Skn7p is involved in oxidative stress response and virulence of Candida glabrata

Candida glabrata is an opportunistic fungal pathogen that causes both superficial and deep-seated mycosis in humans. In Saccharomyces cerevisiae and several pathogenic fungi, Skn7p is known as a transcriptional factor involved in oxidative stress response (OSR) but functions of its ortholog have been little investigated in C. glabrata. In this study, we constructed a C. glabrata skn7 deletion strain by the ura-blaster technique and investigated mutant phenotypes related to OSR and virulence. The C. glabrata skn7 deletant showed increased susceptibility to hydrogen peroxide and tert-butyl hydroperoxide. Our transcriptional assay evaluated by quantitative real-time PCR revealed that, in response to the treatment with hydrogen peroxide, transcription of some putative Skn7p target genes including TRX2, TRR1, TSA1 and CTA1 were not fully induced in the skn7 deletant compared to the wild-type control, consistent with the susceptibility phenotype. Furthermore, the deletion of SKN7 resulted in attenuated virulence in a murine model of disseminated candidiasis. These results suggest that Skn7p may play a role in transcriptional regulation of its target genes required for OSR and virulence in C. glabrata.