Identification of Candidalysin : a Candida albicans peptide toxin involved in epithelial damage
Normally a harmless coloniser of the skin and mucosal surfaces, Candida albicans can cause serious disease. The morphological switch from a budding yeast to a hyphal growth form is considered as one of the most important virulence traits, as hyphae contribute to epithelial invasion and tissue damage. Yeast-to-hypha transition is accompanied by the expression of a variety of hypha-associated proteins, which strongly contribute to the virulent properties of hyphae. Such a protein is Ece1, whose expression is strictly correlated to the formation of hyphae. While mutants lacking ECE1 are still able to form proper hyphae, activation of the epithelial danger response pathways by these mutants is impaired, demonstrating that Ece1 may play an important role in C. albicans-mediated epithelial damage. The aim of this study was to elucidate the so far unknown function of this protein. Using a set of ece1Δ/Δ mutants, the importance of Ece1 for adherence to, invasion into and damage of epithelial cells was examined. Furthermore, the eight Ece1 peptides that were predicted to result from intracellular processing of the full length protein were examined for their damaging potential on epithelial cells and human erythrocytes. It was found that only one of the eight Ece1 peptides, i.e. peptide Ece1-III, was highly cytolytic on all cell types tested. This short peptide displayed pore-forming properties, resulting in the identification of this peptide as the first known peptide toxin of a human fungal pathogen. Due to the rapid and efficient lysis of host cells, the peptide was named “Candidalysin”. In summary, this study provides insight into the as yet unknown function and role of Ece1 in infection-associated epithelial damage and demonstrates the importance of the characterisation of all C. albicans ORFs for the identification of further fungal virulence factors.