Phosphoglycerate mutase and methionine synthase act as adhesins of Candida albicans to the corneal epithelium, altering their expression during the tissue adhesion process.

The yeast form of Candida albicans uses glycosaminoglycans (GAGs), primarily heparan sulfate, as adhesion receptors for corneal epithelial cells. However, during the transition to the hyphal form, the fungus shifts to using alternative receptors. This study aims to identify fungal adhesins involved in GAG binding and examine their expression dynamics during tissue adhesion. Using chromatography, three proteins from the C. albicans cell wall with high affinity for heparin were identified: methionine synthase, phosphoglycerate mutase, and cytochrome c. These proteins were overexpressed in Escherichia coli and tested in adhesion assays. Methionine synthase and phosphoglycerate mutase partially inhibited yeast adhesion to corneal epithelial cells in a concentration-dependent manner, while cytochrome c enhanced adhesion. Transcriptional analysis of the genes encoding these proteins (MET6, GMP1, and CYC1), along with other genes related to adhesion and yeast-to-hypha transition (ALS3, HWP1, and INT1), revealed that exposure to exosomes or GAGs increased GMP1, CYC1, and ALS3 expression, while reducing HWP1 and INT1. In contrast, direct contact with epithelial cells decreased MET6 and GMP1 expression, but increased HWP1 expression. These results suggest that methionine synthase and phosphoglycerate mutase act as adhesins for GAGs, with their expression modulated by GAG or exosome interaction to promote adhesion. However, epithelial cell contact alters the expression of adhesins and molecules linked to hyphal formation, highlighting their dynamic role in corneal adhesion.