Identification of the Staphylococcus aureus etd pathogenicity island which encodes a novel exfoliative toxin, ETD, and EDIN-B
Identification of the Staphylococcus aureus etd pathogenicity island which encodes a novel exfoliative toxin, ETD, and EDIN-B
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DOI：
10.1128/iai.70.10.5835-5845.2002
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发表时间：
2002-10-01
影响因子：
3.1
通讯作者：
Sugai, M
中科院分区：
文献类型：
--
作者：
Yamaguchi, T;Nishifuji, K;Sugai, M
我们在金黄色葡萄球菌中发现了一个新的致病岛，它含有与脱落毒素(ET)基因、谷氨酰内肽酶基因和Edin-B基因相似的开放阅读框(ORF)，以及位于hsdM、hsdS(限制和修饰系统)和IS256两侧的噬菌体抗性基因。该基因编码的蛋白质与脱落毒素A(ETA)、脱落毒素B(ETB)和猪葡萄球菌ETB(ShETB)的氨基酸序列同源性分别为40%、59%和68%。在组织学检查中观察到，由ET样基因衍生的重组蛋白注射到新生小鼠体内时，会导致皮肤脱落，表皮上部的细胞与细胞之间的黏附丧失，就像注射ETA或ETB的新生小鼠一样。Western印迹分析表明，该重组蛋白在血清学上与ETA和ETB不同。因此，这个新的ORF编码的产物是金黄色葡萄球菌产生的一个新的ET成员，被命名为ETD。ETD对1日龄雏鸡无致水泡作用。在注射ETD的小鼠皮肤中，桥粒中钙粘附素型细胞间黏附分子桥粒芯糖蛋白1(DSG1)的细胞表面染色被取消，而桥粒糖蛋白3(Dsg3)的细胞表面染色不受影响。此外，DSG1和Dsg3的重组胞外区与重组蛋白的体外孵育表明，小鼠和人的DSG1，而不是Dsg3，都以剂量依赖的方式被直接切割。这些结果表明，ETD和ETA通过相同的病理生理机制诱导水泡的形成。EDIN-B阳性的临床菌株被认为是克隆性相关的，所有检测的Edin-B阳性菌株都是ETD阳性。在18株ETD阳性菌株中，有12株产生胞外ETD。有趣的是，这些菌株主要是从其他感染源分离出来的，而不是来自大疱性脓疱病或葡萄球菌烫伤皮肤综合征的患者。这有力地表明，ETD可能在比先前认为的更广泛的细菌感染中发挥致病作用。
We identified a novel pathogenicity island in Staphylococcus aureus which contains open reading frames (ORFs) similar to the exfoliative toxin (ET) gene, glutamyl endopeptidase gene, and edin-B gene in tandem and the phage resistance gene, flanked by hsdM, hsdS (restriction and modification system), and IS256. The protein encoded by the ET-like gene showed 40, 59, and 68% amino acid sequence identities with exfoliative toxin A (ETA), exfoliative toxin B (ETB), and Staphylococcus hyicus ETB (ShETB), respectively. When injected into neonatal mice, the recombinant protein derived from the ET-like gene induced exfoliation of the skin with loss of cell-to-cell adhesion in the upper part of the epidermis as observed in histological examinations, just as was found in neonatal mice injected with ETA or ETB. Western blot analysis indicated that the recombinant protein is serologically distinct from ETA and ETB. Therefore, the product encoded by this new ORF is a new ET member produced by S. aureus and is termed ETD. ETD did not induce blisters in 1-day-old chickens. In the skins of mice injected with ETD, cell surface staining of desmoglein 1 (Dsg1), a cadherin type cell-to-cell adhesion molecule in desmosomes, was abolished without affecting that of desmoglein 3 (Dsg3). Furthermore, in vitro incubation of the recombinant extracellular domains of Dsg1 and Dsg3 with the recombinant protein demonstrated that both mouse and human Dsg1, but not Dsg3, were directly cleaved in a dose-dependent manner. These results demonstrate that ETD and ETA induce blister formation by identical pathophysiological mechanisms. Clinical strains positive for edin-B were suggested to be clonally associated, and all edin-B-positive strains tested were positive for etd. Among 18 etd-positive strains, 12 produced ETD extracellularly. Interestingly, these strains are mainly isolated from other sources of infections and not from patients with bullous impetigo or staphylococcal scalded-skin syndrome. This strongly suggests that ETD might play a pathogenic role in a broader spectrum of bacterial infections than previously considered.