David L. Moyes 1 , Duncan Wilson 2 , Jonathan P. Richardson 1 , Selene Mogavero 2 , Shirley X. Tang 1 , Julia Wernecke 3 , 4 , Sarah Höfs 2 , Remi L. Gratacap 5 , Jon Robbins 6 , Manohursingh Runglall 1 , Celia Murciano 1 , Mariana Blagojevic 1 , Selvam Thavaraj 1 , Toni M. Förster 2 , Betty Hebecker 2 , 7 , Lydia Kasper 2 , Gema Vizcay 8 , Simona I. Iancu 1 , Nessim Kichik 1 , 9 , Antje Häder 10 , Oliver Kurzai 10 , Ting Luo 11 , Thomas Krüger 11 , Olaf Kniemeyer 11 , Ernesto Cota 9 , Oliver Bader 12 , Robert T. Wheeler 5 , Thomas Gutsmann 3 , Bernhard Hube 2 , 13 , 14 , Julian R. Naglik 1
30 March 2016
Cytolytic proteins and peptide toxins are classical virulence factors of several bacterial pathogens which disrupt epithelial barrier function, damage cells and activate or modulate host immune responses. Until now human pathogenic fungi were not known to possess such toxins. Here we identify the first fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans. This secreted toxin directly damages epithelial membranes, triggers a danger response signaling pathway and activates epithelial immunity. Toxin-mediated membrane permeabilization is enhanced by a positively charged C-terminus and triggers an inward current concomitant with calcium influx. C. albicans strains lacking this toxin do not activate or damage epithelial cells and are avirulent in animal models of mucosal infection. We propose the name ‘Candidalysin’ for this cytolytic peptide toxin; a newly identified, critical molecular determinant of epithelial damage and host recognition of the clinically important fungus, C. albicans.