Abstract
Candida albicans is one of the most common causes of superficial and invasive fungal disease in humans. Its ability to cause disease has been closely linked to its ability to undergo a morphological transition from budding yeast to filamentous forms (hyphae and pseudohyphae). The ability of C. albicans strains isolated from patients to undergo filamentation varies significantly. In addition, the filamentation phenotypes of mutants involving transcription factors that positively regulate hyphal morphogenesis can also vary from strain to strain. Here, we characterized the virulence, in vitro and in vivo filamentation, and in vitro and in vivo hypha-associated gene expression profiles of four poorly filamenting C. albicans isolates and their corresponding deletion mutants of the repressor of filamentation NRG1. The two most virulent strains, 57055 and 78048, show robust in vivo filamentation while remaining predominately yeast phase exposed to RPMI+10% bovine calf serum at 37°C; the two low virulence strains (94015 and 78042) do not filament well under either condition. Deletion of NRG1 increases hyphae formation in the SC5314 derivative SN250 but only pseudohyphae are formed in the clinical isolates in vivo. Deletion of NRG1 modestly increased the virulence of 78042 which was accompanied by increased expression of hyphae-associated genes without an increase in filamentation. Strikingly, deletion of NRG1 in 78048 reduced filamentation, expression of candidalysin (ECE1) and virulence in vivo without dramatically altering establishment of infection. Thus, the function of NRG1 varies significantly within this set of C. albicans isolates and can actually suppress filamentation in vivo.