Bacillus anthracis: Difference between revisions

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Capsule production depends on the pX02 plasmid (60 megadalton).
Capsule production depends on the pX02 plasmid (60 megadalton).  Capsule formation is important because it allows the organism to resist phagocytosis.





Revision as of 10:55, 1 May 2007

A Microbial Biorealm page on the genus Bacillus anthracis

Classification

Higher order taxa

cellular organisms; Bacteria (domain); Firmicutes (phylum); Bacilli (class); Bacillales (order); Bacillaceae (family); Bacillus (genus); Bacillus cereus group

Genus

Bacillus anthracis


NCBI: Taxonomy

Description and significance

Bacillus anthracis is a gram-positive, rod-shaped, aerobic bacterium, 1 - 1.2µm in width x 3 - 5µm in length. It lives in soils worldwide at mesophilic temperatures. It can be grown in aerobic or anaerobic conditons (facultative anaerobe) in medium with ordinary nutrients. The capsule (slime layer) is a polymer of amino acids (D-glutamate), unlike most other bacteria. A characteristic mucoid or "smooth" colony variant is correlated with capsule production ability. Virulent strains all form the capsule, and "rough" colony capsules are avirulent. Growth in atmospheric CO2 cause the antiphagoctic capsule and anthrax toxin proteins to be synthesized. The nontoxic capsule has an important role in infection establishment, while the end disease phases are mediated by the toxin. In 1877, this organism was the first to be shown to cause disease by Dr. Robert Koch and verified by Dr. Louis Pasteur. The organism was isolated from sick animals and grown in the laboratory to study endospore formation. It is similar to Bacillus cereus and Bacillus thuringiensis in cellular size, morphology, and spore formation.

When vegetative cells are deprived of certain nutrients, endospores are formed. Initially, the septum forms asymmetrically in the nutrient deprived cells that produce large (mother cell)and small (forespore) genome containing compartments. The forespore is engulfed by the mother cell and surrounded with three layers (cortex, coat, and exosporium), which are simultaneously formed. The thickest and innermost layer is the cortex. It is made up of peptidoglcan. The coat, consisting of a large number of different proteins, tightly covers the cortex. The exosporium is a loose-fitting, balloon-like structure that encloses the spore and serves as a souce of surface antigens. It is composed of an external hair-like nap and a paracrystalline basal layer. The hair-like nap has filaments that are mostly formed by a single collagen-like glycoprotein (called BclA), and the basal layer consists of a dozen different proteins. One of the proteins, BxpB (also called ExsF), is required for the attachment of the hair-like nap to the basal layer. Suppressing spore germination is another one of its roles. Large molecules that are a potential harm are excluded by the exosporium, which also serves as a semipermeable barrier.

The mother cell lyses and the spore is released when spore formation is finished. Spores can live in the soil environment and other inhospitable environments for many years because, once spores have matured, they are resistant to physical and chemical damage. They are highly resistant to heat, cold, dessication, radiation, and disinfectants. Spores germinate and grow as vegetative cells when they find an aqueous environment with the proper nutrients. Small-molecule germinants, including inosine and l-alanine, are recognized by spore receptors and activate germination. The receptors are found within the membrane of the spore that is under the cortex. Spores that enter a host germinate and grow, producing a fatal toxin.

Bacillus anthracis is an important molecule to study and genome sequence because its use as a biological weapon created concern. The interactions between the host's immune system cells and the spores are an important area of research that will give us a better understanding. Development of better spore detectors will also be helpful.

Other names for this organisms are Bacteridium anthracis and Bacillus cereus var. anthracis. Common names include "anthrax" and "anthrax bacterium."

Genome structure

Virulence factors are encoded on two plasmids, pXO1 (anthrax toxin) and pXO2 (capsule genes). The anthrax toxin consists of 3 components, a protective antigen (PA), lethal factor (LF), and edema factor (EF). PA/LF and PA/EF complexes are internalized by host cells where the LF (metalloprotease) and EF (calmodulin-dependent adenylate cyclase) components act. At high levels LF induces cell death and release of the bacterium while EF increases host susceptibility to infection and promotes fluid accumulation in the cells.


Capsule production depends on the pX02 plasmid (60 megadalton). Capsule formation is important because it allows the organism to resist phagocytosis.


Describe the size and content of the genome. How many chromosomes? Circular or linear? Other interesting features? What is known about its sequence?

Cell structure and metabolism

Describe any interesting features and/or cell structures; how it gains energy; what important molecules it produces.

Ecology

Describe any interactions with other organisms (included eukaryotes), contributions to the environment, effect on environment, etc.

Pathology

Bacillus anthracis causes the anthrax diesease, which represents a complex interaction between the host and parasite. The particles of anthrax that are infectious are the Bacillus anthracis endospores. The organism penetrates into the blood stream and harms the host by producing toxins within the body. The toxin is a complex of three plasmid-encoded proteins. Two of the proteins are directly toxic, including LF (lethal factor) and EF (edema factor). LF destroys white blood cells while EF increases cyclic AMP levels. Energy and water balance is impaired by the increase in cyclic AMP. The other plasmid-encoded protein, named PA (protective antigen), ushers the two toxic proteins in cells. PA forms a multimeric ring, which inserts into the cell membranes of the host. PA is not toxic alone, but if it is inactivated, the two toxic proteins would not cause harm. This is because PA allows the toxic components to pass through the membrane via a special toxin delivery system. The slimy capsule layer that surrounds Bacillus anthracis allows it to resist phagocytosis by white cells.

There common disease forms are cutaneous, pulmonary, and gastrointestinal. The cutaneous form is caused by handling contaminated materials, and the pulmonary form is caused by inhalation. Skin abrasions allow spores to enter and cause local lesions by germinating there and developing gelatinous edema. Patients with a cutaneous anthrax diesease mostly recover within 10 days, although a few progress to a life-threatening disease. Gastrointestinal anthrax is similar to cutaneous, but occuring on the intestinal mucosa. It is rare, but has an extremely high mortality rate. The pulmonary form of the disease results in a higher mortlity rate because the organism spreads through circulation. Macrophages in the lung's alveoli take up the spores and permit entry into the body. The infected macrophage lyses and bacteria is released into the blood stream, spreading though circulatory and lymphatic system. This results in septic shock, respiratory distress, and organ failure. Herbivorous animals become infected when they ingest spores from the soil. Experiments show that only about 3 x 106 cells/ml are needed to cause death in an animal. When humans contact infected animals (including flesh, bones, hides, hair and excrement), they become infected as well. Anthrax is almost never transmitted between people.

Until the 20th century, anthrax was a prevalent diesease in humans and cattle. It is still an important pathogen in some countries today. Some scholars believe that the Egyptian plagues in the Bible may have been caused by Anthrax. However, most people had not heard of anthrax until the recent 2001 scare in the United States. Robert Koch and Louis Pasteur developed a vaccine against anthrax, which was the first infectious disease they studied. The vaccines today are not fully effective. However, if the disease is diagnosed soon enough after infection, antibiotic treatment is effective. Methods to detect the organism quickly and new vaccines are under development. Because Bacillus anthracis lives in many soils, outbreaks are still reported. In fact, in the upper Midwest of the United States, many farms are under quarantine due to anthrax.

During the 20th century anthrax was used as a weapon in many countries. it has also been directed toward farm animals for warfare. The significance of anthrax as a terror weapon was realized in 2001. Although small outbreaks can result in a strong response, some people argue that anthrax is not an ideal biological weapon because the organism is not particularly pathogenic. To infect people, a large number of spores are needed. The most effective form of anthrax is a very fine powder. Therefore, to make anthrax a weapon, the preparation needs to be grinded into a fine powder. Anticaking agents are necessary as well to prevent clumping of the spores. Bacillus anthracis can be grown easily, but it is important to have special containment facilities and to be careful when working with them. They can be engineered to be resistant to antibiotics even though they are usually sensitive to antibiotics including penicillin and ciprofloxacin.

The incidence (1-2 cases of cutaneous disease per year) of naturally acquired anthrax is rare in the United States. In fall 2001, intentional contamination of mail resulted in 22 cases of anthrax, of which 11 were inhalation and 11 cutaneous.

How does this organism cause disease? Human, animal, plant hosts? Virulence factors, as well as patient symptoms.

Application to Biotechnology

Does this organism produce any useful compounds or enzymes? What are they and how are they used?

Current Research

Enter summaries of the most recent research here--at least three required

References

http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=1392&lvl=3&lin=f&keep=1&srchmode=1&unlock Wheeler DL, Chappey C, Lash AE, Leipe DD, Madden TL, Schuler GD, Tatusova TA, Rapp BA (2000). Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 2000 Jan 1;28(1):10-4 [PubMed]


http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1636282#r22 Jeremy A. Boydston, Ling Yue, John F. Kearney, and Charles L. Turnbough, Jr. "The ExsY Protein Is Required for Complete Formation of the Exosporium of Bacillus anthracis." J Bacteriol. 2006 November; 188(21): 7440–7448.


http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=303457 Hongbin Liu, Nicholas H. Bergman, Brendan Thomason, Shamira Shallom, Alyson Hazen, Joseph Crossno, David A. Rasko, Jacques Ravel, Timothy D. Read, Scott N. Peterson, John Yates III, and Philip C. Hanna. Formation and Composition of the Bacillus anthracis Endospore. J Bacteriol. 2004 January; 186(1): 164–178. doi: 10.1128/JB.186.1.164-178.2004.


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=10795 Entrez Genome Project


http://www.textbookofbacteriology.net/ Todar's Online Textbook of bacteriology.


Schaechter, M., J.L. Ingraham, F.C. Neidhardt. Microbe. (ASM Press, Washington, DC, 2006).


Edited by Grace Ucar, student of Rachel Larsen and Kit Pogliano