在特应性皮炎(AD)患者病变中金黄色葡萄球菌的监测期间,我们分离出细菌葡萄球菌,该物种于2011年注册为葡萄球菌属的新成员,以前被认为是金黄色葡萄球菌的谱系。在来自各种来源的细菌链球菌分离株和代表性金黄色葡萄球菌临床分离株之间的基因组序列比较揭示,来自AD患者的细菌链球菌基因组非常类似于引起皮肤感染的金黄色葡萄球菌。我们以前报道,17%-22%的金黄色葡萄球菌从皮肤感染分离产生葡萄球菌肠毒素Y(SEY),其主要通过T细胞受体(TCR)Vα途径诱导T细胞增殖。Argenteus分离株的完整基因组测序揭示了一个编码类似于超抗原SEY的蛋白质的基因,被指定为Sargey,在它的染色体上。S.argenteus的种群结构分析显示,这些分离株是ST2250谱系,这是S.argenteus中唯一的SEY样基因阳性谱系。重组SargEY证明了与抗SEY血清的免疫交叉反应性。SargEY能诱导人CD4+和CD8+T细胞增殖,以及TNF-α和IFN-γ的产生。SargEY在the猴模型中显示出呕吐活性。SargEY和SET(系统发育接近但未表征的SE)揭示了它们在诱导人T细胞增殖时对TCRVα的依赖性。此外,TCR测序揭示了SEH诱导的其他先前未描述的Vα库。SargEY和SEY可能在加剧AD中各自产生毒素的菌株中发挥作用。
目的:特应性皮炎(AD)患者的活动性病变中常分离出金黄色葡萄球菌。我们报道,从AD患者中分离出17%-22%的金黄色葡萄球菌产生了新型超抗原葡萄球菌肠毒素Y(SEY)。与许多通过T细胞受体(TCR)Vβ激活T细胞的金黄色葡萄球菌超抗原不同,SEY通过TCRVα激活T细胞并刺激细胞因子分泌。在监测金黄色葡萄球菌的过程中,从AD患者中分离出金黄色葡萄球菌。基因组的系统发育比较表明,该分离株与引起皮肤感染的金黄色葡萄球菌非常相似。分离物编码一种类似SEY的蛋白,指定Sargey,which,像SEY,通过TCRVα激活T细胞。ST2250是SargEY基因唯一阳性的谱系。ST2250携带超抗原SargEY基因的Argenteus可能是感染人类皮肤并参与AD恶化的新型葡萄球菌克隆。
During surveillance of Staphylococcus aureus in lesions from patients with atopic dermatitis (AD), we isolated Staphylococcus argenteus, a species registered in 2011 as a new member of the genus Staphylococcus and previously considered a lineage of S. aureus. Genome sequence comparisons between S. argenteus isolates and representative S. aureus clinical isolates from various origins revealed that the S. argenteus genome from AD patients closely resembles that of S. aureus causing skin infections. We previously reported that 17%-22% of S. aureus isolated from skin infections produce staphylococcal enterotoxin Y (SEY), which predominantly induces T-cell proliferation via the T-cell receptor (TCR) Vα pathway. Complete genome sequencing of S. argenteus isolates revealed a gene encoding a protein similar to
superantigen SEY, designated as SargEY, on its chromosome. Population structure analysis of S. argenteus revealed that these isolates are ST2250 lineage, which was the only lineage positive for the SEY-like gene among S. argenteus. Recombinant SargEY demonstrated immunological cross-reactivity with anti-SEY serum. SargEY could induce proliferation of human CD4+ and CD8+ T cells, as well as production of TNF-α and IFN-γ. SargEY showed emetic activity in a marmoset monkey model. SargEY and SET (a phylogenetically close but uncharacterized SE) revealed their dependency on TCR Vα in inducing human T-cell proliferation. Additionally, TCR sequencing revealed other previously undescribed Vα repertoires induced by SEH. SargEY and SEY may play roles in exacerbating the respective toxin-producing strains in AD.
OBJECTIVE: Staphylococcus aureus is frequently isolated from active lesions of atopic dermatitis (AD) patients. We reported that 17%-22% of S. aureus isolated from AD patients produced a novel
superantigen staphylococcal enterotoxin Y (SEY). Unlike many S. aureus superantigens that activate T cells via T-cell receptor (TCR) Vß, SEY activates T cells via TCR Vα and stimulates cytokine secretion. Staphylococcus argenteus was isolated from AD patients during the surveillance for S. aureus. Phylogenetic comparison of the genome indicated that the isolate was very similar to S. aureus causing skin infections. The isolate encoded a SEY-like protein, designated SargEY, which, like SEY, activated T cells via the TCR Vα. ST2250 is the only lineage positive for SargEY gene. ST2250 S. argenteus harboring a
superantigen SargEY gene may be a novel staphylococcal clone that infects human skin and is involved in the exacerbation of AD.