Candidalysin is a fungal peptide toxin critical for mucosal infection.

Moyes DL*, Wilson D*, Richardson JP*, Mogavero S*, Tang SX, Wernecke J, Höfs S, Gratacap RL, Robbins J, Runglall M, Murciano C, Blagojevic M, Thavaraj S, Förster TM, Hebecker B, Kasper L, Vizcay G, Iancu SI, Kichik N, Häder A, Kurzai O, Luo T, Krüger T, Kniemeyer O, Cota E, Bader O, Wheeler RT, Gutsmann T, Hube B, Naglik JR (2016) Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature 532(7597), 64-68.

*equal contribution

Abstract

* shared first authors

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. Such toxins have not been identified previously in human pathogenic fungi. Here we identify the first, to our knowledge, fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans. This secreted toxin directly damages epithelial membranes, triggers a danger response signalling pathway and activates epithelial immunity. Membrane permeabilization is enhanced by a positive charge at the carboxy terminus of the peptide, which 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.

Leibniz-HKI-Authors

Toni Förster
Antje Häder
Betty Hebecker
Sarah Höfs
Bernhard Hube
Lydia Kasper
Olaf Kniemeyer
Thomas Krüger
Oliver Kurzai
Ting Luo
Selene Mogavero

Awards

DGHM "Paper of the Months" April 2016; Recommended by Faculty 1000 as exaptional (4x); Comments in Nature and Nature Reviews Microbiology; Publication Award 2016 of the German Speaking Mycology Society; Medac Research Award 2016

Identifier

doi: 10.1038/nature17625

PMID: 27027296