Publication Date:
2016-03-31
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851236/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851236/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moyes, David L -- Wilson, Duncan -- Richardson, Jonathan P -- Mogavero, Selene -- Tang, Shirley X -- Wernecke, Julia -- Hofs, Sarah -- Gratacap, Remi L -- Robbins, Jon -- Runglall, Manohursingh -- Murciano, Celia -- Blagojevic, Mariana -- Thavaraj, Selvam -- Forster, Toni M -- Hebecker, Betty -- Kasper, Lydia -- Vizcay, Gema -- Iancu, Simona I -- Kichik, Nessim -- Hader, Antje -- Kurzai, Oliver -- Luo, Ting -- Kruger, Thomas -- Kniemeyer, Olaf -- Cota, Ernesto -- Bader, Oliver -- Wheeler, Robert T -- Gutsmann, Thomas -- Hube, Bernhard -- Naglik, Julian R -- 097377/Z/11/Z/Wellcome Trust/United Kingdom -- 102549/Z/13/Z/Wellcome Trust/United Kingdom -- BB/J015261/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MR/J008303/1/Medical Research Council/United Kingdom -- MR/M011372/1/Medical Research Council/United Kingdom -- R15 AI094406/AI/NIAID NIH HHS/ -- R15AI094406/AI/NIAID NIH HHS/ -- England -- Nature. 2016 Apr 7;532(7597):64-8. doi: 10.1038/nature17625. Epub 2016 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK. ; Department of Microbial Pathogenicity Mechanisms, Hans Knoll Institute, D-07745 Jena, Germany. ; Research Center Borstel, Division of Biophysics, D-23845 Borstel, Germany. ; Deutsches Elektronen-Synchrotron DESY, D-22607 Hamburg, Germany. ; Department of Molecular &Biomedical Sciences, University of Maine, Orono, Maine 04469, USA. ; Wolfson CARD, King's College London, Guy's Campus, London SE1 1UL, UK. ; Research Group Microbial Immunology, Hans Knoll Institute, D-07745 Jena, Germany. ; Centre for Ultrastructural Imaging, King's College London, London SE1 1UL, UK. ; Department of Life Sciences, Imperial College London, London SW7 2AZ, UK. ; Septomics Research Center, Hans-Knoll Institute and Friedrich Schiller University, D-07745 Jena, Germany. ; Department of Molecular and Applied Microbiology, Hans Knoll Institute, D-07745 Jena, Germany. ; Institute for Medical Microbiology, University Medical Center Gottingen, D-37075 Gottingen, Germany. ; Friedrich Schiller University, D-07737 Jena, Germany. ; Integrated Research and Treatment Center, Center for Sepsis Control and Care, D-07747 Jena, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27027296" target="_blank"〉PubMed〈/a〉
Keywords:
Calcium/metabolism
;
Candida albicans/immunology/*metabolism/*pathogenicity
;
Candidiasis/metabolism/microbiology/pathology
;
Cell Membrane Permeability/drug effects
;
Cytotoxins/genetics/*metabolism/secretion/toxicity
;
Epithelial Cells/drug effects/immunology/pathology
;
Fungal Proteins/genetics/metabolism/secretion/*toxicity
;
Host-Pathogen Interactions/immunology
;
Humans
;
Mucous Membrane/microbiology/pathology
;
Mycotoxins/genetics/metabolism/secretion/*toxicity
;
Signal Transduction/drug effects
;
Virulence/drug effects
;
Virulence Factors/genetics/*metabolism/toxicity
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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