Format

Send to

Choose Destination
Nature. 2016 Apr 7;532(7597):64-8. doi: 10.1038/nature17625. Epub 2016 Mar 30.

Candidalysin is a fungal peptide toxin critical for mucosal infection.

Author information

1
Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK.
2
Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, D-07745 Jena, Germany.
3
Research Center Borstel, Division of Biophysics, D-23845 Borstel, Germany.
4
Deutsches Elektronen-Synchrotron DESY, D-22607 Hamburg, Germany.
5
Department of Molecular &Biomedical Sciences, University of Maine, Orono, Maine 04469, USA.
6
Wolfson CARD, King's College London, Guy's Campus, London SE1 1UL, UK.
7
Research Group Microbial Immunology, Hans Knöll Institute, D-07745 Jena, Germany.
8
Centre for Ultrastructural Imaging, King's College London, London SE1 1UL, UK.
9
Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
10
Septomics Research Center, Hans-Knöll Institute and Friedrich Schiller University, D-07745 Jena, Germany.
11
Department of Molecular and Applied Microbiology, Hans Knöll Institute, D-07745 Jena, Germany.
12
Institute for Medical Microbiology, University Medical Center Göttingen, D-37075 Göttingen, Germany.
13
Friedrich Schiller University, D-07737 Jena, Germany.
14
Integrated Research and Treatment Center, Center for Sepsis Control and Care, D-07747 Jena, Germany.

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.

PMID:
27027296
PMCID:
PMC4851236
DOI:
10.1038/nature17625
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Author Information Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests. Readers are welcome to comment on the online version of the paper. Correspondence and requests for materials should be addressed to BHu (bernhard.hube@leibniz-hki.de).

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center