Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor antagonists

Rebecca A. Buonpane, Hywyn R.O. Churchill, Beenu Moza, Eric J. Sundberg, Marnie L. Peterson, Patrick M. Schlievert, David M. Kranz

Research output: Contribution to journalArticle

Abstract

Exotoxins of Staphylococcus aureus belong to a family of bacterial proteins that act as superantigens by activating a large subset of the T-cell population, causing massive release of inflammatory cytokines. This cascade can ultimately result in toxic shock syndrome and death. Therapeutics targeting the early stage of the pathogenic process, when the superantigen binds to its receptor, could limit the severity of disease. We engineered picomolar binding affinity agents to neutralize the potent toxin staphylococcal enterotoxin B (SEB). A single immunoglobulin-like domain of the T-cell receptor (variable region, VΒ) was subjected to multiple rounds of directed evolution using yeast display. Soluble forms of the engineered VΒ proteins produced in Escherichia coli were effective inhibitors of SEB-mediated T-cell activation and completely neutralized the lethal activity of SEB in animal models. These VΒ proteins represent an easily produced potential treatment for diseases mediated by bacterial superantigens.

Original languageEnglish (US)
Pages (from-to)725-729
Number of pages5
JournalNature Medicine
Volume13
Issue number6
DOIs
StatePublished - Jun 1 2007

Fingerprint

Superantigens
T-cells
Exotoxins
Bacterial Proteins
Poisons
T-Lymphocyte Subsets
Septic Shock
T-Cell Antigen Receptor
Yeast
Escherichia coli
Staphylococcus aureus
Immunoglobulins
Animals
Proteins
Animal Models
Yeasts
Chemical activation
Display devices
Cytokines
T-Lymphocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Buonpane, R. A., Churchill, H. R. O., Moza, B., Sundberg, E. J., Peterson, M. L., Schlievert, P. M., & Kranz, D. M. (2007). Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor antagonists. Nature Medicine, 13(6), 725-729. https://doi.org/10.1038/nm1584

Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor antagonists. / Buonpane, Rebecca A.; Churchill, Hywyn R.O.; Moza, Beenu; Sundberg, Eric J.; Peterson, Marnie L.; Schlievert, Patrick M.; Kranz, David M.

In: Nature Medicine, Vol. 13, No. 6, 01.06.2007, p. 725-729.

Research output: Contribution to journalArticle

Buonpane, RA, Churchill, HRO, Moza, B, Sundberg, EJ, Peterson, ML, Schlievert, PM & Kranz, DM 2007, 'Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor antagonists', Nature Medicine, vol. 13, no. 6, pp. 725-729. https://doi.org/10.1038/nm1584
Buonpane RA, Churchill HRO, Moza B, Sundberg EJ, Peterson ML, Schlievert PM et al. Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor antagonists. Nature Medicine. 2007 Jun 1;13(6):725-729. https://doi.org/10.1038/nm1584
Buonpane, Rebecca A. ; Churchill, Hywyn R.O. ; Moza, Beenu ; Sundberg, Eric J. ; Peterson, Marnie L. ; Schlievert, Patrick M. ; Kranz, David M. / Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor antagonists. In: Nature Medicine. 2007 ; Vol. 13, No. 6. pp. 725-729.
@article{d8af5373e12947bab2d198a3cb0db818,
title = "Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor antagonists",
abstract = "Exotoxins of Staphylococcus aureus belong to a family of bacterial proteins that act as superantigens by activating a large subset of the T-cell population, causing massive release of inflammatory cytokines. This cascade can ultimately result in toxic shock syndrome and death. Therapeutics targeting the early stage of the pathogenic process, when the superantigen binds to its receptor, could limit the severity of disease. We engineered picomolar binding affinity agents to neutralize the potent toxin staphylococcal enterotoxin B (SEB). A single immunoglobulin-like domain of the T-cell receptor (variable region, VΒ) was subjected to multiple rounds of directed evolution using yeast display. Soluble forms of the engineered VΒ proteins produced in Escherichia coli were effective inhibitors of SEB-mediated T-cell activation and completely neutralized the lethal activity of SEB in animal models. These VΒ proteins represent an easily produced potential treatment for diseases mediated by bacterial superantigens.",
author = "Buonpane, {Rebecca A.} and Churchill, {Hywyn R.O.} and Beenu Moza and Sundberg, {Eric J.} and Peterson, {Marnie L.} and Schlievert, {Patrick M.} and Kranz, {David M.}",
year = "2007",
month = "6",
day = "1",
doi = "10.1038/nm1584",
language = "English (US)",
volume = "13",
pages = "725--729",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor antagonists

AU - Buonpane, Rebecca A.

AU - Churchill, Hywyn R.O.

AU - Moza, Beenu

AU - Sundberg, Eric J.

AU - Peterson, Marnie L.

AU - Schlievert, Patrick M.

AU - Kranz, David M.

PY - 2007/6/1

Y1 - 2007/6/1

N2 - Exotoxins of Staphylococcus aureus belong to a family of bacterial proteins that act as superantigens by activating a large subset of the T-cell population, causing massive release of inflammatory cytokines. This cascade can ultimately result in toxic shock syndrome and death. Therapeutics targeting the early stage of the pathogenic process, when the superantigen binds to its receptor, could limit the severity of disease. We engineered picomolar binding affinity agents to neutralize the potent toxin staphylococcal enterotoxin B (SEB). A single immunoglobulin-like domain of the T-cell receptor (variable region, VΒ) was subjected to multiple rounds of directed evolution using yeast display. Soluble forms of the engineered VΒ proteins produced in Escherichia coli were effective inhibitors of SEB-mediated T-cell activation and completely neutralized the lethal activity of SEB in animal models. These VΒ proteins represent an easily produced potential treatment for diseases mediated by bacterial superantigens.

AB - Exotoxins of Staphylococcus aureus belong to a family of bacterial proteins that act as superantigens by activating a large subset of the T-cell population, causing massive release of inflammatory cytokines. This cascade can ultimately result in toxic shock syndrome and death. Therapeutics targeting the early stage of the pathogenic process, when the superantigen binds to its receptor, could limit the severity of disease. We engineered picomolar binding affinity agents to neutralize the potent toxin staphylococcal enterotoxin B (SEB). A single immunoglobulin-like domain of the T-cell receptor (variable region, VΒ) was subjected to multiple rounds of directed evolution using yeast display. Soluble forms of the engineered VΒ proteins produced in Escherichia coli were effective inhibitors of SEB-mediated T-cell activation and completely neutralized the lethal activity of SEB in animal models. These VΒ proteins represent an easily produced potential treatment for diseases mediated by bacterial superantigens.

UR - http://www.scopus.com/inward/record.url?scp=34250000045&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250000045&partnerID=8YFLogxK

U2 - 10.1038/nm1584

DO - 10.1038/nm1584

M3 - Article

C2 - 17515896

AN - SCOPUS:34250000045

VL - 13

SP - 725

EP - 729

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 6

ER -