News from the Fungal Front: Wall Proteome Dynamics and Host–Pathogen Interplay

In Candida albicans, like in Saccharomyces cerevisiae, the basal layer of the mature cell wall consists of a network of β-1,3- and β-1,6-glucans and chitin and functions as a skeletal layer. This basal layer is covered by an external layer of highly glycosylated, covalently anchored wall proteins radiating from the cell surface, which are directly involved in the first contacts between the fungal pathogen and host cells. The majority of the covalently bound wall proteins are modular glycosylphosphatidylinositol (GPI)-proteins. In their final form, wall-bound GPI-proteins usually consist of a C-terminal, truncated GPI-anchor that attaches them to the β-glucan layer, followed by a heavily glycosylated serine/threonine-rich spacer domain that often includes repeats, and an N-terminally located functional domain protruding from the cell surface [1]. At any given time-point >20 different covalently bound wall proteins can be identified [2], [3] that are involved in processes such as adhesion, biofilm formation, wall remodeling, iron acquisition, and coping with immune responses. Importantly, the wall proteome is highly dynamic and continuously adapts to the specific conditions that C. albicans encounters in the host environment. In this review we examine the role of wall proteins in infection-related processes and assess their potential as targets for antifungal and vaccine development.