Characterization of genes encoding for cell surface proteins induced during hostpathogen interaction

Candida albicans is a commensal organism living on skin and mucosal surfaces of humans. Its presence becomes a problem in immunocompromised patients where it may turn into an opportunistic pathogen. Candida colonizes various host niches including skin, gastrointestinal and the urogenital tract, which offer various environments in terms of pH and nutrient availability. The cell surface of the fungus is the site of direct interaction of Candida with the host, mediating the environmental sensing, adhesion and also interaction with the host immune system. Since the cell wall is not present in humans its components are a prime target for drug development. To reveal whether C. albicans is able to specifically react to different epithelial tissue or other surfaces in a specific manner we used transcriptional profiling in order to identify genes differentially regulated during adhesion focusing on cell surface proteins. One of the genes identified was termed Adhesion Upregulated Factor - AUF8. The respective protein is predicted to be localized in the plasma membrane carrying four transmembrane domains. AUF8 is upregulated in an adhesion dependent manner with the strongest induction on intestinal tissue model after two hours of interaction. For AUF8 we identified six homologues in the C. albicans genome, of which five together with AUF8 are in one 10 kb gene-cluster. When heterologously expressed in S. cerevisiae Auf8p is localized to the plasma membrane. Deletion studies indicate that the AUF genes may be required for fitness during stationary phase. However, its function during adhesion is still unclear. Other proteins encoded by genes upregulated during adhesion and first steps of invasion are localized in the cell wall. The functional studies of PGA7, PGA23 and PRA1 with regards to adhesion and invasion as well as cell wall stability were performed using deletion and overexpression strains. Our studies qualify PGA7 and PGA23 as structural elements of the cell wall rather than adhesins.