Temporal events in the intravenous challenge model for experimental Candida albicans infections in female mice

Abstract

We characterized the intravenous (i.v.) challenge model for disseminated Candida albicans infection in female BALB/c and DBA/2 mice. Clearance of fungi from the bloodstream and appearance of fungi in tissues were measured at intervals after challenge with various doses of C. albicans. The wild-type isolate SC5314 and derived strains CAF2–1 and CAI-4 transformed with CIp10 were of equal virulence in the model. Variability in mouse survival times, kidney fungal burdens and cachexia was lowest when challenge inocula were within the range 10⁴–10⁵ CFU g⁻¹ body weight in BALB/c mice, but brain fungal burdens and outcomes in DBA/2 mice were variable for all inocula tested. Critical times in the development of infections in optimally challenged BALB/c mice were at 5–10 h (bloodstream fully cleared of fungi), 24 h (start of exponential fungal growth in kidneys) and 48 h (50% of blood cultures become positive). Differential involvement of right and left kidneys occurred almost exclusively in mice challenged with 4 CFU g⁻¹. We conclude that the i.v. challenge model in female BALB/c mice is now sufficiently well characterized to permit more refined experimentation in future virulence studies with C. albicans mutants.