A new regulator in the crossroads of oxidative stress resistance and virulence in <i>Candida glabrata</i>: The transcription factor CgTog1

<i>Candida glabrata</i> is a prominent pathogenic yeast which exhibits a unique ability to survive the harsh environment of host immune cells. In this study, we describe the role of the transcription factor encoded by the gene <i>CAGL0F09229g</i>, here named CgTog1 after its <i>Saccharomyces cerevisiae</i> ortholog, as a new determinant of <i>C. glabrata</i> virulence. Interestingly, Tog1 is absent in the other clinically relevant <i>Candida</i> species (<i>C. albicans, C. parapsilosis, C. tropicalis, C. auris</i>), being exclusive to <i>C. glabrata</i>. CgTog1 was found to be required for oxidative stress resistance and for the modulation of reactive oxygen species inside <i>C. glabrata</i> cells. Also, CgTog1 was observed to be a nuclear protein, whose activity up-regulates the expression of 147 genes and represses 112 genes in <i>C. glabrata</i> cells exposed to H₂O₂, as revealed through RNA-seq-based transcriptomics analysis. Given the importance of oxidative stress response in the resistance to host immune cells, the effect of <i>CgTOG1</i> expression in yeast survival upon phagocytosis by <i>Galleria mellonella</i> hemocytes was evaluated, leading to the identification of CgTog1 as a determinant of yeast survival upon phagocytosis. Interestingly, CgTog1 targets include many whose expression changes in <i>C. glabrata</i> cells after engulfment by macrophages, including those involved in reprogrammed carbon metabolism, glyoxylate cycle and fatty acid degradation. In summary, CgTog1 is a new and specific regulator of virulence in <i>C. glabrata</i>, contributing to oxidative stress resistance and survival upon phagocytosis by host immune cells.