Journal article
Engineering a soluble high-affinity receptor domain that neutralizes staphylococcal enterotoxin C in rabbit models of disease
Protein engineering, design and selection, Vol.26(2), pp.133-142
02/2013
DOI: 10.1093/protein/gzs094
PMCID: PMC3542526
PMID: 23161916
Abstract
Superantigens (SAgs) are a class of immunostimulatory exotoxins that activate large numbers of T cells, leading to overproduction of cytokines and subsequent inflammatory reactions and systemic toxicity. Staphylococcal enterotoxin C (SEC), a SAg secreted by
Staphylococcus aureus
, has been implicated in various illnesses including non-menstrual toxic shock syndrome (TSS) and necrotizing pneumonia. SEC has been shown to cause TSS illness in rabbits and the toxin contributes to lethality associated with methicillin-resistant
S.aureus
(MRSA) in a rabbit model of pneumonia. With the goal of reducing morbidity and mortality associated with SEC, a high-affinity variant of the extracellular variable domain of the T-cell receptor beta-chain for SEC (∼14 kDa) was generated by directed evolution using yeast display. This protein was characterized biochemically and shown to cross-react with the homologous (65% identical) SAg staphylococcal enterotoxin B (SEB). The soluble, high-affinity T-cell receptor protein neutralized SEC and SEB
in vitro
and also significantly reduced the bacterial burden of an SEC-positive strain of MRSA (USA400 MW2) in an infective endocarditis model. The neutralizing agent also prevented lethality due to MW2 in a necrotizing pneumonia rabbit model. These studies characterize a soluble high-affinity neutralizing agent against SEC, which is cross-reactive with SEB, and that has potential to be used intravenously with antibiotics to manage staphylococcal diseases that involve these SAgs.
Details
- Title: Subtitle
- Engineering a soluble high-affinity receptor domain that neutralizes staphylococcal enterotoxin C in rabbit models of disease
- Creators
- D.M Mattis - ,A.R Spaulding - ,O.N Chuang-Smith - ,E.J Sundberg - ,P.M Schlievert - ,D.M Kranz - ,
- Resource Type
- Journal article
- Publication Details
- Protein engineering, design and selection, Vol.26(2), pp.133-142
- Publisher
- Oxford University Press
- DOI
- 10.1093/protein/gzs094
- PMID
- 23161916
- PMCID
- PMC3542526
- ISSN
- 1741-0126
- eISSN
- 1741-0134
- Language
- English
- Date published
- 02/2013
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001137302771
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