Parameters for determination of Candida albicans virulence in murine peritonitis

Abstract

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 α-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.

The Role of Secreted Aspartyl Proteinases inCandida albicansKeratitis

“…5,31,32 In contrast, SAP4, -5, and/or -6 influence the virulence of experimental disseminated candidiasis and candidal peritonitis. 3,4,16,33,34 Our study suggests that SAP6 is also involved in the pathogenesis of C. albicans keratitis.…”

Protein S-100B: A Serum Marker for Ischemic and Infectious Injury of Cerebral Tissue

“…This reactive astrogliosis is a prominent feature regularly found in brain tissue adjacent to an injury. These results confirm the usefulness of serum markers to reflect the invasion capacity of the fungi and the host response as it has recently been described (21,22). These results are in line with earlier work where activation of astrocytes could also be demonstrated in fungal and parasitic infection of the brain in humans and mice (19,20).…”

Functional analysis of a vacuolar ABC transporter in wild‐type Candida albicans reveals its involvement in virulence

“…We measured the release of the liver‐specific enzyme alanine aminotransferase (ALT) from the liver into the blood plasma of mice infected with the wild‐type strain SC5314, the heterozygous mutants and the null mutant ST13–63. The release of ALT from damaged liver cells upon invasion of the organ by hyphae is a useful parameter for candidal virulence, as described by Kretschmar and co‐workers (Kretschmar et al , 1999a;b). Compared with the highly virulent wild‐type strain SC5314, ALT levels measured in the blood of mice 24 h after inoculation were already significantly reduced in i.p.…”

“…Highly virulent strains of C. albicans , like SC5314 used here, are able to release high amounts of ALT in i.p. infections, probably by invading and penetrating liver cells (Kretschmar et al , 1999a;b). In contrast, infection with the mlt1 null mutant led to the release of lower ALT activity, which indicated less tissue damage in comparison with the wild‐type SC5314.…”

“…BALB/c mice were infected as described recently (Kretschmar et al. , 1999a) with C. albicans yeast cells with the following modifications using an inoculum of 1 × 10 8 .…”