Different adhesins for type IV collagen on Candida albicans:: identification of a lectin-like adhesin recognizing the 7S(IV) domain

Adherence of the opportunistic pathogen Candida albicans to basement membrane (BM) proteins is considered a crucial step in the development of candidiasis. In this study the interactions of C. albicans yeast cells with the three main domains of type IV collagen, a major BM glycoprotein, were analysed. C. albicans adhered to the three immobilized domains by different mechanisms. Adhesion to the N-terminal cross-linking domain (7S) required the presence of divalent cations, whereas interaction with the central collagensus domain (CC) was cation-independent. Recognition of the C-terminal noncollagenous domain (NCI) was partially cation-dependent. Binding inhibition assays with the corresponding domains in soluble form showed that these interactions were specific. Both Ca2+ and Mg2+ promoted adhesion to the 75 domain and the interaction was completely abolished by EDTA. Treatment of the 75 domain, or its subunits, with N-glycosidase F reduced yeast binding by approximately 70%. Moreover, several sugars known to be part of the N-linked oligosaccharide chains of collagen IV inhibited adhesion to immobilized 7S; N-acetylglucosamine, L-fucose and methylmannoside caused a similar inhibition whereas N-acetyllactosamine was a more effective inhibitor. In contrast, glucose, galactose, lactase or heparan sulfate did not affect yeast binding. Combinations of the inhibitory sugars at suboptimal inhibition concentrations did not reduce C. albicans adhesion snore than the individual sugars, pointing to a single lectin as responsible for the interaction. These results taken together show that C. albicans utilizes several adhesins for interacting with type IV collagen, and that at least one of them is a lectin which recognizes the 75(IV) oligosaccharide residues as its receptor.