Inhibition of the superantigenic activities of Staphylococcal enterotoxin A by an aptamer antagonist

Staphylococcal enterotoxin A (SEA) is an important component of Staphylococcus aureus pathogenesis. SEA induces T lymphocytes activation and proliferation, resulting in the release of a large number of inflammatory cytokines. Blocking the toxic cascade triggered by SEA may be an effective strategy f...

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Bibliographic Details
Published inToxicon (Oxford) Vol. 119; pp. 21 - 27
Main Authors Wang, Kaiyu, Wu, Dong, Chen, Zhuang, Zhang, Xianhui, Yang, Xiangyue, Yang, Chaoyong James, Lan, Xiaopeng
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.09.2016
Subjects
Animals
Antigens, Bacterial - immunology
Aptamer
Aptamers, Peptide - pharmacology
Blood
Cells, Cultured
Cytokines
Diseases
Enterotoxins - antagonists & inhibitors
Enterotoxins - immunology
Evolution
Female
Humans
Ligands
Lymphocytes
Mice
Mice, Inbred BALB C
SELEX
Staphylococcal enterotoxin A
Staphylococcus aureus
Strategy
Superantigen
Superantigen
Aptamer
Staphylococcal enterotoxin A
SELEX
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Summary:Staphylococcal enterotoxin A (SEA) is an important component of Staphylococcus aureus pathogenesis. SEA induces T lymphocytes activation and proliferation, resulting in the release of a large number of inflammatory cytokines. Blocking the toxic cascade triggered by SEA may be an effective strategy for the treatment of SEA-induced diseases. Through a systematic evolution of ligands by exponential enrichment process, we obtained an aptamer (S3) that could bind SEA with both high affinity and specificity, with a Kd value 36.93 ± 7.29 nM (n = 3). This aptamer antagonist effectively inhibited SEA-mediated human peripheral blood mononuclear cells proliferation and inflammatory cytokines (IFN-γ, TNF-α, IL-2 and IL-6) secretion. Moreover, PEGylated S3 significantly reduced mortality in murine lethal toxic shock models established by lipopolysaccharide-potentiated SEA. Therefore, this novel aptamer antagonist has the potential to become a new strategy for treating S. aureus infections and SEA-induced diseases. •Aptamers are selected against Staphylococci enterotoxin A (SEA).•The aptamers exhibit high affinity binding to SEA.•The most potent aptamer efficiently blocks superantigen activity of SEA.
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ISSN:0041-0101
1879-3150
DOI:10.1016/j.toxicon.2016.05.006