Candida glabrata STE12 is required for wild-type levels of virulence and nitrogen starvation induced filamentation

The highly conserved fungal Ste12 transcription factor family of proteins play critical roles in the regulation of many cellular processes including mating, cell wall biosynthesis, filamentation and invasive growth. They are also important mediators of fungal virulence. The Candida glabrata STE12 homologue was cloned. The encoded protein has a single DNA binding homeodomain but lacks both a C2H2 zinc finger DNA binding domain and an apparent Dig1/Dig2 regulatory motif. Candida glabrata STE12 can functionally complement the nitrogen starvation induced filamentation and mating defects of Saccharomyces cerevisiae ste12 mutants. We also show that C. glabrata STE12 is required for nitrogen starvation-induced filamentation as ste12 mutants rarely produce pseudohyphae on nitrogen depleted media. Finally we describe a novel murine model of C. glabrata systemic disease and use this to demonstrate that C. glabrata ste12 mutants, although still able to cause disease, are attenuated for virulence compared with STE12 reconstituted strains. Candida glabrata STE12 is therefore the first virulence factor encoding gene to be described in this increasingly important fungal pathogen.