Germ tubes and proteinase activity contribute to virulence of Candida albicans in murine peritonitis

Peritonitis with Candida albicans is an important complication of bowel per foration and continuous ambulatory peritoneal dialysis. To define potential virulence factors, we investigated 50 strains of C. albicans in a murine p eritonitis model. There was considerable variation in their virulence in th is model when virulence was measured as release of organ-specific enzymes i nto the plasma of infected mice. Alanine aminotransferase (ALT) and alpha-a mylase (AM) were used as parameters for damage of the liver and pancreas, r espectively. The activities of ALT and AM in the plasma correlated with inv asion into the organs measured in histologic sections and the median germ t ube length induced,vith serum in vitro. When the activity of proteinases wa s inhibited in vivo with pepstatin A, there was a significant reduction of ALT and AM activities. This indicates that proteinases contributed to virul ence in this model. Using strains of C. albicans with disruption of secrete d aspartyl proteinase gene SAP1, SAP2, SAP3, or SAP4 through SAP6 (collecti vely referred to as SRP4-6), we showed that only a Delta sap4-6 triple muta nt induced a significantly reduced activity of ALT in comparison to the ref erence strain. In contrast to the Delta sap1, Delta sap2, and Delta sap3 mu tants, the ALT induced by the Delta sap4-6 mutant could not be further redu ced by pepstatin A treatment, which indicates that Sap4-6 may contribute to virulence in this model.