A purified group a streptococcal pyrogenic exotoxin : physicochemical and biological properties including the enhancement of susceptibility to endotoxin lethal shock
01 Mar 1970-Journal of Experimental Medicine (The Rockefeller University Press)-Vol. 131, Iss: 3, pp 611-628
TL;DR: It is suggested that clinical or subclinical infection with Group A streptococci could prepare the host for fatal shock from Gram- negative infections or the inadvertent injection of small amounts of Gram-negative bacterial endotoxins.
Abstract: Purified pyrogenic exotoxin from Group A streptococcal filtrates ( Streptococcus pyogenes , type 10, strain NY-5) has been characterized primarily as a protein complexed with hyaluronic acid. Amino acid composition and analysis revealed a typical acidic protein with an average molecular weight of 29,000. The purified exotoxin was free of streptolysins O and S, nicotinamide adenine dinucleotidases (NADases), deoxyribonucleases (DNases), mucopeptide, and endotoxins. The biological activity was destroyed when the exotoxin was heated at 65°C for 30 min or boiled for 2 min.
The biological activities investigated were pyrogenicity in rabbits (minimal pyrogenic dose-3 hr, 0.07 µg/kg), lethality in rabbits (LD50, 3500 µg/kg), skin test dose in human skin (> 109 skin test doses, per mg toxin), cytotoxicity of rabbit spleen macrophage (Cytotoxic Index 0.5–10 µg/ml), enhancement of susceptibility to endotoxin shock (in rabbits > 100,000-fold), and antigenic analysis (A-type toxin).
The exotoxin was immunogenic and it was possible, therefore, to immunize animals against the various toxic activities. The immunity was specific for the A-type toxin.
The clinical implications of the highly significant enhancement effect of these exotoxins are discussed. It is suggested that clinical or subclinical infection with Group A streptococci could prepare the host for fatal shock from Gram-negative infections or the inadvertent injection of small amounts of Gram-negative bacterial endotoxins.
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TL;DR: Staphylococcal enterotoxins and a group of related proteins made by Streptococci cause food poisoning and shock in man and animals and it is likely that some or all of the pathological effects of these toxins are caused by their ability to activate quickly so many T cells.
Abstract: Staphylococcal enterotoxins and a group of related proteins made by Streptococci cause food poisoning and shock in man and animals. These proteins share an ability to bind to human and mouse major histocompatibility complex proteins. The complex ligand so formed has specificity for a particular part of T cell receptors, V beta, and by engaging V beta can stimulate many T cells. It is likely that some or all of the pathological effects of these toxins are caused by their ability to activate quickly so many T cells. It is also possible that encounters with such toxins have caused mice, at least, to evolve mechanisms for varying their T cell V beta repertoires, such that they are less susceptible to attack by the toxins.
1,941 citations
TL;DR: The clinical and demographic features of streptococcal bacteremia, myositis, and necrotizing fasciitis will be presented and compared with those of strePTococcal toxic shock syndrome and current concepts of the pathogenesis of invasive streptitiscal infection will also be presented.
Abstract: The late 1980s have witnessed the emergence of severe group A streptococcus (GAS) infection; shock, bacteremia, and acute respiratory distress syndrome are common features, and death has been associated with this infection in 30% of patients. Such infections have now been described in all parts of the United States, Europe, and Australia and have occurred predominantly in otherwise healthy adolescents and adults. The characteristic clinical and laboratory features of the streptococcal toxic shock syndrome include deep-seated infection associated with shock and multiorgan failure. Strains of GAS isolated from patients with invasive disease have been predominantly M types 1 and 3, which produce pyrogenic exotoxin A or B or both. In this report, the clinical and demographic features of streptococcal bacteremia, myositis, and necrotizing fasciitis will be presented and compared with those of streptococcal toxic shock syndrome. Current concepts of the pathogenesis of invasive streptococcal infection will also be presented in terms of the interaction between virulence factors of GAS and host defense mechanisms. Finally, new concepts for future treatment of serious streptococcal infections will be proposed.
650 citations
Cites background from "A purified group a streptococcal py..."
...Pyrogenic exotoxins induce fever in humans and animals and also participate in shock by lowering the threshold for exogenous endotoxin [45-47]....
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TL;DR: The exotoxin produced fever in rabbits and enhanced susceptibility to lethal shock caused by endotoxin and the capacity to suppress synthesis of IgM antibody to sheep erythrocytes.
Abstract: Toxic-shock syndrome (TSS) is believed to be caused by a toxin produced by Staphylococcus aureus. An exotoxin has been identified that is associated with strains of S. aureus isolated from patients with TSS. Coded strains of S. aureus were tested for the presence of the exotoxin by polyacrylamide gel isoelectric focusing. Sixty isolates of S. aureus were tested; 28 (100%) of 28 isolates from patients with TSS but only five (16%) of 32 control isolates produced the toxin (P much less than 0.001). This protein exotoxin, which was purified by differential precipitation with ethanol and thin-layer isoelectric focusing, had an isoelectric point of 7.2. When tested by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the toxin migrated as a homogeneous protein with a molecular weight of 22,000. The exotoxin produced fever in rabbits and enhanced susceptibility to lethal shock caused by endotoxin. Other biologic properties of the exotoxin included lymphocyte mitogenicity and the capacity to suppress synthesis of IgM antibody to sheep erythrocytes.
641 citations
Cites background or methods from "A purified group a streptococcal py..."
...Pyrogenicity and the capacity to enhance host susceptibility to lethal shock and myocardial damage caused by endotoxin were measured as described by Kim and Watson [13]....
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...Not only was this exotoxin purified by techniques used previously to obtain pyrogenic exotoxins [6, 10], but the toxin thus purified, like the previously described exotoxins, demonstrated pyrogenicity, the capacity to enhance host susceptibility to lethal shock and myocardial and liver damage by endotoxin [6, 9, 13, 22], nonspecific mitogenicity with probable T-cell specificity [16, 23], and suppression of the IgM antibody response to sheep erythrocytes [14, 19, 20]....
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TL;DR: Risks Associated with Cloning Toxin Genes in Escherichia coli, and Recommended Containment Levels for Cloning, are discussed.
638 citations
TL;DR: Toxic-shock syndrome is an acute onset, multiorgan illness which resembles severe scarlet fever, caused by Staphylococcus aureus strains that express TSS toxin-1 (TSST-1), enterotoxins B, or enterotoxin C.
Abstract: Toxic-shock syndrome (TSS) is an acute onset, multiorgan illness which resembles severe scarlet fever. The illness is caused by Staphylococcus aureus strains that express TSS toxin-1 (TSST-1), enterotoxin B, or enterotoxin C. TSST-1 is associated with menstrual TSS and approximately one-half of nonmenstrual cases; the other two toxins cause nonmenstrual cases, 47% and 3%, respectively. The three toxins are expressed in culture media under similar environmental conditions. These conditions may explain the association of certain tampons with menstrual TSS. Biochemically, the toxins are all relatively low molecular weight and fairly heat and protease stable. Enterotoxins B and C, share nearly 50% sequence homology with streptococcal scarlet fever toxin A; they share no homology with TSST-1 despite sharing numerous biological properties. Numerous animal models for development of TSS have suggested mechanisms of toxin action, though the exact molecular action is not known. The toxins are all potent pyrogens, induce T lymphocyte proliferation, requiring interleukin 1 release from macrophages, suppress immunoglobulin production, enhance endotoxin shock, and enhance hypersensitivity skin reactions. The genetic control of the toxins has been studied and suggests the exotoxins are variable traits. Some additional properties of TSS S. aureus which facilitate disease causation have been clarified.
496 citations