Tec1 and Ste12 transcription factors play a role in adaptation to low pH stress and biofilm formation in the human opportunistic fungal pathogen Candida glabrata

Eukaryotic cells respond to environmental cues through mitogen activated protein kinase (MAPK) signaling pathways. Each MAPK cascade is specific to particular stimuli and mediates specialized responses through activation of transcription factors. In the budding yeast, Saccharomyces cerevisiae, the pheromone-induced mating pathway and the starvation-responsive invasive growth/filamentation pathway generate their distinct outputs through the transcription factors Ste12 and Tec1, respectively. In this study, we report the functional characterization of these transcription factors in the closely related human opportunistic pathogenic yeast Candida glabrata. Two homologues each for S. cerevisiae TEC1 and STE12 were identified in C. glabrata. Both C. glabrata Tec1 proteins contain the N-terminal TEA DNA-binding domain characteristic of the TEA/ATTS transcription factor family. Similarly, the DNA-binding homeodomain shared by members of the highly conserved fungal Ste12 transcription factor family is present in N-terminus of both C. glabrata Ste12 transcription factors. We show that both C. glabrata STE12 genes are at least partial functional orthologues of S. cerevisiae STE12 as they can rescue the mating defect of haploid S. cerevisiae ste12 null mutant. Knockout of one of the STE12 genes (ORF CAGL0H02145g) leads to decreased biofilm development; a stronger biofilm-impaired phenotype results from loss of both CgSTE12 genes in the double deletion mutant (Cgste12ΔΔ). The transcript levels of one of the TEC1 genes (ORF CAGL0M01716g) were found to be upregulated upon exposure to low pH; its deletion causes slightly increased sensitivity to higher concentrations of acetic acid. Heat shock leads to increase in mRNA levels of one of the STE12 genes (ORF CAGL0M01254g). These findings suggest a role of Tec1 and Ste12 transcription factors in the regulation of some traits (biofilm formation, response to low pH stress and elevated temperature) that contribute to C. glabrata's ability to colonize various host niches and to occasionally cause disease.