The pathogenesis of Bacillus anthracis

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By [Tony Amolo]

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Anthrax is a highly contagious disease caused by the bacteria named Bacillus anthracis from the family Bacillaceae. It is the only obligate bacillus pathogen in vertebrates as other Bacillus species are harmless saprophytes. Based on phenotype, it can be classed with Bacillus cereus, Bacillus thuringiensis and Bacillus mycoides as it is difficult to differentiate this group based on their 16S rRNA sequences (10). The genus includes thermophilic, psychrophilic, acidophilic, alkaliphilic, halotolerant, and halophilic, which are capable of growing at temperatures, pH values, and salt concentrations at which few organisms could survive.(4) Named by Hippocrates for the black skin lesions it causes in its cutaneous form, anthrax( Greek: “coal) was well known in the ancient past and is featured in two of the ten plagues of the Old Testament.(1) It generally affects warm blooded animals including humans. Aloys Pollender, who is credited with discovering the disease called the organism “chyllus corpuscles” in the blood spleen, and carbuncle fluid of cows, which had died of the disease (2). Anthrax was extensively studied in the 1870s by Robert Koch and Louis Pasteur. Koch used suspended drop culture methods to trace the complete life cycle of the bacteria and found that the spores formed could remain viable for long period of adverse environments (3). It became a matter of public interest after the bioterrorist attacks in the USA during the autumn of 2001 where five letters containing small quantities of anthrax spores contaminated more than 30,000 people, killed five people and infected 17. (13)

Cell Structure and Metabolism

Bacillus anthracis is an endospore forming aerobic or facultative anaerobic, rod shaped, immobile and capsulated bacteria. It is a gram positive bacteria but in some cultures may turn gram negative with age (4). Bacillus anthracis is 1-1.5micrometer wide by 5-6 micrometer in length. They look like bamboo canes in tissue (13). Many species of its genus exhibits a wide range of abilities that allow them to live in different natural environment. (4) They have the ability to form only one endospore per cell. These spores are usually formed when vegetative cells are deprived of certain nutrient. Bacillus anthracis requires oxygen to sporulate and its spores are resistant to cold, heat, radiation, desiccation and disinfectants.(8) Spores are oval and sporulation occurs within 48hours. Spore formation begins with asymmetric septation then the mother cell engulfs the forespore and protects it with three layers called the coat, cortex and exosporium. The exosporium is a loose-fitting, balloon-like structure enclosing a spore that has been studied to understand the use of anthrax as a weapon. Concerns about the use of Bacillus anthracis spores as a biological weapon have resulted in efforts to understand the interactions between Bacillus anthracis and the cells of the mammalian immune system, and to develop better detectors for these spores. (8) Bacillus anthracis has been successful as a bioweapon because of its tough resistant endospore and its ability to cause lethal inhalational anthrax.

Habitat and Ecology

Bacillus anthracis is mostly found in the agricultural regions of Central and South America, sub-saharan Africa, central and southwestern Asia, southern and eastern Europe, and the Caribbean. It is a soil borne bacteria. It lives best in black steppe soils especially chernozem and kastanozem, rich in organic matter and calcium at pH levels between (7-9). Endemic anthrax areas have been associated with warmer temperatures, higher soil moisture content and topography (15). Most research suggests that germination and multiplication occurs in the host while spore survival occurs in the soil.

Pathogenesis and Virulence factors

Bacillus anthracis depends on two toxic factors from two plasmids:
the pX01, 182kb,which encodes the genes for the edema factor (EF), the lethal factor (LF) and the protective antigen (PA), and the
pX02, 96kb, which encodes the genes for the biosynthesis of the capsule. Bacillus anthracis expresses it pathogenic action mainly through the capsule and the production of a toxic complex consisting of three proteins(EF, LF and PA). (13) The lethal toxin(LT, the combination of PA and LF) and edema toxin (ET, the combination of PA and EF) are sufficient to produce many of the symptoms of anthrax infection.(7) Of the three factors, the PA plays a fundamental role in the toxic action of Bacillus anthracis. Protective antigen (735 amino acids) plays an important role in anthrax intoxication by mediating the attachment and entry of the lethal factor and Edema factor into the cytosol. It contains regions involved in binding to the cell receptor, binding LF and EF, membrane insertion, and translocation of the anthrax toxin. Protective antigen is a major immunogen present in anthrax vaccines(11). The edema factor(89kDa) is a calcium and calmodulin-dependent adenylate cyclase that causes a dramatic increase in cytoplasmic cAMP leading to an imbalance of water homeostasis. The edema toxin may increase host susceptibility to infection by disrupting the cytokine response of monocytes and by suppressing neutrophil functions (11). The lethal factor is a Zn2+ dependent metalloprotease that cleaves major pathways to surface receptors for the transcription of certain genes within the nucleus(12) while the capsule enhances the virulence by inhibiting the phagocytosis of bacillus anthracis. Anthrax toxins provided a mechanism of trans-membrane translocation of proteins, the discovery of plasmids pXO1 and pXO2 which allowed the study of virulence factors at a genetic level(5).


[1] Hodgkin, J. and Partridge, F.A. "Caenorhabditis elegans meets microsporidia: the nematode killers from Paris." 2008. PLoS Biology 6:2634-2637.

Authored for BIOL 238 Microbiology, taught by Joan Slonczewski, 2015, Kenyon College.

Vaccines and Cure/Current Research

Include some current research, with at least one figure showing data.