The importance of strain variation in virulence of Candida dubliniensis and Candida albicans: results of a blinded histopathological study of invasive candidiasis

The pathogenic yeast Candida dubliniensis is increasingly reported as a cause of systemic fungal infections. We compared the virulence of 9 clinical bloodstream isolates of C. dubliniensis with 3 C. albicans isolates in a murine model of invasive candidiasis. Quantification of organisms and inflammatory changes in kidneys of infected animals were evaluated in a blinded, systematic manner. Average 7-day mortality among animals infected with C. dubliniensis was 21.0% (33/157 animals; range for strains: 0–57.1%); and with C. albicans 23.2%, (23/99 animals; range for strains: 6.7–85.0%) (p 0.65). Greater strain variation was noted within species than between the two species. Both species comprised strains of either high or low virulence, and six of the nine C. dubliniensis strains showed negligible virulence. Colony counts determined on samples from liver and kidneys did not differ between species. According to histopathological analysis, C. dubliniensis produced significantly lower levels of hyphae than C. albicans (p <0.001). Candida albicans caused a greater inflammatory response in kidneys (p <0.001) and was more commonly associated with granulomatous inflammation (p 0.003) and greater mononuclear infiltrate (p <0.001). According to multivariate analysis, increasing tissue burden of both hyphal forms (p 0.032) and yeasts (p 0.016) was independently associated with death, whereas higher levels of mononuclear cells were protective (p <0.001). The results suggest a great overlap between the virulence properties of C. dubliniensis and C. albicans. Both yeast and hyphal forms are independently associated with mortality, suggesting similar virulence for both. The source of the fungal isolates may be a neglected confounding factor in virulence studies in animal models.