Transcriptome analysis unveils Gln3 role in amino acids assimilation and fluconazole resistance in Candida glabrata.

After Candida albicans, Candidaglabrata is one the most common fungal species associated with candidemia in nosocomial infections. Rapid acquisition of nutrients from the host is important for pathogen survival, which possess metabolic flexibility to assimilate different carbon and nitrogen compounds. In Saccharomyces cerevisiae, nitrogen assimilation is controlled through a mechanism known as Nitrogen Catabolite Repression (NCR). NCR is coordinated by the action of four GATA factors; two positive regulators, Gat1 and Gln3, and two negative regulators, Gzf3 and Dal80. A similar mechanism to S. cerevisiae NCR, has not been broadly studied in C. glabrata. Previously, we have shown that in C. glabrata Gln3, but not Gat1, has a major role in nitrogen assimilation as opposed to what has been observed in S. cerevisiae in which both factors regulate NCR-sensitive genes. Here, we expand the knowledge about the role of Gln3 from C. glabrata through the transcriptional analysis of BG14 and gln3Δ strains. Approximately, 53.5% of the detected genes were differentially expressed (DEG). From these DEG, amino acid metabolism and ABC transporters were two of the most enriched KEGG categories in our analysis (Up-DEG and Down-DEG, respectively). Furthermore, a positive role of Gln3 in AAA assimilation was described, as well as its role in the transcriptional regulation of ARO8. Finally, an unexpected negative role for Gln3 in gene regulation of ABC transporters, CDR1, CDR2, and its associated transcriptional regulator PDR1 was found. This observation was confirmed by a decreased susceptibility of the gln3Δ strain to fluconazole.