Candida albicans proteinases: resolving the mystery of a gene family.

Fungal infections of mucosal surfaces are extremely common, debilitating and often recurring diseases, which are frequently caused by the yeast Candida albicans. Furthermore, in the severely immunocompromised host, C. albicans may also cause deepseated or even life-threatening systemic infections. In order to colonize, infect and evade host defence mechanisms, C. albicans possesses a repertoire of virulence attributes. In particular, the secreted aspartic proteinases (Saps), encoded by the SAP gene family with ten members, appear to play a major role in C. albicans virulence. The SAP family is differentially regulated and distinct members are expressed under a variety of laboratory growth conditions and during experimental C. albicans infections in vitro and in vivo. The contribution of the Saps to C. albicans pathogenesis has been clearly demonstrated using SAP-deficient mutants and proteinase inhibitors. These studies demonstrated that different SAP genes appear to be crucial for mucosal and systemic infections, and are involved in C. albicans adherence, tissue damage and evasion of host immune responses. Therefore, the Sap isoenzymes appear to have a variety of functions in vivo, which are probably called upon at different stages and in different types of C. albicans infection. This review aims to summarize the more recent data regarding the contribution of the secreted proteinases to C. albicans virulence and strives to explain why C. albicans possesses such a gene family.