Structural Changes in Lipid Model Membranes Induced by the Fungal Peptide Toxin Ece1-III

Abstract

Ece1-III is the first peptide toxin identified in a human pathogenic fungus. This peptide consists of 32 amino acids and it is processed from the protein, Ece1p, which is exclusively expressed by the invasive hyphal form of the opportunistic fungus Candida albicans. The peptide of our interest triggers the host danger response pathway and activates epithelial immunity at low concentrations and shows a pronounced cytolytic effect on epithelial membranes with increasing concentration.We propose that Ece1-III partitions directly into the lipid matrix of biological cell membranes. The association with the membrane leads to its permeabilization and disintegration by one of three different pore-forming mechanisms: (i) the ‘barrel-stave model’, (ii) the ‘toroidal-pore model’, or (iii) the ‘detergent-like carpet model’. We suggest that the membrane perturbation is mainly driven by its characteristic amphipathic α-helical secondary structure and electrostatic interactions play only a minor role as the peptide exhibits a comparably low cationic net charge. Our aim is to reveal the interactions of the peptide with phospholipid model membranes either by assigning it to one of the models described so far or to evolve a new one. The understanding of the interaction mechanisms is of crucial importance with view to a potential protection of the integrity of human epithelial cell membranes and epithelial immunity.Here, we will present results of different biophysical techniques that characterize the lipid-peptide interaction. We will show that the peptide activity towards membranes containing the fungal lipid component ergosterol is reduced as compared to membranes with cholesterol which indicates that ergosterol adapts a self-protective function in C. albicans.