Bacillus anthracis

Bacillus anthracis is the etiologic agent of anthrax—a common disease of livestock and, occasionally, of humans—and the only obligate pathogen within the genus Bacillus. B. anthracis is a Gram-positive, endospore-forming, rod-shaped bacterium, with a width of 1.0–1.2 µm and a length of 3–5 µm. It can be grown in an ordinary nutrient medium under aerobic or anaerobic conditions. It is one of few bacteria known to synthesize a protein capsule (poly-D-gamma-glutamic acid). Like Bordetella pertussis, it forms a calmodulin-dependent adenylate cyclase exotoxin known as anthrax edema factor, along with anthrax lethal factor. It bears close genotypical and phenotypical resemblance to Bacillus cereus and Bacillus thuringiensis. All three species share cellular dimensions and morphology. All form oval spores located centrally in an unswollen sporangium. B. anthracis endospores, in particular, are highly resilient, surviving extremes of temperature, low-nutrient environments, and harsh chemical treatment over decades or centuries. The endospore is a dehydrated cell with thick walls and additional layers that form inside the cell membrane. It can remain inactive for many years, but if it comes into a favorable environment, it begins to grow again. It initially develops inside the rod-shaped form. Features such as the location within the rod, the size and shape of the endospore, and whether or not it causes the wall of the rod to bulge out are characteristic of particular species of Bacillus. Depending upon the species, the endospores are round, oval, or occasionally cylindrical. They are highly refractile and contain dipicolinic acid. Electron micrograph sections show they have a thin outer endospore coat, a thick spore cortex, and an inner spore membrane surrounding the endospore contents. The endospores resist heat, drying, and many disinfectants (including 95% ethanol). Because of these attributes, B. anthracis endospores are extraordinarily well-suited to use (in powdered and aerosol form) as biological weapons. Such weaponization has been accomplished in the past by at least five state bioweapons programs—those of the United Kingdom, Japan, the United States, Russia, and Iraq—and has been attempted by several others. B. anthracis are rod-shaped bacteria, approximately 3 to 5 micrometers long and 1 to 1.2 micrometers wide. When grown in culture, they tend to form long chains of bacteria. On agar plates, they form large colonies several millimeters across that are generally white or cream colored. Most B. anthracis strains produce a capsule that gives colonies a slimy mucus-like appearance. B. anthracis has a single chromosome which is a circular, 5,227,293-bp DNA molecule. It also has two circular, extrachromosomal, double-stranded DNA plasmids, pXO1 and pXO2. Both the pXO1 and pXO2 plasmids are required for full virulence and represent two distinct plasmid families. The pXO1 plasmid (182 kb) contains the genes that encode for the anthrax toxin components: pag (protective antigen, PA), lef (lethal factor, LF), and cya (edema factor, EF). These factors are contained within a 44.8-kb pathogenicity island (PAI). The lethal toxin is a combination of PA with LF and the edema toxin is a combination of PA with EF. The PAI also contains genes which encode a transcriptional activator AtxA and the repressor PagR, both of which regulate the expression of the anthrax toxin genes. pXO2 encodes a five-gene operon (capBCADE) which synthesizes a poly-γ-D-glutamic acid (polyglutamate) capsule. This capsule allows B. anthracis to evade the host immune system by protecting itself from phagocytosis. Expression of the capsule operon is activated by the transcriptional regulators AcpA and AcpB, located in the pXO2 pathogenicity island (35 kb). AcpA and AcpB expression are under the control of AtxA from pXO1.