Anthrax is a disease caused by the bacterium Bacillus anthracis. It normally affects cattle, sheep, goats, etc.
It is acquired from spores that remain viable in the environment (e.g. soil) for decades always able to germinate into active bacteria if they get into the body of a susceptible host.
Humans can be infected by Bacillus anthracis, and if the spores enter by way of the lungs, the disease can be quickly fatal. These properties have made it one of the agents favored by bioterrorists.
It is not the tissue-destructiveness of the active bacteria that is the problem but rather the toxin that they secrete. (This is like the illnesses caused by the bacilli that cause diphtheria, tetanus, and botulism.) The bacteria are susceptible to antibiotics. Ciprofloxacin (Cipro®) is effective as are others such as doxycycline, but they must be given early before the toxin can produce symptoms.
Once the toxin is in the system, it can be neutralized by giving antitoxin antibodies (conferring so-called passive immunity). Presently these are harvested from donors who had received anthrax vaccine in the armed forces. But there is hope that monoclonal antibodies can be manufactured that will be able to provide protection.
The anthrax toxin is composed of three different proteins (encoded by genes on one of the two plasmids in the organism):
- PA ("protective antigen") It gets this name because it provides the epitopes that elicit protective antibodies in the anthrax vaccine.
- LF ("lethal factor")
- EF ("edema factor")
- PA molecules bind to receptors at the cell surface assembling in clusters of 7.
- LF and/or EF molecules then bind to these clusters.
- The complex is engulfed by receptor mediated endocytosis.
- The drop in pH in the endosome (endocytic vesicle) produces a change in the structure of the PA cluster enabling it to release its LF and EF into the cytosol.
- EF is an adenylyl cyclase which raises the intracellular concentration of cAMP inhibiting phagocytosis by neutrophils.
- As it name implies, LF in the cytosol so disturbs the machinery of the cell that it dies.
In April of 2001, John Collier and his colleagues reported that several mutant versions of PA protected rats from death by the active anthrax toxin.
The mutant molecules coassembled with normal PA molecules, and the complex was still able to bind LF and EF. However, the complex could not release LF or EF from the endosome, and the rats remained healthy.
Perhaps one of these altered PA molecules can be enlisted in the fight against bioterrorism as both:
- a vaccine to protect people before exposure and
- a treatment to block the lethal effects of the natural toxin after exposure.
Today's Anthrax Vaccine
The vaccine is made from an extract of a weakened strain of B. anthracis (it makes no surface capsule). The extract contains large amounts of PA, as well as some LF and EF.
Scores of different strains of anthrax have been isolated from many parts of the world. While they share most of their harmful traits, their genomes differ in the number of repeated sequences of noncoding DNA.
These are called VNTRs (for variable number of tandem repeats) and are simply longer versions of the short tandem repeats (STRs) now being used by law enforcement agencies for DNA fingerprinting of humans. [Link]
DNA fingerprinting of any strain of anthrax used by bioterrorists may help track down its source.
16 April 2014