Transcriptional regulation of autophagy, cell wall stress response and pathogenicity by Pho23 in C. albicans

The modification of chromatin by histone deacetylases (HDACs) has critical roles in transcriptional regulation. In this study, we identified the Rpd3 HDAC complex component Pho23 in Candida albicans and explored its role in the transcriptional regulation of physiological processes. PHO23 deletion increased autophagic activity and upregulated the transcription of ATG genes. Moreover, the deletion of PHO23 severely impaired cell wall stress resistance and reduced the cell wall integrity (CWI) pathway in response to cell wall stress. Furthermore, the pho23Δ/Δ mutant had partial defects in hyphal development and protease secretion, which were associated with the downregulation of genes involved in hyphal development (e.g. HWP1, ALS3 and ECE1) and genes encoding secreted aspartic proteases (e.g. SAP4, SAP5, SAP6 and SAP9). In addition, the deletion of PHO23 strongly attenuated systemic infection and kidney fungal burden in mice, demonstrating that Pho23 is required for the virulence of C. albicans. Together, our results revealed that Pho23 regulates many key physiological processes in C. albicans at the transcriptional level. These data also shed light on the potential for exploiting Rpd3 HDAC complex-related proteins as antifungal targets.