Focus on anthrax
Recent events have confirmed that bioterrorism is no longer a threat but a reality. To provide wide-ranging access to the latest scientific information about anthrax and other potential bioweapons, Nature has put together a special online focus on this issue. This focus is made up of two research papers on anthrax toxin, as well as a collection of research, news and feature articles from our electronic archive.
The causative agent of the anthrax disease, the bacterium Bacillus anthracis, secretes a toxin made up of three proteins: protective antigen (PA), oedema factor (OF) and lethal factor (LF). PA binds to cell-surface receptors on the host's cell membranes. After being cleaved by a protease, PA binds to the two toxic enzymes, OF and LA, and mediates their transportation into the cytosol where they exert their pathogenic effects.
In addition to these Nature papers, this special focus also includes research from October's issue of Nature Biotechnology. Mourez et al. describe the isolation of a synthetic peptide that blocks the action of anthrax toxin in an animal model. These research papers are complimented by a news feature which looks at the threat of bioterrorism and researchers' attempts to counter it, and a collection of research, news and opinion articles from our archive.
Nature's news and science-writing teams will continue to inform and explain the science behind current events as and when it happens, and this page will be updated accordingly.
Anthrax poses a significant threat as an agent of biological warfare and terrorism. Inhalational anthrax, in which spores of Bacillus anthracis are inhaled, is almost always fatal, as diagnosis is rarely possible before the disease has progressed to a point where antibiotic treatment is ineffective. The major virulence factors of B. anthracis are a poly-d-glutamic acid capsule and anthrax toxin. Anthrax toxin consists of three distinct proteins that act in concert: two enzymes, LF and oedema factor (an adenylate cyclase); and PA. The PA is a four-domain protei that binds a host cell-surface receptor by its carboxy-terminal domain; cleavage of its N-terminal domain by a furin-like protease allows PA to form heptamers that bind the toxic enzymes with high affinity through homologous N-terminal domains. The complex is endocytosed; acidification of the endosome leads to membrane insertion of the PA heptamer by forming a 14-stranded 
The MAPKK family of proteins are the only known cellular substrates of LF. Cleavage by LF near to their N termini removes the docking sequence for the downstream cognate MAP kinase. The effect of lethal toxin on tumour cells, for example, is to inhibit tumour growth and angiogenesis, most probably by inhibiting the MAPKK-1 and MAPKK-2 pathways. However, the primary cell type affected in anthrax pathogenesis is the macrophage. Here, recent evidence shows that low levels of lethal toxin cleave MAPKK-3, inhibiting release, but not production, of the pro-inflammatory mediators, NO and tumour necrosis factor-
We solved the structure of LF in two crystal forms with very different packing environments. Nevertheless, differences in tertiary and quaternary structure are small, and the better diffracting crystal form has been refined to 2.2 Å resolution. The molecule is 100 Å tall and 70 Å wide at its base, with domain I perched on top of the other three domains, which are intimately connected and probably comprise a single folding unit. The only contacts between domain I and the rest of the molecule are with domain II, and these chiefly involve charged polar and water-mediated interactions. The nature of the interface is consistent with the ability of a recombinant N-terminal fragment (residues 1–254) to be expressed as a soluble folded domain that maintains the ability to bind PA and enables the translocation of heterologous fusion proteins into the cytoso
