Candida glabrata Transcription Factor Rpn4 Mediates Fluconazole Resistance through Regulation of Ergosterol Biosynthesis and Plasma Membrane Permeability.

ABSTRACT: The ability to acquire azole resistance is an emblematic trait of the fungal pathogen Candida glabrata Understanding the molecular basis of azole resistance in this pathogen is crucial for designing more suitable therapeutic strategies. This study shows that the C. glabrata transcription factor (TF) CgRpn4 is a determinant of azole drug resistance. RNA sequencing during fluconazole exposure revealed that CgRpn4 regulates the expression of 212 genes, activating 80 genes and repressing, likely in an indirect fashion, 132 genes. Targets comprise several proteasome and ergosterol biosynthesis genes, including ERG1, ERG2, ERG3, and ERG11 The localization of CgRpn4 to the nucleus increases upon fluconazole stress. Consistent with a role in ergosterol and

SUBMITTER: Pais P 

PROVIDER: S-EPMC7449212 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature