Comparative virulence of Candida albicans yeast and filamentous forms in orally and intravenously inoculated mice

Objective: Candida albicans, a dimorphic fungus that switches from yeast to filamentous forms, is a major cause of complicating systemic infection in intensive care patients. The aim of this study was to compare the pathogenic potential of C. albicans yeast and filamentous forms. Design: Separate groups of mice were inoculated either intravenously or orally with C. albicans CAF2 (wild type), HLC54 (yeast forms defective in filament formation), or BCa2-10 (constitutively filamentous). Mice were killed 1, 7, 14, and 21 days after intravenous C. albicans and kidneys and liver were quantitatively cultured; cohort groups were observed for mortality. Mice were pretreated with antibiotics for 3 days before oral inoculation with C. albicans, and killed 3 days later with dexamethasone administered for the latter 3 days; at sacrifice, the mesenteric lymph nodes and kidneys were cultured to monitor extraintestinal dissemination of C. albicans. Setting: University teaching hospital research laboratory. Subjects: Female, Swiss Webster, adult mice. Measurements and Main Results: In intravenously inoculated mice, mortality was highest with wild-type C. albicans CAF2 (92%), intermediate with HLC54 (56%), and not detected with constitutively filamentous BCa2-10 (0%); BCa2-10 was cleared from the kidney and liver, but CAF2 and HLC54 were recovered at approximately 10^5-7/g kidney and 10^4-5/g liver. There was only occasional mortality in orally inoculated mice and the numbers of cecal C. albicans CAF2 and HLC54 were similarly high (approximately 10⁷/g), whereas numbers of cecal BCa2-10 were at least 100-fold lower. Extraintestinal dissemination was greatest with HLC54, intermediate with CAF2, and undetectable with BCa2-10. Conclusions: Of the three C. albicans strains studied, wild-type CAF2 was most virulent in intravenously inoculated mice and HLC54 (defective in filament formation) was most virulent in orally inoculated mice. The constitutively filamentous BCa2-10 was avirulent in both models, suggesting that filamentous forms by themselves might not be critically important for C. albicans virulence.