Moyes David L, Wilson Duncan, Richardson Jonathan P, Mogavero Selene, Tang Shirley X, Wernecke Julia, Höfs Sarah, Gratacap Remi L, Robbins Jon, Runglall Manohursingh, Murciano Celia, Blagojevic Mariana, Thavaraj Selvam, Förster Toni M, Hebecker Betty, Kasper Lydia, Vizcay Gema, Iancu Simona I, Kichik Nessim, Häder Antje, Kurzai Oliver, Luo Ting, Krüger Thomas, Kniemeyer Olaf, Cota Ernesto, Bader Oliver, Wheeler Robert T, Gutsmann Thomas, Hube Bernhard, Naglik Julian R
Mucosal &Salivary Biology Division, Dental Institute, King's College London SE1 1UL, UK.
Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, D-07745 Jena, Germany.
Nature. 2016 Apr 7;532(7597):64-8. doi: 10.1038/nature17625. Epub 2016 Mar 30.
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.
溶细胞蛋白和肽毒素是几种细菌病原体的经典毒力因子，它们会破坏上皮屏障功能、损伤细胞并激活或调节宿主免疫反应。此前在人类致病真菌中尚未发现此类毒素。在此，据我们所知，我们在机会性病原体白色念珠菌中首次鉴定出真菌溶细胞肽毒素。这种分泌型毒素直接损伤上皮细胞膜，触发危险反应信号通路并激活上皮免疫。肽的羧基末端的正电荷增强了膜通透性，这会触发伴随钙内流的内向电流。缺乏这种毒素的白色念珠菌菌株不会激活或损伤上皮细胞，并且在黏膜感染的动物模型中无毒力。我们为这种溶细胞肽毒素提议命名为“念珠菌溶素”；它是一种新发现的、对上皮损伤和临床上重要的真菌白色念珠菌的宿主识别起关键作用的分子决定因素。
