Candidalysin is a fungal peptide toxin critical for mucosal infection

被引：645

作者：

Moyes, David L. ^{[1
]}

Wilson, Duncan ^{[2
,16
]}

Richardson, Jonathan P. ^{[1
]}

Mogavero, Selene ^{[2
]}

Tang, Shirley X. ^{[1
]}

Wernecke, Julia ^{[3
,4
]}

Hoefs, Sarah ^{[2
]}

Gratacap, Remi L. ^{[5
]}

Robbins, Jon ^{[6
]}

Runglall, Manohursingh ^{[1
,17
]}

Murciano, Celia ^{[1
,18
]}

Blagojevic, Mariana ^{[1
]}

Thavaraj, Selvam ^{[1
]}

Foerster, Toni M. ^{[2
]}

Hebecker, Betty ^{[2
,7
]}

Kasper, Lydia ^{[2
]}

Vizcay, Gema ^{[8
]}

Iancu, Simona I. ^{[1
]}

Kichik, Nessim ^{[1
,9
]}

Haeder, Antje ^{[10
,11
]}

Kurzai, Oliver ^{[10
,11
]}

Luo, Ting ^{[12
]}

Krueger, Thomas ^{[12
]}

Kniemeyer, Olaf ^{[12
]}

Cota, Ernesto ^{[9
]}

Bader, Oliver ^{[13
]}

Wheeler, Robert T. ^{[5
]}

Gutsmann, Thomas ^{[3
]}

Hube, Bernhard ^{[2
,14
,15
]}

Naglik, Julian R. ^{[1
]}

机构：

[1] Kings Coll London, Inst Dent, Mucosal & Salivary Biol Div, London SE1 1UL, England

[2] Hans Knoell Inst, Dept Microbial Pathogen Mech, D-07745 Jena, Germany

[3] Res Ctr Borstel, Div Biophys, D-23845 Borstel, Germany

[4] Deutsch Elektronen Synchrotron DESY, D-22607 Hamburg, Germany

[5] Univ Maine, Dept Mol & Biomed Sci, Orono, ME 04469 USA

[6] Kings Coll London, Wolfson CARD, Guys Campus, London SE1 1UL, England

[7] Hans Knoell Inst, Res Grp Microbial Immunol, D-07745 Jena, Germany

[8] Kings Coll London, Ctr Ultrastruct Imaging, London SE1 1UL, England

[9] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London SW7 2AZ, England

[10] Hans Knoell Inst, Sept Res Ctr, D-07745 Jena, Germany

[11] Univ Jena, D-07745 Jena, Germany

[12] Hans Knoell Inst, Dept Mol & Appl Microbiol, D-07745 Jena, Germany

[13] Univ Med Ctr Gottingen, Inst Med Microbiol, D-37075 Gottingen, Germany

[14] Univ Jena, D-07737 Jena, Germany

[15] Integrated Res & Treatment Ctr, Ctr Sepsis Control & Care, D-07747 Jena, Germany

[16] Univ Aberdeen, Sch Med Med Sci & Nutr, Aberdeen Fungal Grp, Aberdeen AB25 2ZD, Scotland

[17] Guys & St Thomas NHS Fdn Trust, NIHR Biomed Res Ctr, London SE1 1UL, England

[18] Univ Valencia, ERI Biotecmed & Microbiol & Ecol Dept, E-46100 Valencia, Spain

来源：

NATURE | 2016年 / 532卷 / 7597期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金; 英国医学研究理事会; 美国国家卫生研究院;

关键词：

PROTEIN-KINASE HOMOLOG; SACCHAROMYCES-CEREVISIAE; HYPHAL DEVELOPMENT; EPITHELIAL-CELLS; OROPHARYNGEAL CANDIDIASIS; PATHOGENICITY MECHANISMS; TRANSCRIPTION FACTOR; BETA-MANNOSYLATION; FILAMENTOUS GROWTH; ALBICANS ENCODES;

D O I：

10.1038/nature17625

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：64 / +

页数：22

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