Staphylococcal enterotoxin B potentiates LPS-induced hepatic dysfunction in chronically catheterized rats

2001 ◽  
Vol 280 (5) ◽  
pp. G866-G872 ◽  
Author(s):  
David W. A. Beno ◽  
Michael R. Uhing ◽  
Masakatsu Goto ◽  
Yong Chen ◽  
Vanida A. Jiyamapa-Serna ◽  
...  
Keyword(s):  
Liver Dysfunction ◽  
Hepatic Dysfunction ◽  
Hepatic Function ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Physiol Gastrointest Liver ◽  
Enterotoxin B ◽  
Factor Α ◽  
Necrosis Factor

Most models of liver dysfunction in sepsis use endotoxin (lipopolysaccharide; LPS) to induce a pathophysiological response. In our study published in this issue (Beno DWA, Uhing MR, Goto M, Chen Y, Jiyamapa-Serna VA, and Kimura RE. Am J Physiol Gastrointest Liver Physiol 280: G858–G865, 2001), the adverse effect of LPS on hepatic function in vivo was only significant at relatively high LPS doses despite high tumor necrosis factor-α concentrations. However, many patients with sepsis are exposed to multiple bacterial toxins that may augment the immune response, resulting in increased hepatic dysfunction. We have developed a model of polymicrobial sepsis by parentally administering a combination of staphylococcal enterotoxin B (SEB) and LPS. Using this model, we demonstrate that SEB (50 μg/kg) potentiates the effect of LPS-induced hepatic dysfunction as measured by decreased rates of biliary indocyanine green clearance and bile flow. These increases were most pronounced with doses of 10 and 100 μg/kg LPS, doses that by themselves do not induce hepatic dysfunction. This may explain the seemingly increased incidence and severity of liver dysfunction in sepsis, and it suggests that the exclusive use of LPS for replicating septic shock may not be relevant for studies of hepatic dysfunction.

Rapid clearance of the bacterial superantigen staphylococcal enterotoxin B in vivo.

1996 ◽  
Vol 64 (11) ◽  
pp. 4567-4573 ◽  
Author(s):  
R Vabulas ◽  
R Bittlingmaier ◽  
K Heeg ◽  
H Wagner ◽  
T Miethke
Keyword(s):  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Rapid Clearance ◽  
Enterotoxin B ◽  
Bacterial Superantigen

scholarly journals Induction of unresponsiveness and impaired T cell expansion by staphylococcal enterotoxin B in CD28-deficient mice.

1996 ◽  
Vol 183 (6) ◽  
pp. 2481-2488 ◽  
Author(s):  
H W Mittrücker ◽  
A Shahinian ◽  
D Bouchard ◽  
T M Kündig ◽  
T W Mak
Keyword(s):  
T Cells ◽  
T Cell ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Rapid Induction ◽  
Cd28 Costimulation ◽  
Enterotoxin B ◽  
Deficient Mice

We used CD28-deficient mice to analyze the importance of CD28 costimulation for the response against Staphylococcal enterotoxin B (SEB) in vivo. CD28 was necessary for the strong expansion of V beta 8+ T cells, but not for deletion. The lack of expansion was not due to a failure of SEB to activate V beta 8+ T cells, as V beta 8+ T cells from both CD28-/- and CD28+/+ mice showed similar phenotypic changes within the first 24 h after SEB injection and cell cycle analysis showed that an equal percentage of V beta 8+ T cells started to proliferate. However, the phenotype and the state of proliferation of V beta 8+ T cells was different at later time points. Furthermore, in CD28-/- mice injection with SEB led to rapid induction of unresponsiveness in SEB responsive T cells, indicated by a drastic reduction of proliferation after secondary SEB stimulation in vitro. Unresponsiveness could also be demonstrated in vivo, as CD28-/- mice produced only marginal amounts of TNF alpha after rechallenge with SEB. In addition CD28-/- mice were protected against a lethal toxic shock induced by a second injection with SEB. Our results indicate that CD28 costimulation is crucial for the T cell-mediated toxicity of SEB and demonstrate that T cell stimulation in the absence of CD28 costimulation induces unresponsiveness in vivo.

scholarly journals Oral administration of recombinant Bacillus subtilis spores expressing mutant staphylococcal enterotoxin B provides potent protection against lethal enterotoxin challenge

AMB Express ◽  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhile Xiong ◽  
Jialiang Mai ◽  
Fei Li ◽  
Bingshao Liang ◽  
Shuwen Yao ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Oral Administration ◽  
Protective Efficacy ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Mutant Form ◽  
Humoral Immune ◽  
Enterotoxin B ◽  
Recombinant Bacillus Subtilis ◽  
Factor Α

AbstractPathogenicity of Staphylococcus aureus is induced by staphylococcal enterotoxin B (SEB). A mutant form of SEB (mSEB) is immunogenic as well as less toxic. Recombinant mSEB and SEB were expressed in pET28a prokaryotic plasmids. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in mSEB-stimulated macrophages were lower than those in SEB-stimulated macrophages (p < 0.001, p < 0.01 respectively). Using CotC as a fusion protein, we constructed recombinant Bacillus subtilis spores expressing mSEB on the spore surface and evaluated their safety and protective efficacy via mouse models. Oral administration of mSEB-expressing spores increased SEB-specific IgA in feces and SEB-specific IgG1 and IgG2a in the sera, compared with mice in naïve and CotC spore-treated groups (p < 0.001, p < 0.01, p < 0.001 respectively). Six weeks following oral dosing of recombinant spores, significant differences were not found in the serum biochemical indices between the mSEB group and the naïve and CotC groups. Furthermore, oral administration of mSEB spores increased the survival rate by 33.3% in mice intraperitoneally injected with 5 µg of wild-type SEB plus 25 µg lipopolysaccharide (LPS). In summation, recombinant spores stably expressing mSEB were developed, and oral administration of such recombinant spores induced a humoral immune response and provided protection against SEB challenge in mice.

scholarly journals Potent Neutralization of Staphylococcal Enterotoxin B In Vivo by Antibodies that Block Binding to the T-Cell Receptor

2019 ◽  
Vol 431 (21) ◽  
pp. 4354-4367 ◽  
Author(s):  
Gang Chen ◽  
Hatice Karauzum ◽  
Hua Long ◽  
Danielle Carranza ◽  
Frederick W. Holtsberg ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Enterotoxin B ◽  
Potent Neutralization

scholarly journals Measurement of Staphylococcal Enterotoxin B in Serum and Culture Supernatant with a Capture Enzyme-Linked Immunosorbent Assay

2007 ◽  
Vol 14 (9) ◽  
pp. 1094-1101 ◽  
Author(s):  
E. Cook ◽  
X. Wang ◽  
N. Robiou ◽  
B. C. Fries
Keyword(s):  
Immunosorbent Assay ◽  
Staphylococcal Enterotoxin ◽  
Enzyme Linked Immunosorbent Assay ◽  
Staphylococcal Enterotoxin B ◽  
Low Concentrations ◽  
Life Threatening ◽  
Nasal Inhalation ◽  
Enterotoxin B ◽  
Rapid Binding

ABSTRACT Staphylococcal enterotoxin B (SEB) is a select agent because it is a potent mitogen that elicits life-threatening polyclonal T-cell proliferation and cytokine production at very low concentrations. Efforts are in progress to develop therapeutic reagents and vaccines that neutralize or prevent the devastating effects of this toxin. Because of its rapid binding to in vivo receptors, this toxin is difficult to detect in serum. This rapid binding also constitutes a major challenge for the development of effective therapeutic reagents that can neutralize the effects of the toxin in vivo. We have developed a highly sensitive capture enzyme-linked immunosorbent assay that detects SEB in body fluids at very low levels. With this assay, the peak levels of SEB in serum and renal clearance can be measured in mice. After either oral ingestion or nasal inhalation of SEB by mice, this assay documents the transcytosis of SEB across the mucosal membranes into serum within 2 h. Furthermore, this assay was used to compare the SEB levels in different murine models for SEB-induced lethal shock and demonstrated that the coadministration of toxin-enhancing chemicals, such as d-galactosamine and lipopolysaccharide, can alter the peak serum SEB levels. Hence, this assay is a potentially useful tool for the study of the pharmacokinetics of SEB and the effects of potential therapeutic reagents on serum SEB levels.

scholarly journals Effective Treatment of Staphylococcal Enterotoxin B Aerosol Intoxication in Rhesus Macaques by Using Two Parenterally Administered High-Affinity Monoclonal Antibodies

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Daniel Verreault ◽  
Jane Ennis ◽  
Kevin Whaley ◽  
Stephanie Z. Killeen ◽  
Hatice Karauzum ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Nonhuman Primate ◽  
Rhesus Macaques ◽  
Clinical Signs ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Primate Model ◽  
Content Type ◽  
Enterotoxin B

ABSTRACTStaphylococcal enterotoxin B (SEB) is a protein exotoxin found on the cell surface ofStaphylococcus aureusthat is the source for multiple pathologies in humans. When purified and concentrated in aerosol form, SEB can cause an acute and often fatal intoxication and thus is considered a biological threat agent. There are currently no vaccines or treatments approved for human use. Studies with rodent models of SEB intoxication show that antibody therapy may be a promising treatment strategy; however, many have used antibodies only prophylactically or well before any clinical signs of intoxication are apparent. We assessed and compared the protective efficacies of two monoclonal antibodies, Ig121 and c19F1, when administered after aerosol exposure in a uniformly lethal nonhuman primate model of SEB intoxication. Rhesus macaques were challenged using small-particle aerosols of SEB and then were infused intravenously with a single dose of either Ig121 or c19F1 (10 mg/kg of body weight) at either 0.5, 2, or 4 h postexposure. Onset of clinical signs and hematological and cytokine response in untreated controls confirmed the acute onset and potency of the toxin used in the challenge. All animals administered either Ig121 or c19F1 survived SEB challenge, whereas the untreated controls succumbed to SEB intoxication 30 to 48 h postexposure. These results represent the successful therapeuticin vivoprotection by two investigational drugs against SEB in a severe nonhuman primate disease model and punctuate the therapeutic value of monoclonal antibodies when faced with treatment options for SEB-induced toxicity in a postexposure setting.

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