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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Rapid generation of an anthrax immunotherapeutic from goats using a novel non-toxic muramyl dipeptide adjuvant
Cassandra D Kelly,Chris O'Loughlin,Frank B. Gelder,Johnny W. Peterson,Laurie E. Sower,Nick M Cirino +5 more
TL;DR: The protection afforded by these GMP-grade caprine immunotherapeutics post-exposure in the pilot murine model suggests they could be used effectively to treat post-Exposure, symptomatic human anthrax patients following a bioterrorism event.
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Vaccines produced by conventional means to control major infectious diseases of man and animals.
James L. Bittle,Susie Muir +1 more
TL;DR: This chapter reviews the development of some of vaccines and their use in controlling such major diseases as diphtheria, rinderpest, Newcastle disease, smallpox, pertussis, yellow fever, rabies, etc.
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Catalytically inactive anthrax toxin(s) are potential prophylactic agents.
TL;DR: The present study found that the catalytic mutants of LF (LFE687A) and EF (EFH351A) competitively inhibited lethal toxin and edema toxin-mediated activity in vitro and lethality in vivo and were non-toxic to sensitive cell lines when combined with PA.
Journal ArticleDOI
Anthrax edema toxin inhibits Nox1-mediated formation of reactive oxygen species by colon epithelial cells
Jun-Sub Kim,Gary M. Bokoch +1 more
TL;DR: It is shown that ETx effectively inhibits ROS formation by Nox1 in HT-29 colon epithelial cells, and may be a mechanism used by B. anthracis to circumvent the innate immune response.
Journal ArticleDOI
T cell targeting by anthrax toxins: two faces of the same coin.
TL;DR: How B. anthracis uses LT and ET to suppress the immune defenses of the host, focusing on T lymphocytes, the key players in adaptive immunity is discussed, and recent findings showing that ET has the ability not only to suppress T cell activation but also to promote the polarization of CD4+ T cells to the Th2 and Th17 subsets are summarized.
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