Halder, V. | bioRxiv Science

bioRxiv2025

Distinct Ire1-driven transcriptional responses control morphogenesis in Candida albicans

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. Remarkably, morphogenesis occurs without detectable HAC1 splicing, and HAC1 deletion only partially impairs filamentation, unlike complete loss with IRE1 deletion. These findings establish that Ire1 regulates hyphal development through previously uncharacterized HAC1-independent pathways. Our data reveal decreased transcription of secretory proteins in an Ire1-dependent manner, providing compelling evidence that C. albicans possesses regulated Ire1-dependent decay (RIDD) activity--a post-transcriptional mechanism not previously characterized in this pathogen. Additionally, 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. Given Ire1s 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.

cell biology↗

bioRxiv2019

Inhibition of jasmonate-mediated plant defences by the fungal metabolite higginsianin B

Infection of Arabidopsis thaliana by the ascomycete fungus Colletotrichum higginsianum is characterised by an early symptomless biotrophic phase followed by a destructive necrotrophic phase. The fungal genome contains 77 secondary metabolism-related biosynthetic gene clusters (BGCs), and their expression during the infection process is tightly regulated. Deleting CclA, a chromatin regulator involved in repression of some BGCs through H3K4 trimethylation, allowed overproduction of 3 families of terpenoids and isolation of 12 different molecules. These natural products were tested in combination with methyl jasmonate (MeJA), an elicitor of jasmonate responses, for their capacity to alter defence gene induction in Arabidopsis. Higginsianin B inhibited MeJA-triggered expression of the defence reporter VSP1p:GUS, suggesting it may block bioactive JA-Ile synthesis or signalling in planta. Using the JA-Ile sensor Jas9-VENUS, we found that higginsianin B, but not three other structurally-related molecules, suppressed JA-Ile signalling by preventing degradation of JAZ proteins, the repressors of JA responses. Higginsianin B likely blocks the 26S proteasome-dependent degradation of JAZ proteins because it inhibited chymotrypsin- and caspase-like protease activities. The inhibition of target degradation by higginsianin B also extended to auxin signalling, as higginsianin B treatment reduced IAA-dependent expression of DR5p:GUS. Overall, our data indicate that specific fungal secondary metabolites can act similarly to protein effectors to subvert plant immune and developmental responses.\n\nHighlightA diterpene secondary metabolite produced by a fungal pathogen suppresses plant jasmonate defense signalling by preventing the proteasomal degradation of JAZ repressor proteins.

plant biology↗