Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.
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It is shown here that EF is an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1] produced by Bacillus anthracis in an inactive form and nearly equals that of the most active known cyclase.Abstract:
Anthrax toxin is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins individually cause no known physiological effects in animals but in pairs produce two toxic actions. Injection of PA with LF causes death of rats in 60 min, whereas PA with EF causes edema in the skin of rabbits and guinea pigs. The mechanisms of action of these proteins have not been determined. It is shown here that EF is an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] produced by Bacillus anthracis in an inactive form. Activation occurs upon contact with a heat-stable eukaryotic cell material. The specific activity of the resulting adenylate cyclase nearly equals that of the most active known cyclase. In Chinese hamster ovary cells exposed to PA and EF, cAMP concentrations increase without a lag to values about 200-fold above normal, remain high in the continued presence of toxin, and decrease rapidly after its removal. The increase in cAMP is completely blocked by excess LF. It is suggested that PA interacts with cells to form a receptor system by which EF and perhaps LF gain access to the cytoplasm.read more
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Proteolytic Inactivation of MAP-Kinase-Kinase by Anthrax Lethal Factor
Nicholas S. Duesbery,Craig P. Webb,Stephen H. Leppla,Valery M. Gordon,Kurt Klimpel,Terry D. Copeland,Natalie G. Ahn,M Oskarsson,Kenji Fukasawa,Ken D. Paull,George F. Vande Woude +10 more
TL;DR: It is shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway.
Journal ArticleDOI
Identification of the cellular receptor for anthrax toxin.
Kenneth A. Bradley,Jeremy Mogridge,Jeremy Mogridge,Michael Mourez,Robert J. Collier,John A. Young +5 more
TL;DR: The cloning of the human PA receptor is described using a genetic complementation approach and a soluble version of this domain can protect cells from the action of the toxin.
Journal ArticleDOI
Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin.
TL;DR: The recent elucidation of the three-dimensional structure of the heat-labile enterotoxin has provided an opportunity to examine and compare the correlations between structure and function of the two toxins, which may improve understanding of the disease process itself and illuminate the role of the toxin in studies of signal transduction and G-protein function.
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Anthrax toxin: receptor binding, internalization, pore formation, and translocation.
John A. T. Young,R. John Collier +1 more
TL;DR: Advances in understanding the entry process include insights into how PA recognizes its two known receptors and its ligands, LF and EF; how the PA:receptor interaction influences the pH-dependence of pore formation; and how the pore functions in promoting translocation of LF andEF across the endosomal membrane.
Journal ArticleDOI
Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process.
TL;DR: It is suggested that anthrax lethal toxin requires passage through an acidic endocytic vesicle in order to exert its toxic effect within the cytosol.
References
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Alterations in the biological activity of protective antigen of bacillus anthracis toxin.
TL;DR: Evidence is presented to show that protective antigen undergoes subtle alterations that affect its biological activity and, 4 hours following an injection of protective antigen, rats not only do not die when injected with lethal factor but also are protected from the lethal effect of whole toxin.
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Neurological and physiological responses of the primate to anthrax infection.
Frederick Klein,Ralph E. Lincoln,James P. Dobbs,Bill G. Mahlandt,Norman S. Remmele,Jerry S. Walker +5 more
TL;DR: The protective antigen component of the toxin alone caused the initial changes in surface cortical activity, and those animals that died showed a respiratory failure that appeared to be of central nervous system origin involving the respiratory center of the brain.
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Pathophysiologic Effects of Lethal and Immunoregulatory Doses of Cholera Enterotoxin in the Mouse
TL;DR: A sublethal dose known to have the capacity to modulate the immune response exerts a distinct stimulatory effect on cells in the splenic red pulp whereas cortical thymocytes are destroyed even at this lower dose.
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The use of an ultrasonic bath to disrupt cells suspended in volumes of less than 100 μliters
TL;DR: A procedure is described for the efficient disruption of small (10–100 μl) volumes of algal and bacterial cell suspensions and its applications in agriculture and materials science.
Journal ArticleDOI
Differential Cytotoxicity of Bacillus anthracis and Bacillus cereus Culture Filtrates.
TL;DR: The present communication describes a striking difference in cytotoxicity of B. cereus and B. anthracis culture filtrates incubated with various tissue-culture cell lines.