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Encyclopedia of Genetics, Rev. Ed. Anthrax Field of Study: Bacterial genetics Significance: Anthrax has plagued humankind for thousands of years. Naturally occurring anthrax spores have caused disease in livestock and wildlife more often than in humans, but with the rise of genetic technologies anthrax became amenable to manipulation as an agent of bioterrorism and biowarfare. Key Terms PLASMIDS: extrachromosomal DNA, found most commonly in bacteria, which can be transferred between bacterial cells POLYMERASE CHAIN REACTION (PCR): a process in which a portion of DNA is selected and repeatedly replicated SINGLE NUCLEOTIDE POLYMORPHISM (SNP): the difference in a single nucleotide between the DNA of individual organisms VARIABLE NUMBER TANDEM REPEAT (VNTR): the difference in the number of tandem repeats (short sequences of DNA repeated over and over) between the DNA of individual organisms History A disease killing cattle in 1491 B.C.E., likely to have been anthrax, is recounted in the Book of Genesis. In Exodus 9, the Lord instructs Moses to take "handfuls of ashes of the furnace" and "sprinkle it toward the heaven in the sight of the Pharaoh." Moses performed the deed and "it became a boil breaking forth with blains upon man and upon beast." This may represent the first use of anthrax as a biological agent. Greek peasants tending goats suffered from anthrax; the Greek word from which "anthrax" derives means coal, referring to the coal-black center of the skin lesion. Anthrax became the first pathogenic bacillus to be seen microscopically when described in infected animal tissue by Aloys-Antoine Pollender in 1849. Studies by Robert Koch in 1876 resulted in the four postulates that form the basis for the study of infectious disease causation. In 1881, Louis Pasteur demonstrated the protective efficacy of a vaccine for sheep made with his attenuated vaccine strain. The Disease Anthrax is primarily a disease of herbivorous animals that can spread to humans through association with domesticated animals and their products. Herbivorous animals grazing in pastures with soil contaminated with anthrax endospores become infected when the spores gain entry through abrasions around the mouth and germinate in the surrounding tissues. Omnivores and carnivores can become infected by ingesting contaminated meat. Human infection is often a result of a close association with herbivores, particularly goats, sheep, or cattle (including their products of hair, wool, and hides). The most common clinical illness in humans is skin infection, acquired when spores penetrate through cuts or abrasions. After an incubation period of three to five days, a papule develops, evolves into a vesicle, and ruptures, leaving an ulcer that dries to form the characteristic black scab. Inhaled spores reach the alveoli of the lung, where they are engulfed by macrophages and germinate into bacilli. Bacilli are carried to lymph nodes, where release and multiplication are followed by bloodstream invasion and the infection's spread to other parts of the body, including the brain, where it causes meningitis. The symptoms of the illness, which begin a few days after inhalation, resemble those of the flu and may be associated with substernal discomfort. Cough, fever, chills, and respiratory distress with raspy, labored breathing ensue. The least common type of infection is that of the gastrointestinal tract. An effective vaccine is available for prevention, and antibiotics have been used when immediate protection is needed. Antibiotics can also successfully treat the infection. Inhalational anthrax is nearly always fatal if untreated, and even with treatment the mortality ranges from 40 to 80 percent. Mortality from treated cutaneous anthrax is less than 1 percent. The Anthrax Bacterium The Bacillus anthracis bacterium is large (1-1.2 × 3-10 microns), encapsulated, Gram-positive, and rod-shaped. It produces spores and exotoxins (toxins that are released from the cells). Spores are ellipsoidal or oval (1-2 microns) and located within the bacilli. The endospores have no reproductive significance, as only one spore is formed by each bacillus and a germinated spore yields a single bacillus. Spores form in soil and dead tissue and with no measurable metabolism may remain dormant for years. They are resistant to drying, heat, and many disinfectants. The genetic composition of B. anthracis differs little from the other Bacillus species, and studies have demonstrated remarkable similarity within B. anthracis strains. The resting stage of sporulation may have contributed to the extremely similar DNA of all strains of B. anthracis. The circular chromosomal DNA is composed of 5.2 million base pairs and codes for metabolic function, cell repair, and the sequential process of sporulation. Comparative genome sequencing has uncovered only four differences between the single-copy chromosomal DNA of two strains. In addition to the single-copy DNA, comprising the majority of the genome, a remaining portion consists of repetitive DNA sequences that are either dispersed or clustered into satellites. The satellite repeats occur in tandem. The number of tandem repeats varies among different strains; six chromosomal marker loci have been identified by multiple-locus variable number tandem repeat (VNTR) analysis. In addition to its chromosome, B. anthracis has two large plasmids that carry genes necessary for pathogenesis. The pXOl plasmid has 181,654 base pairs and contains the structural genes for the anthrax toxins cya (edema factor), lef (lethal factor), and pagA (protective antigen). The pXO2 plasmid consists of 96,231 base pairs and carries three genes required for synthesis of the capsule. These plasmids contain a much greater number of single nucleotide polymorphisms (SNPs) and VNTRs among strains than the chromosomal genome. There are a variety of reference strains, such as Pasteur (which lacks the XO1 plasmid), Sterne (which lacks the XO2 plasmid), and Ames (which has both plasmids and is fully virulent). Bioterrorism Anthrax spores can be easily packaged to act as aerosoled (airborne) agents of war, and the genome may be bioengineered to alter the virulence or effectiveness of current vaccines. Knowledge of the genetic composition of B. anthracis has facilitated the investigation of anthrax attacks. In 1993, the Aum Shinrikyo cult aerosoled a suspension of anthrax near Tokyo, Japan. Molecular studies of the genome from this strain revealed it to be devoid of the pXO2 plasmid (Sterne strain), explaining why only a bad odor rather than illness was the fortunate consequence. In 2001, analysis of material from letter-based attacks with anthrax in the United States demonstrated the source to be the Ames strain. Furthermore, as a result of the extensive laboratory studies associated with this attack, a sensitive and specific three-target (two-plasmid and one-chromosome) assay has been developed for rapid detection and identification of B. anthracis, including bioengineered strains, from both patients and the environment. H. Bradford Hawley See AlsoBacterial Genetics and Cell Structure; Bacterial Resistance and Super Bacteria; Biological Weapons; Plasmids; Smallpox. Further Reading Centers for Disease Control and Prevention. Bioterrorism-Related Anthrax: Emerging Infectious Diseases 8 (October, 2002): 1013-1183. Summarizes the investigation following the 2001 bioterrorism attacks in the United States. Dixon, Terry C., et al. "Anthrax." New England Journal of Medicine 341 (September 9, 1999): 815-826. Details the disease and its pathogenesis. Miller, Judith, Stephen Engelberg, and William Broad. Germs: Biological Weapons and America's Secret War. New York: Simon & Schuster, 2001. This book, written by three New York Times reporters, explores the ideas and actions of scientists and politicians involved in the past, present, and future of germ warfare. Forty-two pages of notes and a select bibliography. Read, Timothy D., et al. "Comparative Genome Sequencing for Discovery of Novel Polymorphisms in Bacillus anthracis." Science 296 (June 14, 2002): 2028-2033. Describes the complete sequencing of the anthrax genome. Web Sites of Interest Centers for Disease Control, Public Health Emergency Preparedness and Response. http://www.bt.cdc.gov. This comprehensive site offers information on how to recognize illness caused by anthrax exposure and more. Available in Spanish. Nature. http://www.nature.com. The online version of the premier science journal Nature includes links to research articles on the genetics of anthrax, including "Focus on Anthrax." |
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