Parameters for determination of Candida albicans virulence in murine peritonitis

Using intraperitoneal (i.p.) infection of mice with Candida albicans we determined which parameters might be useful for characterization of virulence in this model. Upon i.p. infection of mice with two reference strains striking differences in lethality were detected. These differences in virulence corresponded with invasion of the liver and pancreas by the virulent strain and with a lack of invasion by the avirulent strain. The virulent strain was able to release high amounts of the enzymes alanine aminotransferase (ALT) and alpha-amylase (AM) from liver and pancreas into the blood plasma. Most likely, these enzymes were released by penetration of hyphae into the cytoplasm which was shown with electron microscopy. When invasion slowed down, there was also a drop in the activities of ALT and AM measured in the blood of infected mice. As both strains disseminated to the heart, kidneys, and lungs, dissemination into these organs was no reliable parameter for virulence in this model. However, only the virulent strain was able to reach the brain and to germinate in the kidneys and brain. In contrast to invasion and enzyme activities, the fungal load in the peritoneal cavity and in the neighbouring organs appeared not to be related with virulence. This may be concluded from the fact that there were no differences in the absolute colony forming units (cfu) and the length of persistence of both strains when similar inocula were used. We conclude that the ability of a given strain of C. albicans to invade neighbouring organs, to reach the brain upon dissemination and germination in the brain and kidneys may be used for measurement of virulence in this model when virulence is defined as lethality.