RAPID LETHAL EFFECT IN RATS OF A THIRD COMPONENT FOUND UPON FRACTIONATING THE TOXIN OF
            <i>BACILLUS ANTHRACIS</i>

Beall, Francis A.; Taylor, Martha J.; Thorne, Curtis B.

doi:10.1128/jb.83.6.1274-1280.1962

Cited by 193 publications

(76 citation statements)

References 6 publications

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“…toxicity (Beall et al, 1962;Haines et al, 1965). Studies have suggested that LeTx induces hypotensive shock in rats by depressing cardiac ventricular activity (Watson et al, 2007;Kuo et al, 2008).…”

Section: Immunology and Medical Microbiologymentioning

confidence: 99%

Monoclonal antibodies directed against protective antigen ofBacillus anthracisenhance lethal toxin activityin vivo

Little

Webster

Fisher

2011

FEMS Immunol Med Microbiol

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Protective antigen (PA) from Bacillus anthracis binds to cellular receptors, combines with lethal factor (LF) forming lethal toxin (LeTx), and facilitates the translocation of LF into the cytosol. LeTx is cytotoxic for J774A.1 cells, a murine macrophage cell line, and causes death of Fisher 344 rats when injected intravenously. PA is also the major protective component in anthrax vaccines. Antibody-dependent enhancement has been reported for several viral diseases, a bacterial infection, and for B. anthracis LeTx in vitro cytotoxicity. Further screening of our 73 PA monoclonal antibodies (mAbs) identified a total of 17 PA mAbs that enhanced in vitro cytotoxicity at suboptimal concentrations of LeTx. A competitive binding enzyme-linked immunosorbent assay showed that these 17 PA mAbs identified eight different antigenic regions on PA. Eight of the 17 PA mAbs that enhanced LeTx in vitro cytoxicity were examined for their activity in vivo. Of the eight mAbs that were injected intravenously with a sublethal concentration of LeTx into male Fisher 344 rats, four mAbs enhanced the lethality of LeTx and resulted in the death of animals, whereas control animals did not succumb to intoxication. This is the first demonstration that PA mAbs can enhance LeTx intoxication in vivo.

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Section: Immunology and Medical Microbiologymentioning

confidence: 99%

Monoclonal antibodies directed against protective antigen ofBacillus anthracisenhance lethal toxin activityin vivo

Little

Webster

Fisher

2011

FEMS Immunol Med Microbiol

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“…These three factors are the protective antigen (PA), the lethal factor (LF) and the oedema factor (EF). Intravenous injections of PA + LF (lethal toxin, LT) have been shown to be lethal (Beall et al, 1962). Intradermal injections of PA + EF (or oedema toxin, ET) induce oedema in the skin (Stanley and Smith, 1961), and may also be lethal.…”

Section: The Molecular Characterization Of Lethal and Oedema Toxin Efmentioning

confidence: 99%

Contribution of toxins to the pathogenesis of inhalational anthrax

Tournier¹,

Quesnel‐Hellmann²,

Cleret³

et al. 2007

Cell Microbiol

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SummaryInhalational anthrax is a life-threatening infectious disease of considerable concern, especially as a potential bioterrorism agent. Progress is gradually being made towards understanding the mechanisms used by Bacillus anthracis to escape the immune system and to induce severe septicaemia associated with toxaemia and leading to death. Recent advances in fundamental research have revealed previously unsuspected roles for toxins in various cell types. We summarize here pathological data for animal models and macroscopic histological examination data from recent clinical records, which we link to the effects of toxins. We describe three major steps in infection: (i) an invasion phase in the lung, during which toxins have short-distance effects on lung phagocytes; (ii) a phase of bacillus proliferation in the mediastinal lymph nodes, with local effects of toxins; and (iii) a terminal, diffusion phase, characterized by a high blood bacterial load and by long-distance effects of toxins, leading to host death. The pathophysiology of inhalational anthrax thus involves interactions between toxins and various cell partners, throughout the course of infection.

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“…Alternatively, LT may cripple MDDC activity without overt cytotoxicity (Kassam et al, 2005;Tournier et al, 2005). LT contributes significantly to virulence and injection of purified LT induces shock and death in animals (Beall et al, 1962;Pezard et al, 1991). As a result, LT has received more attention than OT experimentally.…”

Section: Introductionmentioning

confidence: 99%

Anthrax oedema toxin induces anthrax toxin receptor expression in monocyte‐derived cells

Maldonado-Arocho

Fulcher

Lee

et al. 2006

Molecular Microbiology

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SummaryBacillus anthracis, the causative agent of anthrax, secretes two bipartite toxins that help the bacterium evade the immune system and contribute directly to pathogenesis. Both toxin catalytic moieties, lethal factor (LF) and oedema factor (OF), are internalized into the host-cell cytosol by a third factor, protective antigen (PA), which binds to cellular anthrax toxin receptors (ANTXRs). Oedema factor is an adenylate cyclase that impairs host defences by raising cellular cAMP levels. Here we demonstrate that oedema toxin (PA + OF) induces an increase in ANTXR expression levels in macrophages and dendritic cells resulting in an increased rate of toxin internalization. Furthermore, we show that increases in ANTXR mRNA levels depends on the ability of OF to increase cAMP levels, is mediated through protein kinase A-directed signalling and is monocyte-lineage-specific. To our knowledge, this is the first report of a bacterial toxin inducing host target cells to increase toxin receptor expression.

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RAPID LETHAL EFFECT IN RATS OF A THIRD COMPONENT FOUND UPON FRACTIONATING THE TOXIN OF BACILLUS ANTHRACIS

Cited by 193 publications

References 6 publications

Monoclonal antibodies directed against protective antigen ofBacillus anthracisenhance lethal toxin activityin vivo

Monoclonal antibodies directed against protective antigen ofBacillus anthracisenhance lethal toxin activityin vivo

Contribution of toxins to the pathogenesis of inhalational anthrax

Anthrax oedema toxin induces anthrax toxin receptor expression in monocyte‐derived cells

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