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

Fatkhanuddin Aziz; Junzo Hisatsune; Liansheng Yu; Junko Kajimura; Yusuke Sato'o; Hisaya K Ono; Kanako Masuda; Mika Yamaoka; Siti Isrina Oktavia Salasia; Akio Nakane; Hiroki Ohge; Yoichiro Kusunoki; Motoyuki Sugai

doi:10.1128/IAI.00360-19

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

Infect Immun. 2020 Jan 22;88(2):e00360-19. doi: 10.1128/IAI.00360-19. Print 2020 Jan 22.

Authors

Fatkhanuddin Aziz^{1

2}, Junzo Hisatsune^{1

3}, Liansheng Yu^{1

3}, Junko Kajimura⁴, Yusuke Sato'o⁵, Hisaya K Ono⁶, Kanako Masuda¹, Mika Yamaoka⁴, Siti Isrina Oktavia Salasia⁷, Akio Nakane⁸, Hiroki Ohge⁹, Yoichiro Kusunoki⁴, Motoyuki Sugai^{10

3}

Affiliations

¹ Department of Bacteriology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
² Animal Health Study Program, Department of Bioresources Technology and Veterinary, Vocational College, University of Gadjah Mada, Yogyakarta, Indonesia.
³ Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
⁴ Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan.
⁵ Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
⁶ Laboratory of Zoonoses, Kitasato University School of Veterinary Medicine, Towada, Aomori, Japan.
⁷ Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Gadjah Mada, Yogyakarta, Indonesia.
⁸ Department of Microbiology and Immunology, Hirosaki University, Aomori, Japan.
⁹ Department of Infectious Diseases, Hiroshima University Hospital, Hirsohima, Japan.
¹⁰ Department of Bacteriology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan sugai@niid.go.jp.

Abstract

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 SElY_bov 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 ∼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 SEY_bov, the three recombinant SEY variants exhibited stability against heat treatment. SEY predominantly activated human T cells with a particular T-cell receptor (TCR) Vα profile, a unique observation since most staphylococcal enterotoxins exert their superantigenic activities through activating T cells with specific TCR Vβ 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.

Keywords: Staphylococcus aureus; atopic dermatitis; enterotoxins; superantigens.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Proliferation*
Cluster Analysis
Dermatitis, Atopic / complications*
Enterotoxins / analysis
Enterotoxins / genetics
Enterotoxins / immunology*
Genotype
Humans
Japan
Molecular Typing
Receptors, Antigen, T-Cell / analysis*
Skin / microbiology
Staphylococcal Infections / immunology
Staphylococcal Infections / microbiology*
Staphylococcus aureus / classification
Staphylococcus aureus / genetics
Staphylococcus aureus / immunology
Staphylococcus aureus / isolation & purification*
T-Lymphocyte Subsets / chemistry
T-Lymphocyte Subsets / immunology*

Substances

Enterotoxins
Receptors, Antigen, T-Cell