Roles of candida albicans aspartic proteases in host-pathogen interactions

Abstract

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