CD31 (PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin

被引:49
作者
Bruggisser, Julia [1 ]
Tarek, Basma [1 ]
Wyder, Marianne [1 ]
Mueller, Philipp [2 ]
von Ballmoos, Christoph [2 ]
Witz, Guillaume [3 ,5 ]
Enzmann, Gaby [4 ]
Deutsch, Urban [4 ]
Engelhardt, Britta [4 ]
Posthaus, Horst [1 ,6 ,7 ]
机构
[1] Univ Bern, Vetsuisse Fac, Inst Anim Pathol, Dept Infect Dis & Pathobiol, CH-3012 Bern, Switzerland
[2] Univ Bern, Fac Sci, Dept Chem & Biochem, CH-3012 Bern, Switzerland
[3] Univ Bern, Microscopy Imaging Ctr MIC, CH-3012 Bern, Switzerland
[4] Univ Bern, Fac Med, Theodor Kocher Inst, CH-3012 Bern, Switzerland
[5] Univ Bern, Math Inst, Sci IT Support ScITS, Bern, Switzerland
[6] Univ Bern, Vetsuisse Fac, COMPATH, CH-3012 Bern, Switzerland
[7] Univ Bern, Fac Med, CH-3012 Bern, Switzerland
基金
瑞士国家科学基金会;
关键词
PORE-FORMING TOXINS; ENTERITIS NECROTICANS PIGBEL; ALPHA-TOXIN; IN-VITRO; BINDING; CHOLESTEROL; VIRULENCE; DOMAINS; ICAM-2;
D O I
10.1016/j.chom.2020.05.003
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Clostridium perfringens beta-toxin (CPB) is a highly active beta-pore-forming toxin (beta-PFT) and the essential virulence factor for fatal, necro-hemorrhagic enteritis in animals and humans. The molecular mechanisms involved in CPB's action on its target, the endothelium of small intestinal vessels, are poorly understood. Here, we identify platelet endothelial cell adhesion molecule-1 (CD31 or PECAM-1) as the specific membrane receptor for CPB on endothelial cells. CD31 expression corresponds with the cell-type specificity of CPB, and it is essential for toxicity in cultured cells and mice. Ectopic CD31 expression renders resistant cells and li-posomes susceptible to CPB-induced membrane damage. Moreover, the extracellular Ig6 domain of mouse, human, and porcine CD31 is essential for the interaction with CPB. Hence, our results explain the cell-type specificity of CPB in vitro and in the natural disease caused by C. perfringens type C.
引用
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页码:69 / +
页数:16
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