Proteolytic Cleavage of Various Human Serum Proteinase Inhibitors by Candida albicans Aspartic Proteinase

Abstract

The secreted Candida albicans aspartic proteinase (SAP) is presumed to be one of the putative Candida virulence factors, while serum proteinase inhibitors depend on host defense mechanisms. We examined the interaction between SAP and serum proteinase inhibitors, such as C1-inhibitor, α2 plasmin inhibitor, and antithrombin III. SAP progressively inactivated plasmin inhibitory activity of C1-inhibitor and α2 plasmin inhibitor. It also inactivated thrombin inhibitory activity of antithrombin III. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, these host proteinase inhibitors were progressively degraded by SAP during prolonged incubation. These results suggest that SAP induces an imbalance of complements, coagulation and fibrinolytic systems through the degradation and inactivation of these host proteinase inhibitors, and that SAP may play an important role in the development of Candida albicans infections