Rapid proliferation due to better metabolic adaptation results in full virulence of a filament-deficient Candida albicans strain

Abstract The ability of the fungal pathogen Candida albicans to undergo a yeast-to-hypha transition is believed be key virulence factor, as filaments mediate tissue damage. Here, we show that not necessarily reduced in filament-deficient strains, and results depend on infection model used. We generate strain by deletion or repression EED1 (known required for maintenance hyphal growth). Consistent with previous studies, attenuated damaging epithelial cells macrophages vitro mouse intraperitoneal infection. However, systemic infection, virulent wild type when mice are challenged intermediate infectious doses, even more using low doses. Retained associated rapid yeast proliferation, likely result metabolic adaptation improved fitness, leading high organ loads. Analyses cytokine responses vivo, well infections immunosuppressed mice, suggest differences immunopathology contribute some extent retained mutant. Our findings challenge long-standing hypothesis hyphae essential pathogenesis candidiasis C. .