Journal
NATURE
Volume 532, Issue 7597, Pages 64-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature17625
Keywords
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Funding
- Medical Research Council [MR/J008303/1, MR/M011372/1]
- Biotechnology & Biological Sciences Research Council [BB/J015261/1]
- FP7-PEOPLE-Initial Training Network [606786]
- Wellcome Trust [097377/Z/11/Z, 102549/Z/13/Z]
- Royal Society [102549/Z/13/Z]
- Deutsche Forschungsgemeinschaft [CRC/TR124, SPP 1580 (Hu 528/17-1)]
- CSCC, German Federal Ministry of Education and Health (BMBF) [01E01002]
- Cluster of Excellence 'Inflammation at interfaces' and Deutsche Forschungsgemeinschaft [SPP1580, GU 568/5-1]
- National Institutes of Health [R15AI094406]
- Burroughs Wellcome Fund
- Wellcome Trust [102549/Z/13/Z] Funding Source: Wellcome Trust
- BBSRC [BB/K003887/1, BB/N014677/1] Funding Source: UKRI
- MRC [MR/M011372/1, MR/J008303/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/N014677/1, BB/K003887/1] Funding Source: researchfish
- Medical Research Council [MR/J008303/1, MR/M011372/1] Funding Source: researchfish
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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.
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