Project description:To elucidate role of IRE1 in Candida albicans, genome wide expressional profile change was compared by microarray analysis between wild type (SC5314) and IRE1 mutant (ire1 DX) cells after successful RNA extraction. Expression of six genes (HWP1, ECE1, SOD3, AMS1, YWP1, SIT1 and FET34) was validated by qPCR and observed to have similar expression pattern when compared to their relative expression in microaaray data.
Project description:The pathogenic yeast Candida albicans relies on morphogenesis—the transition from spherical yeast to filamentous hyphal forms—for infection. While morphogenesis requires Ire1, a transmembrane protein that canonically initiates the Unfolded Protein Response (UPR) through HAC1 mRNA splicing, the specific mechanisms linking Ire1 to filamentation remain unclear. Using transcriptome analysis, we found that the Ire1-dependent transcriptional response driving morphogenesis is fundamentally distinct from the canonical UPR response to proteotoxic stress, with minimal overlap between programs. Morphogenesis is associated with only limited HAC1 splicing compared to robust splicing during proteotoxic stress, and HAC1 deletion only partially impairs filamentation, unlike the near-complete loss observed with IRE1 deletion. These findings establish that Ire1 regulates hyphal development through previously uncharacterized HAC1-independent pathways. We identify cell wall integrity as a key HAC1-independent mechanism, with Ire1—but not Hac1—essential for cell wall stress tolerance and upregulation of cell wall biosynthesis genes during filamentation. Our data also reveal Ire1-dependent decreases in transcripts encoding secretory proteins during both proteotoxic stress and morphogenesis, consistent with a possible role for Ire1-mediated mRNA degradation in these processes. Given Ire1’s essential role in pathogenesis and extensive development of Ire1-targeting compounds for mammalian systems, our findings position Ire1 as a highly promising druggable target for novel antifungal therapeutics and development of fungal-specific inhibitors.
Project description:Goal: We employed RNA-seq to identify targets of regulation of the Candida albicans transcription regulator CUP9. The cup9 deletion mutant strain displays increased fitness in a mouse model of oropharyngeal candidiasis.
Project description:To elucidate the impact of IFU5 in Candida albicans, genome wide transcription profiling was performed in ifu5?/? mutant strain. Wild type and mutant cells were grown for 5 hours and RNA extracted from these cultures, followed by microarray profiling. Expression of six genes (EFG1, ALS3, SOD3, BMT4, COX2, NAD1) was validated by qPCR.