DEFINITION
Bacillus anthracis is a large Gram-positive, aerobic, spore bearing, rod-shaped bacterium, 1–1.5 × 3–10 μm in size.
It is the only bacterium known to synthesize a protein capsule (D-glutamate) and it is the only obligate pathogen within the genus bacillus.
Anthrax is an acute infection caused by the spore-forming bacteria BACILLUS ANTHRACIS. It commonly affects hoofed animals such as sheep and goats. Infection in humans often involves the skin (cutaneous anthrax), the lungs (inhalation anthrax), or the gastrointestinal tract.
The spore has a capacity to survive in the environment for decades.
Bacillus anthracis is the pathogen of the Anthrax disease. Anthrax is not contagious and can be treated with antibiotics.
Bacillus anthracis secretes edema factor (EF) to disrupt intracellular signaling pathways.
Upon translocation into host cells and association with a calcium sensor, calmodulin (CaM), EF becomes a highly active adenylyl cyclase (AC) that raises the intracellular concentration of cyclic AMP. This strategy is also used by Bordetella pertussis, a bacterium that causes whooping cough.
The major distinguishing feature of B. anthracis is the presence of two large virulence plasmids, pXO1 and pXO2, that harbor the tripartite toxin complex and the genes responsible for the synthesis of a poly-γ-d-glutamic acid capsule, respectively.
Plasmid pXO2 (60 MDa) carries genes required for the synthesis of an antiphagocytic poly-d-glutamic acid capsule.
The 110-MDa plasmid pXO1 is required for synthesis of the anthrax toxin proteins, edema factor, lethal factor, and protective antigen.
These proteins act in binary combinations to produce the two anthrax toxins: edema toxin (a protective antigen and edema factor) and lethal toxin (a protective antigen and lethal factor).
Noninvasive imaging technologies reveal edema toxin as a key virulence factor in anthrax.Am J Pathol. 2011 Jun;178(6):2523-35.
Model for the catalytic activation of EF by CaM
The Adenylyl Cyclase Activity of Anthrax Edema Factor
Role of luxS in Bacillus anthracis growth and virulence factor expression [Virulence 1:2, 72-83; March/April 2010; © 2010 Landes Bioscience]
Quorum-sensing (QS), the regulation of bacterial gene expression in response to changes in cell density, involves pathways that synthesize signaling molecules (auto-inducers). The luxS/AI-2-mediated QS system has been identified in both Grampositive and Gram-negative bacteria. Bacillus anthracis, the etiological agent of anthrax, possesses genes involved in luxS/AI-2-mediated QS, and deletion of luxS in B.anthracis Sterne strain 34F2 results in inhibition of AI-2 synthesis and a growth defect.
Anthrax Animation
Sequence and Organization of pXO1, the Large Bacillus anthracis Plasmid Harboring the Anthrax Toxin Genes [J Bacteriol. 1999 October; 181(20): 6509–6515.]
Bacillus anthracis virulence plasmid PX01, complete sequence
EPIDEMIOLOGY
Anthrax is a worldwide zoonosis to which most animals, especially grazing herbivores, are susceptible. In natural conditions, human infections (predominantly cutaneous) usually result from contact with infected animals or contaminated animal products, such as hides or wool. Cases of inhalation anthrax (woolsorters’ disease) have occurred in enclosed factory spaces where large scale processing of hides and wool took place.
The ability of the anthrax spore to produce disease by the respiratory route is not high. Inhaled spores of > 5 μm pose no threat because they are cleared from the lung by the mucociliary escalator system. Lincoln and colleagues quote a spore load figure for sheep, generally regarded as very susceptible to anthrax, of 200 000.
Humans are generally regarded as being moderately resistant to anthrax. Using air sampling techniques, Dahlgren and co-workers estimated that in one woollen mill, workers were inhaling between 600 and 1300 spores during an eight hour shift with no ill effects.
Zimbabwe saw the largest human epidemic to date, where more than 10 000 human cases, nearly all of them cutaneous, were reported between 1979 and 1985.
Three main lessons were learnt from this outbreak, namely: (1) the importance of vaccinating livestock on a regular basis in areas of endemicity; (2) direct contact with infected livestock has a major role in human acquisition; and (3) there seems to be little risk of cross infection from infected patients to health care workers or other patients.
SYMPTOMS
Cutaneous anthrax. After infection via an abrasion, cut, or possible insect bite, a small pimple or papule will develop within two to three days, although there are reports of incubation periods as short as 12 hours or as long as 19 days.
In untreated anthrax, about 20% of patients may develop septicaemia and die, but with the use of appropriate antibiotics the mortality rate is < 1%.
Gastrointestinal anthrax. This form of disease results from the ingestion of undercooked meat from animals with B anthracis.
Inhalation anthrax. The illness begins insidiously with “flu-like” symptoms of mild fever, fatigue, malaise, myalgia, and non-productive cough, usually two to five days after the initial exposure. This mild initial prodromal phase, which usually lasts about 48 hours, suddenly ends with the development of an acute illness characterised by acute dyspnoea, stridor, fever, and cyanosis. On examination at this time, the findings include fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion. Terminally, the pulse becomes extremely rapid and faint, dyspnoea and cyanosis worsen, the patient becomes extremely disorientated, and this is quickly followed by coma and death.
DIAGNOSIS
Gram’s stained smear of the skin lesion (vesicle or eschar), blood, or cerebrospinal fluid, demonstrating encapsulated, large Gram positive bacilli (box car shaped) in short chains.
h3. PATHOGENESIS.
Serological testing is only of use retrospectively and requires acute and convalescent sera for comparison.
Matrix metalloproteinase-activated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature. J Biol Chem. 2008 Jan 4;283(1):529-40. Epub 2007 Nov 1.
TISSUE SPECIFIC RISK FACTORS
Fatal Pneumonia among Metalworkers Due to Inhalation Exposure to Bacillus cereus Containing Bacillus anthracis Toxin Genes
COMPLICATIONS
Anthrax meningitis can occur as an end stage process of any of the forms of anthrax.
THERAPY
Penicillin has long been considered the drug of choice and only rarely has penicillin resistance been found in naturally occurring strains. In vitro B anthracis is susceptible to penicillins, fluoroquinolones, tetracycline, chloramphenicol, aminoglycosides, macrolides, imipenem/meropenem, rifampicin, and vancomycin. The organism is resistant to cephalosporins, trimethoprim, and sulfomanides.
Treatment protocols for inhalation anthrax, J Clin Pathol. 2003 March; 56(3): 182–187.
Recommended prophylaxis after exposure toBacillus, J Clin Pathol. 2003 March; 56(3): 182–187. anthracis
