Germ Tubes and Proteinase Activity Contribute to Virulence of Candida albicans in Murine Peritonitis

ABSTRACT Peritonitis with Candida albicans is an important complication of bowel perforation and continuous ambulatory peritoneal dialysis. To define potential virulence factors, we investigated 50 strains of C. albicans in a murine peritonitis model. There was considerable variation in their virulence in this model when virulence was measured as release of organ-specific enzymes into the plasma of infected mice. Alanine aminotransferase (ALT) and α-amylase (AM) were used as parameters for damage of the liver and pancreas, respectively. The activities of ALT and AM in the plasma correlated with invasion into the organs measured in histologic sections and the median germ tube length induced with serum in vitro. When the activity of proteinases was inhibited in vivo with pepstatin A, there was a significant reduction of ALT and AM activities. This indicates that proteinases contributed to virulence in this model. Using strains ofC. albicans with disruption of secreted aspartyl proteinase gene SAP1, SAP2, SAP3, orSAP4 through SAP6 (collectively referred to asSAP4-6), we showed that only a Δsap4-6 triple mutant induced a significantly reduced activity of ALT in comparison to the reference strain. In contrast to the Δsap1, Δsap2, and Δsap3 mutants, the ALT induced by the Δsap4-6 mutant could not be further reduced by pepstatin A treatment, which indicates that Sap4-6 may contribute to virulence in this model.

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