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 1-1.2µm and a length of 3-5µm. 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 (D-glutamate). Like Bordetella pertussis, it forms a calmodulin-dependent adenylate cyclase exotoxin known as (edema factor), along with 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 spores in particular are highly resilient, surviving extremes of temperature, low-nutrient environments, and harsh chemical treatment over decades or centuries.
The spore 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 is sometimes called an endospore, because 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 that they have a thin outer spore coat, a thick spore cortex, and an inner spore membrane surrounding the spore contents. The spores resist heat, drying, and many disinfectants (including 95% ethanol).
French physician Casimir Davaine (1812-1882) demonstrated the symptoms of anthrax were invariably accompanied by the microbe B. anthracis. German physician Aloys Pollender (1799–1879) is also credited for this discovery. B. anthracis was the first bacterium conclusively demonstrated to cause disease, by Robert Koch in 1876. The species name anthracis is from the Greek anthrakis (ἄνθραξ), meaning "coal" and referring to the most common form of the disease, cutaneous anthrax, in which large, black skin lesions are formed.
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.
|Number of genes||5,508||217||113|
|Replicon coding (%)||84.3||77.1||76.2|
|Average gene length (nt)||800||645||639|
|G+C content (%)||35.4||32.5||33.0|
|Disrupted reading frame||37||5||7|
|Genes with assigned function||2,762||65||38|
|Conserved hypothetical genes||1,212||22||19|
|Genes of unknown function||657||8||5|
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). Interestingly, AcpA and AcpB expression are under the control of AtxA from pXO1.
There are 89 known strains of B. anthracis. Notable examples include:
- Sterne strain (34F2; aka the "Weybridge strain"), used by Max Sterne in his 1930s vaccines
- Vollum strain, formerly weaponized by the US, UK and Iraq; isolated from cow in Oxfordshire, UK, in 1935
- Ames strain, isolated from cow in Texas, USA, in 1981; famously used in AMERITHRAX letter attacks (2001)
- Ames Ancestor
- Ames Florida
- H9401, isolated from human patient in Korea; used in investigational anthrax vaccines
|This section requires expansion. (October 2012)|
Manifestations in human disease
Three forms of human anthrax disease are recognized based on their portal of entry.
- Cutaneous, the most common form (95%), causes a localized, inflammatory, black, necrotic lesion (eschar).
- Pulmonary, the highly fatal form, is characterized by sudden, massive chest edema followed by cardiovascular shock.
- Gastrointestinal, a rare but also fatal (causes death to 25%) type, results from ingestion of spores.
Prevention and treatment
A number of anthrax vaccines have been developed for preventive use in livestock and humans. Infections with B. anthracis can be treated with β-lactam antibiotics such as penicillin, and others which are active against Gram-positive bacteria. Penicillin-resistant B. anthracis can be treated with fluoroquinolones such as ciprofloxacin or tetracycline antibiotics such as doxycycline.
Components of tea, such as polyphenols, have the ability to inhibit the activity both of Bacillus anthracis and its toxin considerably; spores, however, are not affected. The addition of milk to the tea completely inhibits its antibacterial activity against anthrax. Activity against the B. athracis in the laboratory does not prove that drinking tea affects the course of an infection, since it is unknown how these polyphenols are absorbed and distributed within the body .
Advances in genotyping methods have led to improved genetic analysis for variation and relatedness. These methods include multiple-locus variable-number tandem repeat analysis (MLVA) and typing systems using canonical single-nucleotide polymorphisms (SNPs). The Ames ancestor chromosome was sequenced in 2003 and contributes to the identification of genes involved in the virulence of B. anthracis. Recently, B. anthracis isolate H9401 was isolated from a Korean patient suffering from gastrointestinal anthrax. The goal of the Republic of Korea is to use this strain as a challenge strain to develop a recombinant vaccine against anthrax.
The H9401 strain isolated in the Republic of Korea was sequenced using 454 GS-FLX technology and analyzed using several bioinformatics tools to align, annotate, and compare H9401 to other B. anthracis strains. The sequencing coverage level suggests a molecular ratio of pXO1:pXO2:chromosome as 3:2:1 which is identical to the Ames Florida and the Ames Ancestor strains. H9401 has 99.679% sequence homology with Ames Ancestor with an amino acid sequence homology of 99.870%. H9401 has a circular chromosome (5,218,947 bp with 5,480 predicted ORFs), the pXO1 plasmid (181,700 bp with 202 predicted ORFs), and the pXO2 plasmid (94,824 bp with 110 predicted ORFs). As compared to the Ames Ancestor chromosome above, the H9401 chromosome is about 8.5 kb smaller. Due to the high pathogenecity and sequence similarity to the Ames Ancestor, H9401 will be used as a reference for testing the efficacy of candidate anthrax vaccines by the Repbulic of Korea.
As with most other pathogenic bacteria, B. anthracis must acquire iron to grow and proliferate in its host environment. The most readily available iron sources for pathogenic bacteria are the heme groups used by the host in the transport of oxygen. To scavenge heme from host hemoglobin and myoglobin, B. anthracis uses two secretory siderophore proteins, IsdX1 and IsdX2. These proteins can separate heme from hemoglobin, allowing surface proteins of B. anthracis to transport it into the cell.
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