Candidalysin is a fungal peptide toxin critical for mucosal infection.
Candidalysin is a fungal peptide toxin critical for mucosal infection.
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DOI：
10.1038/nature17625
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发表时间：
2016-04-07
期刊：
影响因子：
64.8
通讯作者：
Naglik JR
中科院分区：
文献类型：
--
作者：
Moyes DL;Wilson D;Richardson JP;Mogavero S;Tang SX;Wernecke J;Höfs S;Gratacap RL;Robbins J;Runglall M;Murciano C;Blagojevic M;Thavaraj S;Förster TM;Hebecker B;Kasper L;Vizcay G;Iancu SI;Kichik N;Häder A;Kurzai O;Luo T;Krüger T;Kniemeyer O;Cota E;Bader O;Wheeler RT;Gutsmann T;Hube B;Naglik JR
细胞溶解蛋白和肽毒素是几种细菌病原体的经典毒力因子，它们破坏上皮屏障功能，损伤细胞并激活或调节宿主免疫反应。直到现在，人们还不知道人类致病真菌是否含有这种毒素。在这里，我们确定了第一个真菌细胞溶解肽毒素在机会致病菌白色念珠菌。这种分泌的毒素直接破坏上皮膜，触发危险反应信号通路，激活上皮免疫。带正电的c端增强了毒素介导的膜通透性，并引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，并且在粘膜感染的动物模型中是无毒的。我们建议将这种细胞溶解肽毒素命名为“念珠菌素”；一个新发现的关键分子决定上皮损伤和宿主识别临床重要真菌，白色念珠菌。
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. Until now human pathogenic fungi were not known to possess such toxins. Here we identify the first fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans. This secreted toxin directly damages epithelial membranes, triggers a danger response signaling pathway and activates epithelial immunity. Toxin-mediated membrane permeabilization is enhanced by a positively charged C-terminus and 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.