Staphylococcus hyicus exfoliative toxins selectively digest porcine desmoglein 1

Staphylococcus hyicus exfoliative toxins selectively digest porcine desmoglein 1
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DOI:
10.1016/j.micpath.2005.08.003
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发表时间:
2005-11-01
影响因子:
3.8
通讯作者:
Sugai, M
Sugai, M
中科院分区:
医学3区
文献类型:
--
作者:
Fudaba, Y;Nishifuji, K;Sugai, M

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猪葡萄球菌的毒力菌株可引起猪的渗出性表皮炎。这种疾病的主要症状是棘层上部的皮肤脱落。皮肤的剥脱与剥脱性毒素(包括ExhA、ExhB、ExhC、ExhD、SHETA和SHETB)强烈相关。最近,ExhA、ExhB、ExhC和ExhD的基因被克隆。S.金黄色葡萄球菌已经显示出选择性地切割人或小鼠桥粒芯糖蛋白1(一种桥粒粘附分子),其在失活时导致水泡。在这项研究中,我们试图确定Exhs在猪皮肤中的分子靶点。每种注射到猪皮肤中的重组Exhs均引起浅表表皮水疱或结痂形成。细胞表面染色的桥粒芯糖蛋白1,但不是桥粒芯糖蛋白3,被废除时,冷冻切片的正常猪皮肤孵育的Exh之一,表明Exh选择性降解猪桥粒芯糖蛋白1。人、小鼠或犬来源的桥粒芯糖蛋白I和桥粒芯糖蛋白3的重组细胞外结构域的体外孵育证明仅小鼠桥粒芯糖蛋白1 α和1 β被高浓度的ExhA和ExhC切割。此外,注射高浓度ExhA和ExhC引起新生小鼠的浅表水泡。这些发现有力地表明,Exhs通过消化猪桥粒芯糖蛋白I以类似于来自S.金黄色。(C)2005 Elsevier Ltd.保留所有权利。
Virulent strains of Staphylococcus hyicus can cause exudative epidermitis in pigs. The major symptom of this disease is exfoliation of the skin in the upper stratum spinosum. Exfoliation of the skin is strongly associated with exfoliative toxin including ExhA, ExhB, ExhC, ExhD, SHETA, and SHETB. Recently, genes for ExhA, ExhB, ExhC and ExhD were cloned. Exfoliative toxins produced by S. aureus have been shown to selectively cleave human or mouse desmoglein 1, a desmosomal adhesion molecule, that when inactivated results in blisters. In this study, we attempted to identify the molecular target of Exhs in porcine skin. Each of recombinant Exhs injected in the skin of pigs caused superficial epidermal blisters or crust formation. Cell surface staining of desmoglein 1, but not that of desmoglein 3, was abolished when cryosections of normal porcine skin were incubated with one of Exhs suggesting that Exh selectively degrade porcine desmoglein 1. In vitro incubation of the recombinant extracellular domains of desmoglein I and desmoglein 3 of human, mouse or canine origin demonstrated that only mouse desmogleins 1 alpha and 1 beta were cleaved by ExhA and ExhC at high concentration. Furthermore, injection of ExhA and ExhC at high concentration caused superficial blisters in neonatal mice. These findings strongly suggest that Exhs cause blister formation of porcine skin by digesting porcine desmoglein I in a similar fashion to exfoliative toxins from S. aureus. (C) 2005 Elsevier Ltd. All rights reserved.