A conserved Sas10/C1D domain protein, CaLrp1, is a critical regulator of hyphal development and pathogenicity in...

Candida albicans represents the predominant opportunistic fungal pathogen in clinical contexts, with its virulence contingent upon multilayered regulatory networks. CaLrp1 (orf19.5067) encodes a conserved Sas10/C1D domain-containing protein, though its precise biological role has remained uncharacterized.

CaLrp1 deleted and complemented strains were constructed to systematically investigate its function in C. albicans. Abrogation of CaLrp1 resulted in delayed hyphal induction, a loss of rugose colony morphology, and a pronounced reduction in invasive growth on solid media. Furthermore, the mutant demonstrated impaired epithelial translocation, diminished capacity to damage Caco-2 cells, and enhanced susceptibility to macrophage phagocytosis in vitro. In murine models of gastrointestinal colonization and systemic infection, CaLrp1-deficient strains displayed restricted proliferative capacity, reduced tissue pathology, and significantly attenuated virulence. Transcriptomic profiling via RNA-seq revealed that CaLrp1 deletion induced extensive transcriptional reprogramming, marked by the downregulation of genes implicated in ribosome biogenesis, rRNA processing, energy metabolism, and multiple virulence-associated pathways. Notably, key hyphal development and adhesion genes-including Als1, Ece1, and Hwp1-were significantly suppressed, a finding consistent with the phenotypic defects observed on solid substrates.

Our results establish CaLrp1 as a critical regulator of C. albicans morphogenesis and pathogenicity, likely operating via the maintenance of cellular RNA-processing and protein-biosynthetic fidelity.