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Candidalysin is a fungal peptide toxin critical for mucosal infection

Author

Listed:
  • David L. Moyes

    (Dental Institute, King’s College London)

  • Duncan Wilson

    (Hans Knöll Institute
    Present addresses: Aberdeen Fungal Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK (D.W.); NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 1UL, UK (M.R.); ERI Biotecmed & Microbiology and Ecology Department, University of Valencia, Valencia 46100, Spain (C.M.).)

  • 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
    Deutsches Elektronen-Synchrotron DESY)

  • 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
    Present addresses: Aberdeen Fungal Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK (D.W.); NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 1UL, UK (M.R.); ERI Biotecmed & Microbiology and Ecology Department, University of Valencia, Valencia 46100, Spain (C.M.).)

  • Celia Murciano

    (Dental Institute, King’s College London
    Present addresses: Aberdeen Fungal Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK (D.W.); NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 1UL, UK (M.R.); ERI Biotecmed & Microbiology and Ecology Department, University of Valencia, Valencia 46100, Spain (C.M.).)

  • 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
    Research Group Microbial Immunology, 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
    Imperial 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
    Friedrich Schiller University
    Integrated Research and Treatment Center, Center for Sepsis Control and Care)

  • Julian R. Naglik

    (Dental Institute, King’s College London)

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.

Suggested Citation

  • 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 & Ma, 2016. "Candidalysin is a fungal peptide toxin critical for mucosal infection," Nature, Nature, vol. 532(7597), pages 64-68, April.
    • Handle: RePEc:nat:nature:v:532:y:2016:i:7597:d:10.1038_nature17625
    DOI: 10.1038/nature17625
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    Cited by:

    1. Tingting Zhou & Norma V. Solis & Michaela Marshall & Qing Yao & Rachel Garleb & Mengli Yang & Eric Pearlman & Scott G. Filler & Haoping Liu, 2024. "Hyphal Als proteins act as CR3 ligands to promote immune responses against Candida albicans," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Xionghui Ding & Hiroto Kambara & Rongxia Guo & Apurva Kanneganti & Maikel Acosta-Zaldívar & Jiajia Li & Fei Liu & Ting Bei & Wanjun Qi & Xuemei Xie & Wenli Han & Ningning Liu & Cunling Zhang & Xiaoyu , 2021. "Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    3. Joy Lachat & Alice Pascault & Delphine Thibaut & Rémi Borgne & Jean-Marc Verbavatz & Allon Weiner, 2022. "Trans-cellular tunnels induced by the fungal pathogen Candida albicans facilitate invasion through successive epithelial cells without host damage," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Melissa R. Cruz & Shane Cristy & Shantanu Guha & Giuseppe Buda Cesare & Elena Evdokimova & Hiram Sanchez & Dominika Borek & Pedro Miramón & Junko Yano & Paul L. Fidel & Alexei Savchenko & David R. And, 2022. "Structural and functional analysis of EntV reveals a 12 amino acid fragment protective against fungal infections," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Yu Liu & Ruina Wang & Jiacun Liu & Mengting Fan & Zi Ye & Yumeng Hao & Fei Xie & Ting Wang & Yuanying Jiang & Ningning Liu & Xiaoyan Cui & Quanzhen Lv & Lan Yan, 2024. "The vacuolar fusion regulated by HOPS complex promotes hyphal initiation and penetration in Candida albicans," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    6. Dandan Yang & Mao Zhang & Chang Su & Bin Dong & Yang Lu, 2023. "Candida albicans exploits N-acetylglucosamine as a gut signal to establish the balance between commensalism and pathogenesis," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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