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.
authors.affiliation: Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK.
authors.forename: David L
authors.initials: DL
authors.lastname: Moyes
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, D-07745 Jena, Germany.
authors.forename: Duncan
authors.initials: D
authors.lastname: Wilson
authors.affiliation: Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Richardson
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, D-07745 Jena, Germany.
authors.forename: Selene
authors.initials: S
authors.lastname: Mogavero
authors.affiliation: Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK.
authors.forename: Shirley X
authors.initials: SX
authors.lastname: Tang
authors.affiliation: Research Center Borstel, Division of Biophysics, D-23845 Borstel, Germany.|Deutsches Elektronen-Synchrotron DESY, D-22607 Hamburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Wernecke
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, D-07745 Jena, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Höfs
authors.affiliation: Department of Molecular &Biomedical Sciences, University of Maine, Orono, Maine 04469, USA.
authors.forename: Remi L
authors.initials: RL
authors.lastname: Gratacap
authors.affiliation: Wolfson CARD, King's College London, Guy's Campus, London SE1 1UL, UK.
authors.forename: Jon
authors.initials: J
authors.lastname: Robbins
authors.affiliation: Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK.
authors.forename: Manohursingh
authors.initials: M
authors.lastname: Runglall
authors.affiliation: Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK.
authors.forename: Celia
authors.initials: C
authors.lastname: Murciano
authors.affiliation: Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK.
authors.forename: Mariana
authors.initials: M
authors.lastname: Blagojevic
authors.affiliation: Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK.
authors.forename: Selvam
authors.initials: S
authors.lastname: Thavaraj
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, D-07745 Jena, Germany.
authors.forename: Toni M
authors.initials: TM
authors.lastname: Förster
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, D-07745 Jena, Germany.|Research Group Microbial Immunology, Hans Knöll Institute, D-07745 Jena, Germany.
authors.forename: Betty
authors.initials: B
authors.lastname: Hebecker
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, D-07745 Jena, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Kasper
authors.affiliation: Centre for Ultrastructural Imaging, King's College London, London SE1 1UL, UK.
authors.forename: Gema
authors.initials: G
authors.lastname: Vizcay
authors.affiliation: Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK.
authors.forename: Simona I
authors.initials: SI
authors.lastname: Iancu
authors.affiliation: Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK.|Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Nessim
authors.initials: N
authors.lastname: Kichik
authors.affiliation: Septomics Research Center, Hans-Knöll Institute and Friedrich Schiller University, D-07745 Jena, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Häder
authors.affiliation: Septomics Research Center, Hans-Knöll Institute and Friedrich Schiller University, D-07745 Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
authors.affiliation: Department of Molecular and Applied Microbiology, Hans Knöll Institute, D-07745 Jena, Germany.
authors.forename: Ting
authors.initials: T
authors.lastname: Luo
authors.affiliation: Department of Molecular and Applied Microbiology, Hans Knöll Institute, D-07745 Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krüger
authors.affiliation: Department of Molecular and Applied Microbiology, Hans Knöll Institute, D-07745 Jena, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Kniemeyer
authors.affiliation: Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Cota
authors.affiliation: Institute for Medical Microbiology, University Medical Center Göttingen, D-37075 Göttingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bader
authors.affiliation: Department of Molecular &Biomedical Sciences, University of Maine, Orono, Maine 04469, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Wheeler
authors.affiliation: Research Center Borstel, Division of Biophysics, D-23845 Borstel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gutsmann
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, D-07745 Jena, Germany.|Friedrich Schiller University, D-07737 Jena, Germany.|Integrated Research and Treatment Center, Center for Sepsis Control and Care, D-07747 Jena, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hube
authors.affiliation: Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Naglik
mesh_terms: D002118:Calcium / Q000378:metabolism; D002176:Candida albicans / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity*; D002177:Candidiasis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D002463:Cell Membrane Permeability / Q000187:drug effects; D003603:Cytotoxins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D009092:Mucous Membrane / Q000382:microbiology / Q000473:pathology; D009183:Mycotoxins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D014774:Virulence / Q000187:drug effects; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity
chemical_list: D003603:Cytotoxins; C082909:ECE1 protein, Candida albicans; D005656:Fungal Proteins; D009183:Mycotoxins; D037521:Virulence Factors; D002118:Calcium