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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Mapping the lethal factor and edema factor binding sites on oligomeric anthrax protective antigen
TL;DR: The results elucidate the process by which the components of anthrax toxin, and perhaps other binary bacterial toxins, assemble into toxic complexes by delineating a region within domain 1′ of PA that may represent the binding site for these ligands.
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Bacillus anthracis Edema Toxin Causes Extensive Tissue Lesions and Rapid Lethality in Mice
Aaron M. Firoved,Georgina F. Miller,Mahtab Moayeri,Rahul Kakkar,Yuequan Shen,Jason F. Wiggins,Elizabeth M. McNally,Wei-Jen Tang,Stephen H. Leppla +8 more
TL;DR: The first comprehensive study of ET-induced pathology in an animal model suggests that it causes death due to multiorgan failure and detail the extensive pathological lesions caused by ET.
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Fate of germinated Bacillus anthracis spores in primary murine macrophages
TL;DR: The data strongly suggest that the B. anthracis toxinogenic, unencapsulated Sterne strain (7702) does not multiply within macrophages and this results contributed to reveal the strategies used by B. Anthracis to survive within the host and to reach the external medium where they proliferate.
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Defining a serological correlate of protection in rabbits for a recombinant anthrax vaccine.
Stephen F. Little,Bruce E. Ivins,P.F. Fellows,Margaret L. Pitt,Sarah L. Norris,Gerard P. Andrews +5 more
TL;DR: Results suggested that the antibody response, as determined by the quantitative anti-rPA IgG ELISA and toxin neutralizing antibody (TNA) assay, were significant predictors of protection against a B. anthracis aerosol spore challenge in rabbits.
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A deleted variant of Bacillus anthracis protective antigen is non-toxic and blocks anthrax toxin action in vivo.
Yogendra Singh,Yogendra Singh,Vijay K. Chaudhary,Vijay K. Chaudhary,Stephen H. Leppla,Stephen H. Leppla,Stephen H. Leppla +6 more
TL;DR: Deleted PA is expected to have normal immunogenicity, but would not combine with trace amounts of LF and EF to cause toxicity and be useful as a replacement for the PA that is the major active ingredient in the current human anthrax vaccine.
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