Staphylococcus aureus Isolated from Skin from Atopic-Dermatitis Patients Produces Staphylococcal Enterotoxin Y, Which Predominantly Induces T-Cell Receptor Vα-Specific Expansion of T Cells
Staphylococcus aureus Isolated from Skin from Atopic-Dermatitis Patients Produces Staphylococcal Enterotoxin Y, Which Predominantly Induces T-Cell Receptor Vα-Specific Expansion of T Cells
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DOI：
10.1128/iai.00360-19
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发表时间：
2020-02-01
影响因子：
3.1
通讯作者：
Sugai, Motoyuki
中科院分区：
文献类型：
--
作者：
Aziz, Fatkhanuddin;Hisatsune, Junzo;Sugai, Motoyuki
在研究粘附于特应性皮炎（AD）患者皮肤的金黄色葡萄球菌的毒力特征时，我们从AD皮肤分离株的基因组序列数据中鉴定了一个与超抗原结构相似的新开放阅读框架（ORF）。同时，在牛分离的S.金黄色葡萄球菌，命名为SElY（H. K. Ono，Y. Sato'o，K.成田岛Naito等人，Appl Environ Microbiol 81：7034 - 7040，2015，https：//doi.org/10.1128/AEM.01873-15）。重组SElYbov在人外周血单个核细胞中具有超抗原活性。它在灵长类动物模型中进一步证明了催吐活性，并建议将SElY重新命名为SEY（H. K. Ono，S.广罗斯K。Narita，M. Sugiyama等人，PLoS Pathog 15：e1007803，2019，https：//doi.org/10.1371/journal.ppat.1007803）。在这里，我们调查了日本不同来源的270株人类临床分离株中sey基因的患病率。42株菌株的sey基因呈阳性，阳性菌株来自特应性皮炎和脓疱/葡萄球菌烫伤样皮肤综合征（SSSS）的皮肤病患者，检出率为17%至22%。SEY有三种变体（SEY 1、SEY 2和SEY 3），产生SEY变体的分离物形成三个不同的簇，分别对应于克隆复合物（CC）121、59和20。大多数SEY（+）菌株在肉汤培养中产生SEY。与SEYbov不同，三种重组SEY变体表现出对热处理的稳定性。SEY主要激活具有特定T细胞受体（TCR）V α谱的人T细胞，这是一个独特的观察结果，因为大多数葡萄球菌肠毒素通过激活具有特定TCR V β谱的T细胞发挥其超抗原活性。SEY可能通过皮肤驻留T细胞活化诱导局部炎症，促进S.金黄色葡萄球菌感染破坏上皮屏障。
While investigating the virulence traits of Staphylococcus aureus adhering to the skin of atopic-dermatitis (AD) patients, we identified a novel open reading frame (ORF) with structural similarity to a superantigen from genome sequence data of an isolate from AD skin. Concurrently, the same ORF was identified in a bovine isolate of S. aureus and designated SElY (H. K. Ono, Y. Sato'o, K. Narita, I. Naito, et al., Appl Environ Microbiol 81:7034 -7040, 2015, https://doi.org/10.1128/AEM.01873-15). Recombinant SElYbov had superantigen activity in human peripheral blood mononuclear cells. It further demonstrated emetic activity in a primate animal model, and it was proposed that SElY be renamed SEY (H. K. Ono, S. Hirose, K. Narita, M. Sugiyama, et al., PLoS Pathog 15:e1007803, 2019, https://doi.org/10.1371/journal.ppat.1007803). Here, we investigated the prevalence of the sey gene in 270 human clinical isolates of various origins in Japan. Forty-two strains were positive for the sey gene, and the positive isolates were from patients with the skin diseases atopic dermatitis and impetigo/ staphylococcal scalded skin syndrome (SSSS), with a detection rate of similar to 17 to 22%. There were three variants of SEY (SEY1, SEY2, and SEY3), and isolates producing SEY variants formed three distinct clusters corresponding to clonal complexes (CCs) 121, 59, and 20, respectively. Most sey(+) isolates produced SEY in broth culture. Unlike SEYbov, the three recombinant SEY variants exhibited stability against heat treatment. SEY predominantly activated human T cells with a particular T-cell receptor (TCR) V alpha profile, a unique observation since most staphylococcal enterotoxins exert their superantigenic activities through activating T cells with specific TCR V beta profiles. SEY may act to induce localized inflammation via skin-resident T-cell activation, facilitating the pathogenesis of S. aureus infection in disrupted epithelial barriers.