Staphylococcus pseudintermedius exfoliative toxin EXI selectively digests canine desmoglein 1 and causes subcorneal clefts in canine epidermis
Staphylococcus pseudintermedius exfoliative toxin EXI selectively digests canine desmoglein 1 and causes subcorneal clefts in canine epidermis
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DOI：
10.1111/j.1365-3164.2011.00952.x
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发表时间：
2011-08-01
影响因子：
1.4
通讯作者：
Nishifuji, Koji
中科院分区：
文献类型：
--
作者：
Iyori, Keita;Futagawa-Saito, Keiko;Nishifuji, Koji
已知葡萄球菌剥脱性毒素可消化桥粒糖蛋白 (Dsg) 1（一种桥粒细胞间粘附分子），从而导致人大疱性脓疱病、葡萄球菌烫伤皮肤综合征和猪渗出性表皮炎的表皮内分裂。最近，从伪中间葡萄球菌中分离出一种新的剥脱性毒素基因（exi），其序列与先前鉴定的剥脱性毒素具有显着的同源性。关于这种毒素在犬脓疱病（例如脓疱病）中的致病作用知之甚少。本研究的目的是确定 exi 基因的产物 EXI 是否会消化犬 Dsg1 并导致犬皮肤表皮内分裂。从患有脓疱疮的狗的脓疱获得的伪中间链球菌菌株的染色体DNA中分离出exi基因，并用于通过大肠杆菌表达产生重组EXI。当纯化的重组EXI皮内注射到正常狗体内时，会引起水疱或糜烂的形成，并伴有浅表表皮分裂。此外，EXI 取消了 Dsg1 的免疫荧光，但没有取消 Dsg3 在注射部位的免疫荧光。此外，在体外，EXI 直接降解杆状病毒分泌的犬 Dsg1 重组胞外结构域，但不降解犬 Dsg3。 EXI 还降解小鼠 Dsg1 alpha 和猪 Dsg1，但不降解人 Dsg1、小鼠 Dsg1 beta 和 Dsg1 gamma。相反，重组 SIET（之前被称为中间链球菌剥脱性毒素）不会引起任何 Dsgs 的表皮内分裂或降解。这些发现表明，EXI具有消化犬Dsg1的蛋白水解活性，该特性可能参与犬脓疱病表皮内分裂的发病机制。
Staphylococcal exfoliative toxins are known to digest desmoglein (Dsg) 1, a desmosomal cell-cell adhesion molecule, thus causing intraepidermal splitting in human bullous impetigo, staphylococcal scalded skin syndrome and swine exudative epidermitis. Recently, a novel exfoliative toxin gene (exi), whose sequence shares significant homology with previously identified exfoliative toxins, was isolated from Staphylococcus pseudintermedius. Little is known about the pathogenic involvement of this toxin in canine pustular diseases such as impetigo. The aim of this study was to determine whether EXI, the product of the exi gene, digests canine Dsg1 and causes intraepidermal splitting in canine skin. An exi gene was isolated from chromosomal DNA of an S. pseudintermedius strain obtained from a pustule of a dog with impetigo, and was used to produce a recombinant EXI by Escherichia coli expression. When purified recombinant EXI was injected intradermally into normal dogs, it caused the development of vesicles or erosions with superficial epidermal splitting. In addition, the EXI abolished immunofluorescence for Dsg1, but not for Dsg3, at the injection sites. Moreover, the EXI directly degraded baculovirus-secreted recombinant extracellular domains of canine Dsg1, but not that of canine Dsg3, in vitro. The EXI also degraded mouse Dsg1 alpha and swine Dsg1, but not human Dsg1, mouse Dsg1 beta and Dsg1 gamma. Conversely, recombinant SIET, previously designated as S. intermedius exfoliative toxin, did not cause intraepidermal splitting or degradation of any Dsgs. These findings indicate that EXI has a proteolytic activity that digests canine Dsg1, and this characteristic might be involved in the pathogenesis of intraepidermal splitting in canine impetigo.