is the primary etiological agent of vulvovaginal candidiasis (VVC) and exerts its pathogenicity through secretion of the peptide toxin candidalysin encoded by the ECE1 gene. A highly conserved variant ECE1 sequence exists across a diverse set of clinical isolates. Thus, we sought to determine the relative pathogenicity and mechanism(s) associated with this alternative ECE1 allele.


Isogenic strains harboring WT or variant ECE1 sequences were engineered in an Δ/Δece1 background. After confirmation of equivalent expression by qPCR, pathogenicity of strains were tested using in vitro epithelial cell and in vivo VVC models of infection and LDH, IL-1β, neutrophil levels monitored. Follow up studies using synthetic candidalysin peptide were also performed. Lastly, a panel of ECE1 chimeras were constructed to assess potential processing defects and detected by a novel HiBiT-tagging approach.


Strains transformed with either the variant full length ECE1 or candidalysin allele, as compared to the WT sequence, demonstrated significantly reduced immunopathogenicity during in vitro or in vivo infection despite equivalent fungal burden. Interestingly, epithelial challenge with WT or variant synthetic peptide revealed similar capacity to elicit damage and IL-1β. Allele profiling and ECE1 chimera experiments demonstrated that defects in pathogenicity are at least partly due to inefficient ECE1 processing at the peptide 2-peptide 3 junction.


The ECE1 gene displays conserved polymorphisms that alter candidalysin secretion and strain pathogenicity. Future work is focused on determining specific amino acid sequences that contribute to these affects across clinical isolates and disease states.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.

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