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-Barrena; Simona I. Iancu; Nessim Kichik; Antje Hader; Oliver Kurzai; Ting Luo; Thomas Kruger; Olaf Kniemeyer; Ernesto  Cota; Oliver Bader; Oliver Bader; Robert T Wheeler; Thomas Gutsmann; Bernhard Hube; Julian R. Naglik

doi:10.1038/nature17625

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-Barrena
, Simona I. Iancu
, Nessim Kichik
, Antje Hader

Oliver Kurzai, Ting Luo, Thomas Kruger, Olaf Kniemeyer, Ernesto Cota, Oliver Bader, Oliver Bader, Robert T Wheeler, Thomas Gutsmann, Bernhard Hube, Julian R. Naglik

Hans Knoll Institute
Research Center Borstel, Division of Biophysics, D-23845 Borstel, Germany.
DESY - Deutsches Elektronen-Synchrotron
Department of Molecular & Biomedical Sciences, University of Maine, Orono, Maine 04469, USA
Imperial College London
University Medical Center Göttingen
Friedrich Schiller University Jena
Integrated Research and Treatment Center, Center for Sepsis Control and Care, D-07747 Jena, Germany
King's College London

Research output: Contribution to journal › Article › peer-review

789 Citations (Scopus)

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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 language	English
Pages (from-to)	64-68
Number of pages	5
Journal	NATURE
Volume	532
Issue number	7597
Early online date	30 Mar 2016
DOIs	https://doi.org/10.1038/nature17625
Publication status	Published - 7 Apr 2016

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10.1038/nature17625

Candidalysin is a fungal peptide_MOYES_Accepted26February2016_GREEN AAMAccepted author manuscript, 21.3 MB

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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-Barrena, 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

@article{d1dabc5ee4e041f6ba06fb4d1f418b27,

title = "Candidalysin is a fungal peptide toxin critical for mucosal infection",

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.",

author = "Moyes, \{David L.\} and Duncan Wilson and Richardson, \{Jonathan P.\} and Selene Mogavero and Tang, \{Shirley X.\} and Julia Wernecke and Sarah Hofs and Gratacap, \{Remi L\} and Jon Robbins and Manohursingh Runglall and Celia Murciano and Mariana Blagojevic and Selvam Thavaraj and Forster, \{Toni M\} and Betty Hebecker and Lydia Kasper and Gema Vizcay-Barrena and Iancu, \{Simona I.\} and Nessim Kichik and Antje Hader and Oliver Kurzai and Ting Luo and Thomas Kruger and Olaf Kniemeyer and Ernesto Cota and Oliver Bader and Oliver Bader and Wheeler, \{Robert T\} and Thomas Gutsmann and Bernhard Hube and Naglik, \{Julian R.\}",

year = "2016",

month = apr,

day = "7",

doi = "10.1038/nature17625",

language = "English",

volume = "532",

pages = "64--68",

journal = "NATURE",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7597",

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Moyes, DL, Wilson, D, Richardson, JP, Mogavero, S, Tang, SX, Wernecke, J, Hofs, S, Gratacap, RL, Robbins, J , Runglall, M, Murciano, C, Blagojevic, M , Thavaraj, S, Forster, TM, Hebecker, B, Kasper, L, Vizcay-Barrena, G, Iancu, SI , Kichik, N, Hader, A, Kurzai, O, Luo, T, Kruger, T, Kniemeyer, O, Cota, E, Bader, O, Bader, O, Wheeler, RT, Gutsmann, T, Hube, B & Naglik, JR 2016, 'Candidalysin is a fungal peptide toxin critical for mucosal infection', NATURE, vol. 532, no. 7597, pp. 64-68. https://doi.org/10.1038/nature17625

TY - JOUR

T1 - Candidalysin is a fungal peptide toxin critical for mucosal infection

AU - Moyes, David L.

AU - Wilson, Duncan

AU - Richardson, Jonathan P.

AU - Mogavero, Selene

AU - Tang, Shirley X.

AU - Wernecke, Julia

AU - Hofs, Sarah

AU - Gratacap, Remi L

AU - Robbins, Jon

AU - Runglall, Manohursingh

AU - Murciano, Celia

AU - Blagojevic, Mariana

AU - Thavaraj, Selvam

AU - Forster, Toni M

AU - Hebecker, Betty

AU - Kasper, Lydia

AU - Vizcay-Barrena, Gema

AU - Iancu, Simona I.

AU - Kichik, Nessim

AU - Hader, Antje

AU - Kurzai, Oliver

AU - Luo, Ting

AU - Kruger, Thomas

AU - Kniemeyer, Olaf

AU - Cota, Ernesto

AU - Bader, Oliver

AU - Wheeler, Robert T

AU - Gutsmann, Thomas

AU - Hube, Bernhard

AU - Naglik, Julian R.

PY - 2016/4/7

Y1 - 2016/4/7

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84963537211

U2 - 10.1038/nature17625

DO - 10.1038/nature17625

M3 - Article

C2 - 27027296

SN - 0028-0836

VL - 532

SP - 64

EP - 68

JO - NATURE

JF - NATURE

IS - 7597

ER -

Candidalysin is a fungal peptide toxin critical for mucosal infection

Abstract

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