Candidalysin is a fungal peptide toxin critical for mucosal infection

David L. Moyes, Duncan Wilson, Jonathan P. Richardson, Selene Mogavero, Shirley X. Tang, Julia Wernecke, Sarah Höfs, Remi L. Gratacap, Jon Robbins, Manohursingh Runglall, Celia Murciano, Mariana Blagojevic, Selvam Thavaraj, Toni M. Förster, Betty Hebecker, Lydia Kasper, Gema Vizcay, Simona I. Iancu, Nessim Kichik, Antje Häder, Oliver Kurzai, Ting Luo, Thomas Krüger, Olaf Kniemeyer, Ernesto Cota, Oliver Bader, Robert T. Wheeler, Thomas Gutsmann, Bernhard Hube () and Julian R. Naglik
Additional contact information
David L. Moyes: Dental Institute, King’s College London
Duncan Wilson: Hans Knöll Institute
Jonathan P. Richardson: Dental Institute, King’s College London
Selene Mogavero: Hans Knöll Institute
Shirley X. Tang: Dental Institute, King’s College London
Julia Wernecke: Research Center Borstel
Sarah Höfs: Hans Knöll Institute
Remi L. Gratacap: University of Maine
Jon Robbins: Wolfson CARD, King’s College London, Guy’s Campus
Manohursingh Runglall: Dental Institute, King’s College London
Celia Murciano: Dental Institute, King’s College London
Mariana Blagojevic: Dental Institute, King’s College London
Selvam Thavaraj: Dental Institute, King’s College London
Toni M. Förster: Hans Knöll Institute
Betty Hebecker: Hans Knöll Institute
Lydia Kasper: Hans Knöll Institute
Gema Vizcay: Centre for Ultrastructural Imaging, King’s College London
Simona I. Iancu: Dental Institute, King’s College London
Nessim Kichik: Dental Institute, King’s College London
Antje Häder: Septomics Research Center, Hans-Knöll Institute and Friedrich Schiller University
Oliver Kurzai: Septomics Research Center, Hans-Knöll Institute and Friedrich Schiller University
Ting Luo: Hans Knöll Institute
Thomas Krüger: Hans Knöll Institute
Olaf Kniemeyer: Hans Knöll Institute
Ernesto Cota: Imperial College London
Oliver Bader: Institute for Medical Microbiology, University Medical Center Göttingen
Robert T. Wheeler: University of Maine
Thomas Gutsmann: Research Center Borstel
Bernhard Hube: Hans Knöll Institute
Julian R. Naglik: Dental Institute, King’s College London

Nature, 2016, vol. 532, issue 7597, 64-68

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/nature17625

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