Neutralization of staphylococcal enterotoxin B by an aptamer antagonist.

Abstract

Staphylococcal enterotoxin B (SEB) is a major virulence factor for staphylococcal toxic shock syndrome (TSS). SEB activates a large subset of the T lymphocytic population, releasing proinflammatory cytokines. Blocking SEB-initiated toxicity may be an effective strategy for treating TSS. Using a process known as systematic evolution of ligands by exponential enrichment (SELEX), we identified an aptamer that can antagonize SEB with nanomolar binding affinity (Kd = 64 nM). The aptamer antagonist effectively inhibits SEB-mediated proliferation and cytokine secretion in human peripheral blood mononuclear cells. Moreover, a PEGylated aptamer antagonist significantly reduced mortality in a "double-hit" mouse model of SEB-induced TSS, established via sensitization with d-galactosamine followed by SEB challenge. Therefore, our novel aptamer antagonist may offer potential therapeutic efficacy against SEB-mediated TSS.

• Authors: Kaiyu Wang, Longjie Gan, Li Jiang, Xianhui Zhang, Xiangyue Yang, Min Chen, Xiaopeng Lan
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 4 Pg. 2072-7 (Apr 2015) ISSN: 1098-6596 [Electronic] United States
• PMID: 25624325 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Cytokines
• Enterotoxins
• enterotoxin B, staphylococcal
• Galactosamine

Topics

• Animals
• Cell Proliferation (drug effects)
• Cloning, Molecular
• Computational Biology
• Cytokines (biosynthesis)
• Drug Evaluation, Preclinical
• Enterotoxins (antagonists & inhibitors)
• Female
• Galactosamine (pharmacology)
• Humans
• Mice
• Mice, Inbred BALB C
• Monocytes (drug effects)
• SELEX Aptamer Technique
• Shock, Septic (drug therapy, microbiology)