Roles of Candida albicans aspartic proteases in host-pathogen interactions

Candida albicans—a common opportunistic fungal pathogen of humans—causes serious, disseminated invasive infections (candidiases) executed due to the action of several groups of virulence factors. One of the most critical is a family of secreted aspartic proteases involved in the destruction of host proteins and tissues. This chapter aims to characterize biochemical and structural properties of these enzymes that determine their functions and summarize their specific roles in the development and propagation of fungal infections. Candidal aspartic proteases deregulate the host biochemical homeostasis, by impairing the major proteolytic cascades such as the blood coagulation, the kallikrein-kinin system, and the complement system, by unleashing the activity of host proteases due to the degradation of specific endogenous inhibitors and by the inactivation of antimicrobial peptides and proteins produced by host cells. The degradation of important host proteins influences the fungal adhesion to the host cell surfaces, promotes the subsequent tissue damages, and enables the further dissemination of the pathogen. Confirmed multiple roles of candidal aspartic proteases in the host-pathogen interactions during candidiasis qualify these enzymes as promising potential targets for novel antifungal therapies.