Systematic functional profiling of WD40 proteins reveals Wcp1, a cyclophilin that links CO2/heat tolerance to acidic pH adaptation in Cryptococcus neoformans [RNA-Seq]

ABSTRACT: WD40 domains are major protein–protein interaction (PPI) scaffolds, yet their contributions to fungal pathogenicity remain poorly defined. We systematically analysed 94 canonical WD40 proteins in Cryptococcus neoformans. Conditional expression and sporulation analyses identified 36 essential WD40 proteins, while in vitro and in vivo profiling of 103 signature-tagged deletion strains spanning 52 genes uncovered 31 pathogenicity-related WD40 proteins, including epigenetic and post-transcriptional regulators. We highlighted Wcp1, a WD40–cyclophilin fusion required for growth at 37 °C under 5% CO₂. Both modules supported CO₂/heat tolerance and virulence. Notably, Wcp1 couples these functions to acidic pH adaptation: wcp1Δ mutants failed to grow under elevated temperature and CO₂ at acidic pH, exhibited enhanced intracellular acidification, reduced survival within macrophages and attenuated virulence in both Drosophila and murine models. Integrated transcriptomic and proteomic analyses revealed that Wcp1 acts as a central integrator of intracellular pH homeostasis by coordinating proton transport, metabolic adaptation and stress-buffering networks.

ORGANISM(S): Cryptococcus neoformans

PROVIDER: GSE328123 | GEO | 2026/05/16

REPOSITORIES: GEO