Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.
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TLDR
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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Anthrax toxins: a paradigm of bacterial immune suppression
TL;DR: B. anthracis can invade the host, with ensuing massive bacteremia and toxemia, and the specific effects of B. Anthracis on neutrophils, macrophages, dendritic cells, T- and B-lymphocytes are reviewed.
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Cloning and characterization of a gene whose product is a trans-activator of anthrax toxin synthesis.
TL;DR: Results demonstrate that the atxA product activates not only transcription of pag but also that of cya and lef, and plays a role in the induction of anthrax toxin gene expression by bicarbonate.
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Cloning of the protective antigen gene of Bacillus anthracis
TL;DR: Recombinant plasmids containing the PA gene have been isolated in the E. coli vector pBR322 from Bam HI-generated fragments of the anthrax plasmid, pBA1.
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Inhalational Anthrax: Epidemiology, Diagnosis, and Management
TL;DR: The course of inhalational anthrax is dramatic, from the insidious onset of nonspecific influenza-like symptoms to severe dyspnea, hypotension, and hemorrhage within days of exposure, culminating in septic shock, respiratory distress, and death within 24 h.
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Identification of small molecule inhibitors of anthrax lethal factor
Rekha G. Panchal,Ann R. Hermone,Tam Luong Nguyen,Thiang Yian Wong,Robert Schwarzenbacher,James J. Schmidt,Douglas Lane,Connor F. McGrath,Benjamin E. Turk,James C. Burnett,M. Javad Aman,Stephen F. Little,Edward A. Sausville,Daniel W. Zaharevitz,Lewis C. Cantley,Robert C. Liddington,Rick Gussio,Sina Bavari +17 more
TL;DR: Six inhibitors of LF are described on the basis of a pharmacophoric relationship determined using X-ray crystallographic data, molecular docking studies and three-dimensional (3D) database mining from the US National Cancer Institute (NCI) chemical repository.
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