@article{f79a05b86f204b42b3cefb0845932fe9,
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 {\textquoteleft}Candidalysin{\textquoteright} for this cytolytic peptide toxin; a newly identified, critical molecular determinant of epithelial damage and host recognition of the clinically important fungus, C. albicans.",
keywords = "antimicrobial responses, fungal host response, fungal pathogenesis",
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 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 Wheeler, {Robert T} and Thomas Gutsmann and Bernhard Hube and Naglik, {Julian R.}",
note = "Acknowledgements We thank S. Gaffen, B. Klein, C. Hertweck, A. Tucker, J. Green and S. Challacombe for comments on the manuscript. For experimental assistance, we thank S. Bevan and D. Andersson (calcium assays), D. Nayar (histology), D. Rahman and M. Mistry (murine model), M. Nilan (zebrafish model), S. Groth (FRET spectroscopy), N. Gebauer (Impedance experiments), D. Schulz (kex1∆/∆ strain) and our colleagues for supplying fungal mutant strains. This work was supported by grants from the Medical Research Council (MR/J008303/1, MR/M011372/1), Biotechnology & Biological Sciences Research Council (BB/J015261/1), FP7-PEOPLE-2013-Initial Training Network (606786) to J.R.N.; Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z) to J.R.N. and D.W.; Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (102549/Z/13/Z) to D.W.; Deutsche Forschungsgemeinschaft CRC/TR124 FungiNet Project C1 and Z2, Deutsche Forschungsgemeinschaft SPP 1580 (Hu 528/17-1) and CSCC, German Federal Ministry of Education and Health (BMBF) 01EO1002 to B.Hu.; Cluster of Excellence {\textquoteleft}Inflammation at interfaces{\textquoteright} and Deutsche Forschungsgemeinschaft SPP1580 project GU 568/5-1 to T.G.; National Institutes of Health (R15AI094406) and the Burroughs Wellcome Fund to R.T.W",
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",
}