Genomic analysis and identification of a novel superantigen, SargEY, in <i>Staphylococcus argenteus</i> isolated from atopic dermatitis lesions

<jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title/> <jats:p> During surveillance of <jats:italic>Staphylococcus aureus</jats:italic> in lesions from patients with atopic dermatitis (AD), we isolated <jats:italic>Staphylococcus argenteus</jats:italic> , a species registered in 2011 as a new member of the genus <jats:italic>Staphylococcus</jats:italic> and previously considered a lineage of <jats:italic>S. aureus</jats:italic> . Genome sequence comparisons between <jats:italic>S. argenteus</jats:italic> isolates and representative <jats:italic>S. aureus</jats:italic> clinical isolates from various origins revealed that the <jats:italic>S. argenteus</jats:italic> genome from AD patients closely resembles that of <jats:italic>S. aureus</jats:italic> causing skin infections. We previously reported that 17%–22% of <jats:italic>S. aureus</jats:italic> 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 <jats:italic>S. argenteus</jats:italic> isolates revealed a gene encoding a protein similar to superantigen SEY, designated as SargEY, on its chromosome. Population structure analysis of <jats:italic>S. argenteus</jats:italic> revealed that these isolates are ST2250 lineage, which was the only lineage positive for the SEY-like gene among <jats:italic>S. argenteus</jats:italic> . Recombinant SargEY demonstrated immunological cross-reactivity with anti-SEY serum. SargEY could induce proliferation of human CD4 <jats:sup>+</jats:sup> and CD8 <jats:sup>+</jats:sup> T cells, as well as production of TNF-α and IFN-γ. SargEY showed emetic activity in a marmoset monkey model. S <jats:sub>arg</jats:sub> EY 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. S <jats:sub>arg</jats:sub> EY and SEY may play roles in exacerbating the respective toxin-producing strains in AD. </jats:p> </jats:sec> <jats:sec> <jats:title>IMPORTANCE</jats:title> <jats:p> <jats:italic>Staphylococcus aureus</jats:italic> is frequently isolated from active lesions of atopic dermatitis (AD) patients. We reported that 17%–22% of <jats:italic>S. aureus</jats:italic> isolated from AD patients produced a novel superantigen staphylococcal enterotoxin Y (SEY). Unlike many <jats:italic>S</jats:italic> . <jats:italic>aureus</jats:italic> superantigens that activate T cells via T-cell receptor (TCR) Vß, SEY activates T cells via TCR Vα and stimulates cytokine secretion. <jats:italic>Staphylococcus argenteus</jats:italic> was isolated from AD patients during the surveillance for <jats:italic>S. aureus</jats:italic> . Phylogenetic comparison of the genome indicated that the isolate was very similar to <jats:italic>S. aureus</jats:italic> 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 <jats:italic>S. argenteus</jats:italic> harboring a superantigen SargEY gene may be a novel staphylococcal clone that infects human skin and is involved in the exacerbation of AD. </jats:p> </jats:sec>