Quantification of biophysical properties of candidalysin, a fungal peptide toxin secreted by C. albicans during invasion.

Abstract

Candida albicans fungus can cause invasive candidiasis. To become pathogenic and translocate across the intestinal epithelium C.abicans fungus needs to change its morphology from yeast to invasive filamentous. Virulence factor candidalysin secreted during fungal invasion, is found to be crucial in direct cell membrane damage, the stimulation of a danger response signalling pathway, and the activation of epithelial immunity. Due to its amphiphilic alpha-helical structure peptide has a high binding affinity to plasma membranes. With increasing accumulation on the membrane surfaces, the alpha-helix peptide starts penetration of the lipid bilayer until the plasma membrane is damaged. However, whether there is specific affinity to different membrane compositions is still unknown. Here we determined the concentrations of candidalysin required for membrane permeabilization of large unilamellar vesicles with various lipid compositions. Then, we used spectral imaging to assess the lipid packing changes in giant unilamellar vesicles of different lipid composition resembling human epithelial, bacterial and fungal membranes under the treatment of candidalysin. Solvatochromic polarity-sensitive dyes were used to label model membranes. Spectral imaging data allowed to calculate generalized polarization map of the labelled membrane and further investigate lipid packing during peptide binding.