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Journal ArticleDOI

Differences in susceptibility of inbred mice to Bacillus anthracis.

Susan L. Welkos, +2 more
- 01 Mar 1986 - 
- Vol. 51, Iss: 3, pp 795-800
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TLDR
The mouse model appears to be useful in studies on host resistance to anthrax and on the pathogenesis of the infection, especially when studies suggested that resistance to the Sterne strain is determined by a single dominant gene or gene complex.
Abstract
Animal species differ in their resistance both to infection by Bacillus anthracis and to anthrax toxin. A mouse model was developed to study the basis of the host differences and the pathogenesis of infection. When mice were infected with the virulent B. anthracis strain Vollum 1B, low 50% lethal dose (LD50) values (5 to 30 spores) were found for all 10 strains of inbred mice tested. However, analysis of time-to-death data revealed significant differences among the strains, which could be divided into three groups: most susceptible (A/J and DBA/2J); least susceptible (CBA/J, BALB/cJ, and C57BR/cdJ); and intermediate (the remaining five strains). In contrast, the mice were distinctly susceptible or resistant to lethal infection by the toxigenic, nonencapsulated Sterne vaccine strain. The LD50 for the susceptible A/J and DBA/2J mice was approximately 10(3) spores of the Sterne strain, whereas the remaining eight relatively resistant strains were killed only by 10(6) or more spores. F1 hybrid and backcross studies suggested that resistance to the Sterne strain is determined by a single dominant gene or gene complex. Mice lethally infected with B. anthracis showed an acute course of infection, characterized by extensive gelatinous edema and large concentrations of bacilli in the blood and organs (e.g., 10(9) CFU/g of spleen). The susceptibility of A/J and CBA/J mice to intravenously injected anthrax toxin components appeared to differ from their susceptibility to infection. The toxin LD50 values for both strains were similar. However, CBA/J mice died sooner than did A/J mice, with mean time to death of 0.9 and 3.7 days, respectively, in mice given 4 LD50 of toxin. The mouse model appears to be useful in studies on host resistance to anthrax and on the pathogenesis of the infection.

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Anti-TNF-alpha therapies: the next generation

TL;DR: This review discusses briefly the present understanding of TNF-α-mediated biology and the current injectable therapies in clinical use, and focuses on some of the new therapeutic approaches with oral, small-molecule inhibitors.
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Macrophage Apoptosis by Anthrax Lethal Factor Through p38 MAP Kinase Inhibition

TL;DR: It is found that B. anthracis lethal factor selectively induces apoptosis of activated macrophages by cleaving the amino-terminal extension of mitogen-activated protein kinase (MAPK) kinases (MKKs) that activate p38 MAPKs.
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Contribution of individual toxin components to virulence of Bacillus anthracis.

TL;DR: The results suggest that the three toxin components might act synergistically in vivo to cause lethality and edema formation.
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Anthrax vaccines: past, present and future.

TL;DR: Most livestock vaccines in use throughout the world today for immunization against anthrax are derivatives of the live spore vaccine formulated by Sterne in 1937 and still use descendants of his strain 34F2, and room for development of a successor is discussed.
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Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNγ‐induced release of NO and TNFα

TL;DR: The first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor‐α induced by lipopolysaccharide/interferonγ is presented.
References
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Journal ArticleDOI

Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.

TL;DR: 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.
Journal ArticleDOI

Demonstration of a capsule plasmid in Bacillus anthracis.

TL;DR: Proof that pXO2 is involved in capsule synthesis came from experiments in which the plasmid was transferred by CP-51-mediated transduction and by a mating system in which plasmids transfer is mediated by a Bacillus thuringiensis fertility plasmide, pXo12.
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