Staphylococcal exfoliative toxin B specifically cleaves desmoglein 1
Staphylococcal exfoliative toxin B specifically cleaves desmoglein 1
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DOI：
10.1046/j.1523-1747.2002.01751.x
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发表时间：
2002-05-01
影响因子：
6.5
通讯作者：
Stanley, JR
中科院分区：
文献类型：
--
作者：
Amagai, M;Yamaguchi, T;Stanley, JR
金黄色葡萄球菌烫伤样皮肤综合征及其局限性形式大疱性脓疱病，表现为由金黄色葡萄球菌产生的脱落毒素A或B引起的浅表表皮水疱形成。最近，我们已经证明，剥脱毒素A特异性切割桥粒粘附分子桥粒芯糖蛋白1，当灭活时导致水泡。在这项研究中，我们确定了剥脱毒素B的靶分子。新生小鼠注射剥脱毒素B可引起表皮表面水疱，破坏桥粒芯糖蛋白1的细胞表面染色，并降解桥粒芯糖蛋白1而不影响桥粒芯糖蛋白3或E-钙粘蛋白。当腺病毒转导的表达外源性小鼠桥粒芯糖蛋白1或桥粒芯糖蛋白3的培养角质形成细胞与脱落毒素B孵育时，桥粒芯糖蛋白1被裂解，而桥粒芯糖蛋白3不被裂解。此外，细胞表面染色的桥粒芯糖蛋白1，但不是桥粒芯糖蛋白3，被取消时，正常人皮肤的冷冻切片与脱落毒素B孵育，这表明活细胞是不必要的脱落毒素B切割桥粒芯糖蛋白1。最后，在体外孵育的重组桥粒芯糖蛋白1和桥粒芯糖蛋白3的胞外结构域与脱落毒素B证明，小鼠和人桥粒芯糖蛋白1，但不是桥粒芯糖蛋白3，直接裂解脱落毒素B以剂量依赖性的方式。这些发现表明，表皮脱落毒素A和表皮脱落毒素B通过相同的分子病理生理机制引起葡萄球菌烫伤样皮肤综合征和大疱性脓疱病的水疱形成。
Staphylococcal scalded skin syndrome and its localized form, bullous impetigo, show superficial epidermal blister formation caused by exfoliative toxin A or B produced by Staphylococcus aureus . Recently we have demonstrated that exfoliative toxin A specifically cleaves desmoglein 1, a desmosomal adhesion molecule, that when inactivated results in blisters. In this study we determine the target molecule for exfoliative toxin B. Exfoliative toxin B injected in neonatal mice caused superficial epidermal blisters, abolished cell surface staining of desmoglein 1, and degraded desmoglein 1 without affecting desmoglein 3 or E-cadherin. When adenovirus-transduced cultured keratinocytes expressing exogenous mouse desmoglein 1 or desmoglein 3 were incubated with exfoliative toxin B, desmoglein 1, but not desmoglein 3, was cleaved. Furthermore, cell surface staining of desmoglein 1, but not that of desmoglein 3, was abolished when cryosections of normal human skin were incubated with exfoliative toxin B, suggesting that living cells were not necessary for exfoliative toxin B cleavage of desmoglein 1. Finally, in vitro incubation of the recombinant extracellular domains of desmoglein 1 and desmoglein 3 with exfoliative toxin B demonstrated that both mouse and human desmoglein 1, but not desmoglein 3, were directly cleaved by exfoliative toxin B in a dose-dependent fashion. These findings demonstrate that exfoliative toxin A and exfoliative toxin B cause blister formation in staphylococcal scalded skin syndrome and bullous impetigo by identical molecular pathophysiologic mechanisms.