Anthrax – The Silent Killer

When you think of Anthrax you may think of a mediaeval disease that we found a prevention and treatment for a long time ago. Unfortunatley, the feared phrase “Biological Warfare” may also come to mind. But before we get on to that, let’s look at what Anthrax is…

The disease Anthrax is caused by the inhalation or ingestion of spores that are produced by the bacteria Bacillus anthracis. These spores, which can survive for a long time in harsh conditions without a host, can settle in 3 different places leading to 3 types of the disease: pulmonary (in the lungs), gastrointestinal (in the gut or intestines), or cutaneous (on the skin). These 3 types all have different symptoms, so the exact type of infection may not be initially obvious. To diagnose the disease a sample from the patient is taken and the bacteria is identified by a variety of methods such as gram staining the bacteria (B.anthracis is known to be gram positive) and immunosorbent assays to specifically detect the species. Once diagnosed the treatment must be administered quick sharp as the disease is often lethal once it has taken hold.

Once the spore has settled into a cosy place in its host (which is most commonly herbivorous grazing animals that can pass the disease onto humans) it begins to grow and release the disease causing toxin. The anthrax toxin is made of 3 protein components which have different functions. First the protective antigen (PA) binds to an anthrax toxin receptor on the surface of cells within the site of infection. This causes recruitment of other protective antigen monomers that form a heptameric (5 unit) ring that can bind up to 4 of either of the other 2 toxin components: Lethal Factor (LF) or Edema Factor (EF). This complex can then bud into the cell by endocytosis. This forms a vesicle within the cell in which the toxin subunits can assemble into the vesicle’s membrane. The hollow ring of PA subunits then releases the factors it is bound to into the cytoplasm of the target cell, which is triggered by a change in pH. This is where the LF and EF mediate disease.

anthrax

Protective Antigen (PA) binds to a surface receptor where it is cleaved by Furin into smaller components. This allows association with LF/EF, internalisation via vesicles, insertion into the vesicle membrane and release into the cytoplasm.

Once in the cellular cytoplasm, LF uses its endoprotease function to cleave the end from MAPKK, an essential signalling molecule in the cell. This abolishes the signalling pathways and leads to apoptosis (programmed cell death). Edema Factor acts as a adenylate cyclase which increases levels of cAMP in the cell which is involved in the activation of many signals. Vast increase of cAMP leads to a disruption of water homeostasis and the edema which is an accumulation of water under the skin. So it’s a pretty nasty disease and is still leading to deaths in the developing and developed world as the bacteria can survive in almost any condition on earth. If someone is infected, treatment must be initiated quickly to increase their chances of survival. The treatment currently used is antibiotics and monoclonal antibodies that can target the bacteria and neutralise the toxin.

There have been a number of anthrax outbreak threats in the past 10 years, and just like flu if a major outbreak does occur a vaccine will need to be on standby to immunise a large section of the public in that area. Many of the newly developed vaccines are based on injection of the PA subunit. When administered without the other factors, PA cannot cause disease and encourages an immune response for the body to form antibodies against it. These better equip the body to fight off the toxin if they do become infected with the real thing. To better increase the effectiveness of the vaccine changes can be made to increase its longevity when in storage and action when injected. The knowledge of protein folding and binding due to the known crystal structure has allowed fine tuning of the solution in which the PA subunit vaccine is held. Various experiments have identified the concentration of phosphate, the most effective dose, and other factors which will yield the largest response. An alhydrogel vaccine adjuvant is a suspension which weakly binds the PA to prevent aggregation and also is a strong inducer of the Th2 immune response, making a highly effective, fast acting vaccine that can be employed to the public if and when needed.

Anthrax spores were tested for its use in biological warfare before the ban of storage of biological weapons, however small groups still use anthrax spores in assassination attempts such as sending them in letters, so the knowledge that scientists have our back and have a effective vaccine on hold is very reassuring. Anthrax cases are still seen in isolated cases across the world, however the number is now very small and scientific knowledge of the disease and the toxin has allowed the development of a vaccine that is an outbreak should occur could save numerous lives.

Julia Rose

If you liked this article, you may also enjoy:

Starting small- Alzheimers evolutionary link to amyloid

Colicin N- A new target for antibiotics

The science behind Coeliac Disease

References

Chalton DA, Kelly IF, McGregor A, Ridley H, Watkinson A, Miller J, & Lakey JH (2007). Unfolding transitions of Bacillus anthracis protective antigen. Archives of biochemistry and biophysics, 465 (1), 1-10 PMID: 17531947

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s