Archives for December 2009

Anthrax is an illness caused by the bacterium bacillus anthracis. The bacteria are spread through spores and can infect the host cutaneously, inhalationally, or gastrointestinally. If infected, anthrax can often be fatal to the host. The bacteria employ a synergistic binary mechanism in order to infect eukaryotic cells and inflict the host with the illness. The symbiotic nature of anthrax is what makes it especially potent and of such concern.

The basic binary mechanism works with two components; component “A” and component “B.” Precursor component B must first be activated via proteolysis to form an oligomer. These activated B components will either then form a heptamer in solution which will then bind to a receptor on the cell surface, or bind as monomers to the receptor and form a homoheptamer. This component B-receptor complex then acts as a docking station for component A. Under acidic conditions, enzymatic component A is able to be translocated through the component B-receptor complex into the cytosol.

Once in the cytosol, component A is able to then disarm the cell through a number of different methods. First, component A could potentially force mono-ADP-ribosylation of G-actin, which incites cytoskeletal disarry and cell death. Second, it could induce proteolysis of mitogen-activated protein kinase kinases (MAPKK), which prevents cell signaling. Finally, component A could increase cellular levels of cyclic AMP, which results in immunosuppression and edema.

Anthrax consists of three synergistically acting proteins. The first protein of interest is the protective antigen (PA), which serves as the component B. It can be activated proteolytically from PA83 to PA63 via either trypsin, serum, of furin. It should be noted that furin is a special case, in which PA83 binds to the receptor before being activated by furin located on the cell surface. Once the heptamer of PA63 is formed, it is then able to send the A components into the cytosol under acidic conditions.

In the case of anthrax, component A actually consists of two separate proteins; the lethal factor (LF) and edema factor (EF). These two factors compete for docking rights on the PA63 heptamer in order to gain entrance into the cytosol. When the factors come into with the PA, they react to form lethal toxin and edema toxin. Upon entering the cytosol, each toxin does slightly different destruction on the cell.

Lethal toxin disarms the host immune system. It does this by targeting macrophages and dendritic cells, which eliminates any immunological response that the hosts would have. In essence, the host becomes deprived on pathogen killing cells. The edema toxin works in conjunction with the lethal factor by increasing cellular levels of cyclic AMP. This decreases the host immune response. The combination of these two toxins leads to a build up of bacteria and the host cannot attack the infection because its immune system is nearly non-existent thanks to anthrax.

Anthrax infection can be prevented by vaccine and treated with antibiotics. It was of national concern during the fall of 2001 when anthrax was found in the mail. This made people weary of anthrax as a possible biological weapon that could be used for terrorism. It can be made in vitro, which is part of what makes it such a threat. Anthrax spores can be destroyed with formaldehyde. The name anthrax comes from a Greek word for “coal,” which refers to the black ulcers that form from cutaneous infections. In all, anthrax can be a deadly disease and needs to be carefully dealt with.

Bibliography

Barth H, Aktories K, Popoff MR, Stiles BG. “Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins.” Microbiol Mol Biol Rev. 2004 Sep;68(3):373-402, table of contents. Review.

Guarner J, Zaki SR. “Histopathology and immunohistochemistry in the diagnosis of bioterrorism agents.” J Histochem Cytochem. 2006 Jan;54(1):3-11. Epub 2005 Sep 7.

Otherwise known as: “A Reusable Polymeric Asymmetric Hydrogenation Catalyst Made by Ring-Opening Olfein Metathesis Polymerization”

This was a PowerPoint presentation I did for class.