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the web of life in southern Africa

Bacillus anthracis (causes the disease anthrax)

Life > Eubacteria > Phylum: Firmicutes > Class: "Bacilli" > Order: Bacillales > Family: Bacillaceae

 

Bacillus species form resistant spores that last for ages

Bacillus species are rod-shaped bacteria that are able to turn into resistant spores when conditions get tough (such as when the host dies). Only one spore is formed from each cell. Spores are highly resistant to environmental extremes and can survive in natural environments for decades, being mainly found in the soil. As a result it is impossible to eradicate anthrax from regions where it has had a long history of infecting animals.

Anthrax is a disease mainly of herbivorous mammals

Herbivorous animals become infected with Bacillus anthracis by ingesting spores on forage plants. The spores can end up on the plants by being blown in dust from the soil or can be deposited on leaves by flies that have been feeding on anthrax-infected carcasses. The primary route of infection for herbivorous animals is therefore via the gut. 

There are 3 main ways people can become infected 

  • Through the skin (cutaneous). More than 95% of anthrax cases worldwide are caused by cutaneous infection. Infection typically occurs through people such as farmers, veterinarians, knackers and butchers, handling infected animals or animal products. The spores enter through cuts or abrasions in the skin. After 2-3 days a small pimple appears at the site of infection which steadily grows over the next few days into an ulcer with a central region of black, dead tissue (called an eschar). The ulcer is not painful unless there is a secondary infection, and there is a build up of fluid in the tissues around it (i.e. an edema).  In most cases the disease remains limited to the initial site of infection and eventually disappears because of the immune defenses fighting back. However, about 20 percent of untreated cases end up in death, caused by the bacterium and its toxins getting into the blood stream (i.e. septicemia). 
  • Through the gut (intestinal). People can become infected with the anthrax bacillus via the gut through eating under-cooked meat from infected animals. Infection occurs by the bacterium entering the lining of the intestine through a pre-existing wound and results in inflammation of the intestine. The bacterium then spreads from the lining of the intestine to the lymphatic system. A person infected through this intestinal route experiences feelings of nausea, loss of appetite, vomiting and fever followed by abdominal pain, vomiting of blood, and severe diarrhea. Death occurs in 25% to 65% of cases of intestinal infection.
  • Through the lungs (pulmonary). Infection occurs here through breathing in of spores. Conventionally, people handling animal products such as hides and wool, are susceptible to this form of infection because they are likely to breath in spore-laden dust. It is for this reason that pulmonary anthrax is commonly called wool-sorter's disease (with the current bioterrorism attacks through the mail, mailsorter's disease might be a more appropriate term).

Death is caused by the toxins that Bacillus anthracis produces

Bacillus anthracis cells contain plasmids (independent circles of DNA, not part of the main genome) that produce a toxin consisting of three different proteins.

 

Glossary
  • edema (or oedema). accumulation of fluids in tissue spaces
  • macrophages and neutrophils. Two types of lymphocyte (white blood cells) that phagocytose or 'eat up' invading microorganisms.
  • ATP. Adenosine 5'-triphosphate. Stores chemical energy in the cell. 
  • Edema factor (EF). This protein is an enzyme that elevates cyclic AMP in cells which in turn affects cell membrane permeability, which is thought to result in loss of fluid from the cells, causing edema in the host. The other effect of EF is to get into macrophages and neutrophils and lower their ATP reserves to the extent that their ability to consume invading microorganisms is reduced.
  • Lethal factor (LF). It is not certain how LF operates but it is basically an enzyme that affects chemical processes in the host cell to the extent that the cell dies.
  • Protective antigen (PA). PA is not toxic by itself but it is essential in opening the way for EF and LF to have a toxic effect because it enables them to enter into host cells. PA is able to bind to specific receptors on the host cell surface and in the process it creates a binding site for either EF or LF. The complex (either PA+LF or PA+EF) is then taken into the cell. See under treatments, below, for information on a newly developed substance that seems to be able to block the binding of EF or LF with PA.

Treatments available for anthrax

  • Vaccinations are available for animals and people, but the ones for people are generally reserved for those at high risk such as those that work with animals and animal products such as skins. The US military has been vaccinating its forces to counteract biological warfare.
  • Antibiotics are effective in killing Bacillus anthracis but need to be given early on in the infection before the bacillus has produced lethal amounts of toxin.
  • Mourez et al. have recently developed a polyvalent inhibitor (PVI) that stops the two toxic enzymes (EF and LF) produced by B. anthracis from combining with the protective antigen (PA) on the host cell surface thus preventing them from entering the host cell. This substance has been tested successfully on rats but it is not yet available for human use (see Nature Biotechnology 19: 958, October 2001, and a report on this paper in Nature 413: xi, October 2001)

Why anthrax is a favoured organism in biological warfare

  • Unless treated early on with antibiotics (before large amounts of toxins are produced), it kills people.
  • Large numbers of spores can be produced in the laboratory.
  • Spores can survive for decades in storage.
  • Missiles, bombs, letters, etc can all be used to distribute the spores.

Names for the disease anthrax

The name 'anthrax' is derived from the Greek word for coal. In medieval times, anthrax was known as black bane. The association of the colour black with anthrax is probably because the ulcer in the skin caused by cutaneous anthrax often has a black central portion of dead tissue. Anthrax is also known in English as wool-sorter's disease because people sorting wool are particularly susceptible to the pulmonary form of infection by anthrax (see above).

In Afrikaans, anthrax is known as miltsiekte, meaning spleen sickness. The spleen the main battle ground in the body where the white blood cells attack invading organisms in the blood. Anthrax toxins become concentrated in the regional lymph nodes and spleen and cause breakdown of the spleen.

History of the disease

  • Anthrax has affected humans throughout recorded history. The 5th and 6th plagues of Egypt that are described in the book of Exodus are thought to have been anthrax. 
  • Bacillus anthracis is famous in the history of bacteriology because it was the first bacterium that was shown to cause a disease. Through a series of rigorous experiments, the German physician Robert Koch (born 1843, died 1910) discovered the link between this bacterium and the disease anthrax and published his findings in 1876 (As an aside, it is interesting to note that Robert Koch worked in Kimberley, South Africa from 1896-97 developing a vaccine against rinderpest. From 1903-1904 he also investigated an outbreak of East Coast Fever in what was Rhodesia, now Zimbabwe).
  • Louis Pasteur (born 1822, died 1895) and his co-workers independently discovered the link between the bacterium and the disease and also found that the spores in dead animals that had died of anthrax survived after the animals had been buried, and were brought to the surface by earthworms
  • An effective animal vaccine was developed in the 1930's by M. Sterne at the Veterinary Research Institute, Onderstepoort, South Africa. 
  • Only in 1954 was it realised that B. anthracis produces toxins and that these are the main reason the host feels sick or dies.
  • An effective human vaccine was developed in the mid-1960's.

Links

References

  • Prescott, L.M, Harley, J.P. & Klein, D.A. 1999. Microbiology. 4th edition. McGraw-Hill, Boston.

Text by Hamish Robertson