as a member of the integrin receptor superfamily, may mediate the attachment of Candida to mammafian cells [25].…”

Coordination of germ tube formation and surface antigen expression in Candida albicans

“…The difficulty of obtaining mutant phenotypes in diploid organisms such as C. albicans and the concomitant loss and regain of germ tube formation and surface expression of certain antigens suggested that a single locus was involved. Mutants deficient in binding iC3b and C3d, activities preferentially expressed on hyphal extensions, are able to form germ tubes [20][21] and thus germ tube formation is not dependent on expression of either of these determinants. On the other hand conditions which inhibit synthesis [22] or deposition [11] of a putative structural protein of the hyphal wall reduce germ tube formation and suggest that synthesis of one or more preferentially expressed proteins is not dispensable.…”