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Progress and novel strategies in vaccine development and treatment of anthrax

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TLDR
Although anthrax is acknowledged as a toxinogenic disease, additional factors, other than the bacterial toxin, may be involved in the virulence of B. anthracis and may be needed for the long‐lasting protection conferred by PA immunization.
Abstract
The lethal anthrax disease is caused by spores of the gram-positive Bacillus anthracis, a member of the cereus group of bacilli. Although the disease is very rare in the Western world, development of anthrax countermeasures gains increasing attention due to the potential use of B. anthracis spores as a bio-terror weapon. Protective antigen (PA), the non-toxic subunit of the bacterial secreted exotoxin, fulfills the role of recognizing a specific receptor and mediating the entry of the toxin into the host target cells. PA elicits a protective immune response and represents the basis for all current anthrax vaccines. Anti-PA neutralizing antibodies are useful correlates for protection and for vaccine efficacy evaluation. Post exposure anti-toxemic and anti-bacteremic prophylactic treatment of anthrax requires prolonged antibiotic administration. Shorter efficient postexposure treatments may require active or passive immunization, in addition to antibiotics. Although anthrax is acknowledged as a toxinogenic disease, additional factors, other than the bacterial toxin, may be involved in the virulence of B. anthracis and may be needed for the long-lasting protection conferred by PA immunization. The search for such novel factors is the focus of several high throughput genomic and proteomic studies that are already leading to identification of novel targets for therapeutics, for vaccine candidates, as well as biomarkers for detection and diagnosis.

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Citations
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Mechanisms of biocontrol and plant growth-promoting activity in soil bacterial species of Bacillus and Pseudomonas: a review

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Synthetic carbohydrate-based vaccines: challenges and opportunities

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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.
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Identification of the cellular receptor for anthrax toxin.

TL;DR: The cloning of the human PA receptor is described using a genetic complementation approach and a soluble version of this domain can protect cells from the action of the toxin.
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The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria

TL;DR: Several chromosomally encoded proteins that may contribute to pathogenicity—including haemolysins, phospholipases and iron acquisition functions—and numerous surface proteins that might be important targets for vaccines and drugs are found.
Journal ArticleDOI

Genomics of the Bacillus cereus group of organisms

TL;DR: This group of organisms represents microbes of high economic, medical and biodefense importance and contains the highest number of closely related fully sequenced genomes, giving the unique opportunity for thorough comparative genomic analyses.
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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