Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The exotoxins produced by Staphylococcus aureus, staphylococcal enterotoxins (SE) A-E and toxic shock syndrome toxin (TSST)-1, which are associated with serious diseases, including food poisoning and toxic shock syndrome, are termed superantigens (SAgs). To examine whether common antigenic epitopes were present and whether vaccination with 1 bacterial SAg could protect against challenge with a different SE or TSST-1, mice were vaccinated with SEA, SEB, SEC1, or TSST-1 individually or in combination. Mice injected with a single toxin developed high antibody titers against other SAgs. Marked improvement in survival was observed when immunized mice were challenged with a heterologous toxin. Mice vaccinated with a mixture of toxins were fully protected against 1 or multiple toxin challenges, indicating no interference effects of multivalent vaccinations. More importantly, higher titers were found against each SAg with the multivalent vaccination than with injection with a single SAg. Thus, immunizations with 1 SAg can induce cross-protective antibodies to heterologous SAgs, and multicomponent vaccination can enhance antibody responses against each bacterial SAg.
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PMID:Cross-reactive antibodies prevent the lethal effects of Staphylococcus aureus superantigens. 1047 74

Recently, in Japan newly neonatal exanthematous disease was elucidated to be caused by staphyloccocal supcrantigcnic exotoxins, mainly TSST-1. We studied exotoxins producibility of 43 strains of S. aureus isolated from neonates with exanthematous disease and examined antibody titers to staphylococcal enterotoxin A, B, C (SEA, SEB, SEC) and toxic shock syndrome toxin 1 (TSST-1) of the patients and control (umbilical cord blood from term infants). The results were as follows 1.34 of 43 strains (79%) isolated from the patients were SEC and TSST-1 producing MRSA, 5 strains (12%) were SEB, SEC, and TSST-1 producing MRSA, 1 strain (2%) was SEB and TSST-1 producing MRSA, 2 strains (12%) were SEB producing MSSA and did not produce TSST-1. The 1 strain (2%) was MSSA which produced SEC and TSST-1. 2. 16 neonates with exanthematous disease, who showed typical clinical signs and laboratry findings of thrombocytopenia, with SEC and TSST-1 producing MRSA isolates had significantly low anti-TSST-1 antibody titers at onset (p < 0.05), compared with the control (umbilical cord blood from term infants): TSST-1 appeared to the causative agent for the disease. In two neonates with exanthematous disease, with SEB- and non- TSST-1-producing MSSA isolates, anti-SEB antibody titers were low at onset, so SEB appeared to the causative agent for the disease. 3. In Japan, low anti-TSST-1 antibody titers were found in the umbilical blood samples from about 70% of term infants; and low anti-SEB or anti-SEC antibody titers were found in samples from only about 10% of them, that is, a number of term infants had anti-SEB and anti-SEC antibodies. The majority of S. aureus isolated from neonates with exanthematous disease were enterotoxin- and TSST-1-producing MRSAs. The results of our study by measuring antitoxin antibody titers suggested that SEB and SEC might not be pathogenically responsible, but TSST-1 was considered to be responsible for the majority of exanthematous disease. Prevalence of TSST-1-producing MRSA in the neonatal and premature baby ward is the main cause for the high incidence of this disease in Japan, whereas the low antibody titer to TSST-1 in the mother, in comparison with the anti-enterotoxin antibody titers, may also be a predisposing factor.
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PMID:[A new exanthematous disease in newborn infants caused by exotoxins producing Staphylococcus aureus; exotoxins production of the isolates and serum levels of antitoxin antibody in the patients and umbilical cord blood]. 1053 64

Staphylococcal exotoxins, staphylococcal enterotoxins A-E (SEA-SEE), and toxic shock syndrome toxin- (TSST-1) are potent activators of the immune system and cause a variety of diseases in humans, ranging from food poisoning to shock. These toxins are called superantigens because of their ability to polyclonally activate T cells at picromolar concentrations. Superantigens bind to both MHC class II molecules and specific Vbeta regions of the T cell receptor, leading to the activation of both antigen-presenting cells and T lymphocytes. These interactions lead to excessive production of proinflammatory cytokines and T cell proliferation, causing clinical symptoms that include fever, hypotension, and shock. Recent studies suggest that staphylococcal superantigens may also be involved in the pathogenesis of arthritis and other autoimmune disorders. This review summarizes the in vitro and in vivo effects of staphylococcal enterotoxins and TSST-1, recent progress with the use of transgenic knockout mice to identify key mediators and receptors involved in superantigen-induced shock, and therapeutic agents to mitigate the toxic effects of staphylococcal superantigens.
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PMID:Immune response to staphylococcal superantigens. 1058 Jun 40

This article reviews the literature regarding the structure and function of two types of exotoxins expressed by Staphylococcus aureus, pyrogenic toxin superantigens (PTSAgs) and hemolysins. The molecular basis of PTSAg toxicity is presented in the context of two diseases known to be caused by these exotoxins: toxic shock syndrome and staphylococcal food poisoning. The family of staphylococcal PTSAgs presently includes toxic shock syndrome toxin-1 (TSST-1) and most of the staphylococcal enterotoxins (SEs) (SEA, SEB, SEC, SED, SEE, SEG, and SEH). As the name implies, the PTSAgs are multifunctional proteins that invariably exhibit lethal activity, pyrogenicity, superantigenicity, and the capacity to induce lethal hypersensitivity to endotoxin. Other properties exhibited by one or more staphylococcal PTSAgs include emetic activity (SEs) and penetration across mucosal barriers (TSST-1). A detailed review of the molecular mechanisms underlying the toxicity of the staphylococcal hemolysins is also presented.
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PMID:Exotoxins of Staphylococcus aureus. 1062 89

A simple polymerase chain reaction (PCR)-based procedure was developed for the detection of fragments of staphylococcal enterotoxins (SEs) SEA, SEB, SEC, SED, SEE, SEG, SEH, and SEI together with the toxic shock syndrome toxin (TSST-1) genes of Staphylococcus aureus. One hundred and twenty-nine cultures of S. aureus were selected, 39 of which were recovered from 38 suspected staphylococcal food-poisoning incidents. The method was reproducible, and 32 different toxin genotypes were recognized. The presence of SE genes was associated with S. aureus strains reacting with phages in group III, and the TSST-1 gene with phages in group I. There was a 96% agreement between the PCR results for detection of SEA-D and TSST-1 as compared with a commercial reverse passive latex agglutination assay for the detection of SEs from cultures grown in vitro. Enterotoxin gene fragments were detected in S. aureus cultures recovered from 32 of the 38 suspected staphylococcal food poisoning incidents, and of these, 17 were associated with SEE, SEG, SEH, and SEI in the absence of SEA-D. Simple PCR procedures were also developed for the detection of SE directly in spiked food samples, and this was most successfully achieved in mushroom soup and ham. Detection was less successful in three types of cheese and in cream. SEA or SEB were detected by enzyme-linked immunosorbent assay in three food samples (two of which were associated with food poisoning incidents) naturally heavily contaminated with S. aureus: the appropriate SEA or SEB gene fragments were detected directly in these three foods by PCR.
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PMID:The detection of enterotoxins and toxic shock syndrome toxin genes in Staphylococcus aureus by polymerase chain reaction. 1077 13

Staphylococcal superantigens have been implicated in the pathogenesis of atopic dermatitis (AD). This may occur through superantigenic activation of T lymphocytes and their subsequent induction of the skin homing receptor CLA on activated cells. We investigated the proliferative responses of peripheral blood mononuclear cells (PBMC) from 10 patients with an infective exacerbation of AD and six normal controls to the staphylococcal superantigens, staphylococcal enterotoxin A and B (SEA, SEB) and toxic shock syndrome toxin-1 (TSST-1), and the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A). We also assessed CLA and T cell receptor (TCR) Vbeta-chain expression by immunofluorescence and flow cytometry before and after stimulation. PBMC from AD patients showed two-fold increased proliferation to SEA and SEB (P < 0.01) compared with normals, whereas the response to mitogenic stimulation was identical. Analysis of (TCR) Vbeta-chain expression demonstrated increased use of superantigen-reactive Vbeta families in freshly isolated PBMC in AD patients compared with controls. This pattern of Vbeta-chain expression was only observed in the CLA+ but not the total population of T cells. Furthermore, there was a positive correlation between the enhanced PBMC proliferative response and increased expression of superantigen-reactive Vbeta families in atopic patients. These data support the concept that superantigens are important in the pathogenesis of this common condition, and also provide evidence that the increased use of certain Vbeta families in circulating, CLA+, skin homing lymphocytes is of functional significance.
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PMID:Staphylococcal toxin-induced T cell proliferation in atopic eczema correlates with increased use of superantigen-reactive Vbeta-chains in cutaneous lymphocyte-associated antigen (CLA)-positive lymphocytes. 1093 Nov 29

Staphylococcal toxic shock syndrome is caused by a family of related superantigens that includes toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxins (SEs) A, B, and C. The cross-inhibitory activity against SEA by a novel anti-TSST-1 monoclonal antibody (MAb), MAb5, which also cross-inhibits SEB-induced superantigenic activities, was investigated. MAb5 blocked SEA binding to human monocytes, cross-neutralized SEA-induced T cell mitogenesis and TNF-alpha secretion in human peripheral blood mononuclear cells, and prevented lethality in mice. Epitope mapping revealed that MAb5 binds to residues SEA(154-161) within the central alpha helix that is structurally highly conserved among TSST-1, SEA, and SEB. The cross-inhibitory activity of MAb5 is likely due to steric hindrance of this conserved motif, although the precise function of this motif shared among related staphylococcal superantigens remains to be further elucidated.
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PMID:Inhibition of staphylococcal enterotoxin A-induced superantigenic and lethal activities by a monoclonal antibody to toxic shock syndrome toxin-1. 1137 26

In this study, the ability of purified bovine gammadelta T cells in vitro to be activated by superantigens (SAg) was investigated. Freshly isolated WC1(+) gammadelta T cells, in the presence of autologous glutaraldehyde-fixed or gamma-irradiated antigen presenting cells (APC) and IL-2, were incubated with staphylococcal enterotoxins A and B (SEA and SEB), and toxic shock syndrome toxin-1 (TSST-1). Both a proliferative response and the expression of particular T cell receptor genes of the gamma variable (TCR Vgamma) repertoire family were induced. Genes encoding TCR Vgamma1 and TCR Vgamma2 family, but not TCR Vgamma5 were detected. The cells also expressed cytokine transcripts, namely, those of IL-12, IFN-gamma and TNF-alpha, but not IL-2, IL-4, IL-6, IL-7 and IL-10. The activation and proliferation of freshly isolated gammadelta T cells by non-processed antigens required two signals, one originating from the APC and a second dependent on exogenous IL-2. Our results show that purified bovine WC1(+) gammadelta T cells could be driven to proliferate and to express a particular TCRVgamma profile in response to superantigen activation. The possible implication of cytokines expressed by bovine gammadelta T cells in immunopathogenesis is discussed.
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PMID:Purified bovine WC1+ gamma delta T lymphocytes are activated by staphylococcal enterotoxins and toxic shock syndrome toxin-1 superantigens: proliferation response, TCR V gamma profile and cytokines expression. 1137 2

Bacterial superantigens trigger an excessive, Th1-cytokine response leading to toxic shock. We designed a peptide antagonist that inhibits SEB-induced expression of human genes for IL-2, IFN-gamma, and TNF-beta, cytokines that mediate shock. The peptide antagonist shows homology to a beta-strand-hinge-alpha-helix domain that is conserved structurally in superantigens produced by Staphylococcus aureus and Streptococcus pyogenes yet remote from known binding sites for the major histocompatibility class II molecule and T-cell receptor. For Th1-cell activation, superantigens depend on this domain. The peptide protected mice against lethal challenge with SEB or SEA. Moreover, it rescued mice undergoing toxic shock. Surviving mice rapidly developed broad-spectrum, protective immunity, which rendered them resistant to further lethal challenges with different staphylococcal and streptococcal superantigens. Thus, the lethal effect of superantigens, mediated by Th1 cytokines, can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade, before activation of T cells takes place.
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PMID:Superantigen antagonist blocks Th1 cytokine gene induction and lethal shock. 1140 77

Staphylococcal enterotoxins (SE) are exoproteins produced by Staphylococcus aureus that act as superantigens and have been implicated as a leading cause of food-borne disease and toxic shock. Little is known about how these molecules penetrate the gut lining and gain access to both local and systemic immune tissues. To model movement in vitro of staphylococcal enterotoxins, we have employed a monolayer system composed of crypt-like human colonic T-84 cells. SEB and SEA showed comparable dose-dependent transcytosis in vitro, while toxic shock syndrome toxin (TSST-1) exhibited increased movement at lower doses. Synthetic peptides corresponding to specific regions of the SEB molecule were tested in vitro to identify the domain of the protein involved in the transcytosis of SE. A toxin peptide of particular interest contains the amino acid sequence KKKVTAQELD, which is highly conserved across all SE. At a toxin-to-peptide ratio of 1:10, movement of SEB across the monolayers was reduced by 85%. Antisera made against the SEB peptide recognized native SEB and also inhibited SEB transcytosis. Finally, the conserved 10-amino-acid peptide inhibited transcytosis of multiple staphylococcal enterotoxins, SEA, SEE, and TSST-1. These data demonstrate that this region of the staphylococcal enterotoxins plays a distinct role in toxin movement across epithelial cells. It has implications for the prevention of staphylococcal enterotoxin-mediated disease by design of a peptide vaccine that could reduce systemic exposure to oral or inhaled superantigens. Since the sequence identified is highly conserved, it allows for a single epitope blocking the transcytosis of multiple SE.
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PMID:Identification of a transcytosis epitope on staphylococcal enterotoxins. 1189 85


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