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 Hofs, Remi L Gratacap, Jon Robbins, Manohursingh Runglall, Celia Murciano, Mariana Blagojevic, Selvam Thavaraj, Toni M Forster, Betty Hebecker, Lydia Kasper, Gema Vizcay, Simona I Iancu, Nessim Kichik, Antje HaderOliver Kurzai, Ting Luo, Thomas Kruger, Olaf Kniemeyer, Ernesto Cota, Oliver Bader, Robert T Wheeler, Thomas Gutsmann, Bernhard Hube, Julian R. Naglik

Research output: Contribution to journalArticle

261 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)64-68
Number of pages5
JournalNature
Volume532
Issue number7597
Early online date30 Mar 2016
DOIs
Publication statusPublished - 7 Apr 2016

Keywords

  • antimicrobial responses
  • fungal host response
  • fungal pathogenesis

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    Moyes, D. L., Wilson, D., Richardson, J. P., Mogavero, S., Tang, S. X., Wernecke, J., Hofs, S., Gratacap, R. L., Robbins, J., Runglall, M., Murciano, C., Blagojevic, M., Thavaraj, S., Forster, T. M., Hebecker, B., Kasper, L., Vizcay, G., Iancu, S. I., Kichik, N., ... Naglik, J. R. (2016). Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature, 532(7597), 64-68. https://doi.org/10.1038/nature17625