(451f) The Candida Albicans Adhesion Receptor Eap1 Regulates Adhesion and Biofilm Formation in Vitro and in Vivo

Candida albicans is the most commonly isolated fungal pathogen of humans. C. albicans is an opportunistic organism, predominantly causing topical or mucosal infections. However, in immune-compromised persons, systemic bloodstream infections can occur. Most often, these infections are associated with a C. albicans biofilm on an implanted medical device, such as a central venous catheter. We screened a C. albicans genomic DNA library for genes that caused an adhesin-deficient Saccharomyces cerevisiae strain to adhere to polystyrene. This screen identified a novel adhesion receptor, EAP1, which encodes a GPI-anchored glucan cross-linked cell wall protein. We will show that EAP1 localizes to the cell wall and permits C. albicans adhesion to a variety of materials used in medical devices, as well as to mammalian cells. Also, EAP1 expression affects cell morphogenesis, another C. albicans virulence factor. Disrupting EAP1 suppressed filamentation in response to particular stimuli and autonomous expression of EAP1 restored filamentation in a strain lacking Efg1, a transcriptional regulator of dimorphic growth. Furthermore, EAP1 expression was required for C. albicans biofilm formation in vitro and in an in vivo rat central venous catheter model. Expression of EAP1 was also upregulated in the biofilm-associated cells. Together, these results suggest that EAP1 is a promising molecular target for inhibiting C. albicans biofilm formation and the associated virulence.