Distinct domains of the Candida albicans adhesin Eap1p mediate cell-cell and cell-substrate interactions.

The adhesion of Candida albicans to host tissues contributes to its virulence, and adhesion to tissues or medical devices is a necessary step in biofilm formation. EAP1 encodes a glycosylphosphatidylinositol (GPI)-anchored glucan-cross-linked cell wall protein that mediates adhesion of C. albicans to various materials and cells, and appears to be required for C. albicans biofilm formation in vitro and in vivo. In this study, we demonstrated that the Eap1p N-terminal signal peptide and C-terminal GPI-anchor sequences result in similar protein localization in Saccharomyces cerevisiae and C. albicans. To investigate the contribution of different Eap1p domains to adhesion, we expressed Eap1p domain deletion mutants in non-adherent S. cerevisiae strains. The N-terminal domain mediates yeast cell-cell adhesion and invasive growth. Two Ser/Thr-rich domains containing tandem repeats were required to project the N-terminal region into the extracellular environment and to mediate adhesion to polystyrene. The N-terminal tandem repeat domain mediated adhesion to mammalian epithelial cells and promoted S. cerevisiae pseudohyphal growth. These results suggest a modular structure of Eap1p in which each domain serves multiple, often distinct, functions.