Genetic evidence for role of extracellular proteinase in virulence of Candida albicans.

The relationship between extracellular proteinase and the virulence for mice in Candida albicans was studied by using a set of three isolates. The set included a proteinase-producing parent (C9), a proteinase-deficient mutant derived from C9 by nitrous acid treatment (C9M1), and a spontaneous revertant (C9M1M) obtained by mouse passage of C9M1. The morphological markers and the carbon assimilation pattern were identical in these isolates. Isolate C9 produced a high level of proteinase in vitro and caused fatal infection (100%) within 21 days. The mutant produced no detectable enzymes in vitro, and all mice survived until day 22. Only 30% of the mice infected with C9M1 died between day 23 and 30. The isolates recovered from the dead mice were found to be proteinase sufficient, indicating that the mice died after the organism in tissue had reverted. The C9M1M isolate produced proteinase in vitro at 44% the level of C9 and induced fatal infection in 90% of the mice within 30 days. The number of CFU recovered from the kidneys correlated with the level of proteinase produced in vitro and, in turn, the rate of fatal infection produced by the isolates. These results support a previous observation indicating that proteinase activity is one of the virulence factors associated with C. albicans.