Cell Surface Glycosaminoglycans as Receptors for Adhesion of Candida spp. to Corneal Cells

Abstract

The most common causal agents of fungal keratitis are yeasts of the Candida genus. Adhesion constitutes the first stage of pathogenesis. Previous studies have shown that glycosaminoglycans from the corneal cell surface play an essential role in bacterial keratitis, although little is known about their role in fungal infections. The objective of this work is to analyze the role that glycosaminoglycans (GAGs) play in the adhesion of fungi of the Candida genus to corneal epithelial cells. The participation of GAGs in the adhesion of fungi was studied through the specific inhibition of the synthesis of these molecules by enzymatic digestion using specific lyases and the silencing of various genes involved in heparan sulfate sulfation. The results seem to indicate that glycosaminoglycans act to some extent as receptors for this fungus, although there are differences between fungal species. Treatment with inhibitors partially reduced the adherence of fungal species. Digestion of cell surface heparan sulfate further reduced the adherence of Candida albicans and Candida glabrata compared to chondroitin sulfate, indicating that the binding is preferentially mediated by heparan sulfate. Degradation of both heparan sulfate and chondroitin sulfate produced similar effects on the adherence of Candida parapsilosis. However, adhesion of C. albicans hyphae is not dependent on GAGs, suggesting the expression of other adhesins and the recognition of other receptors present in corneal cells. Our results open the door to new strategies for stopping the adhesion of pathogenic fungi, and their subsequent invasion of the cornea; thus, reducing the probability of the keratitis development.

Keywords

• fungal keratitis
• cornea
• glycosaminoglycan
• heparan sulfate
• chondroitin sulfate