Description:
<jats:title>ABSTRACT</jats:title>
<jats:p>
Peritonitis with
<jats:italic>Candida albicans</jats:italic>
is an important complication of bowel perforation and continuous ambulatory peritoneal dialysis. To define potential virulence factors, we investigated 50 strains of
<jats:italic>C. albicans</jats:italic>
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 of
<jats:italic>C. albicans</jats:italic>
with disruption of secreted aspartyl proteinase gene
<jats:italic>SAP1</jats:italic>
,
<jats:italic>SAP2</jats:italic>
,
<jats:italic>SAP3</jats:italic>
, or
<jats:italic>SAP4</jats:italic>
through
<jats:italic>SAP6</jats:italic>
(collectively referred to as
<jats:italic>SAP4-6</jats:italic>
), we showed that only a Δ
<jats:italic>sap4-6</jats:italic>
triple mutant induced a significantly reduced activity of ALT in comparison to the reference strain. In contrast to the Δ
<jats:italic>sap1</jats:italic>
, Δ
<jats:italic>sap2</jats:italic>
, and Δ
<jats:italic>sap3</jats:italic>
mutants, the ALT induced by the Δ
<jats:italic>sap4-6</jats:italic>
mutant could not be further reduced by pepstatin A treatment, which indicates that Sap4-6 may contribute to virulence in this model.
</jats:p>