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.
B. anthracis belongs to the B. cereus group of strains.
Structure of B. anthracis
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.
1 Historical background
2 Genome structure
2.1 pXO1 plasmid
2.2 pXO2 plasmid
4.1 Nearest neighbors
5 Clinical aspects
5.2 Manifestations in human disease
5.3 Prevention and treatment
6.1 Recent research
7 Host interactions
10 External links
CapD protein crystal structure of B. anthracis
Casimir Davaine (1812-1882) demonstrated the symptoms
of anthrax were invariably accompanied by the microbe B. anthracis.
Aloys Pollender (1799–1879) is credited for
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 anthrax (ἄνθραξ), meaning
"coal" and referring to the most common form of the disease, cutaneous
anthrax, in which large, black skin lesions are formed. Throughout the
Anthrax was an infection that involved several very
important medical developments. The first vaccine containing live
organisms was Louis Pasteur's veterinary anthrax vaccine.
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
Number of genes
Replicon coding (%)
Average gene length (nt)
G+C content (%)
Disrupted reading frame
Genes with assigned function
Conserved hypothetical genes
Genes of unknown function
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.
The 89 known strains of B. anthracis 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 a cow in Oxfordshire, UK, in 1935
Vollum M-36, virulent British research strain; passed through macaques
Vollum 1B, weaponized by the US and UK in the 1940s-60s
Vollum-14578, used in UK bio-weapons trials which severely
Gruinard Island in 1942
V770-NP1-R, the avirulent, nonencapsulated strain used in the BioThrax
Anthrax 836, highly virulent strain weaponized by the USSR; discovered
in Kirov in 1953
Ames strain, isolated from a cow in
Texas in 1981; famously used in
AMERITHRAX letter attacks (2001)
H9401, isolated from human patient in Korea; used in investigational
Whole genome sequencing has made reconstruction of the B. anthracis
phylogeny extremely accurate. A contributing factor to the
reconstruction is B. anthracis being monomorphic, meaning it has low
genetic diversity, including the absence of any measurable lateral DNA
transfer since its derivation as a species. The lack of diversity is
due to a short evolutionary history that has precluded mutational
saturation in single nucleotide polymorphisms.
A short evolutionary time does not necessarily mean a short
chronological time. When DNA is replicated, mistakes occur which
become genetic mutations. The buildup of these mutations over time
leads to the evolution of a species. During the B. anthracis
lifecycle, it spends a significant amount of time in the soil spore
reservoir stage, in which DNA replication does not occur. These
prolonged periods of dormancy have greatly reduced the evolutionary
rate of the organism.
B. anthracis belongs to the B. cereus group consisting of the strains:
B. cereus, B. anthracis, B. thuringiensis, B. weihenstephanensis, B.
mycoides, and B. pseudomycoides. The first three strains are
pathogenic or opportunistic to insects or mammals, while the last
three are not considered pathogenic. The strains of this group are
genetically and phenotypically heterogeneous overall, but some of the
strains are more closely related and phylogenetically intermixed at
the chromosome level. The B. cereus group generally exhibits complex
genomes and most carry varying numbers of plasmids.
B. cereus is a soil-dwelling bacterium which can colonize the gut of
invertebrates as a symbiont and is a frequent cause of food
poisoning It produces an emetic toxin, enterotoxins, and other
virulence factors. The enterotoxins and virulence factors are
encoded on the chromosome, while the emetic toxin is encoded on a
270-kb plasmid, pCER270.
B. thuringiensis is an insect pathogen and is characterized by
production of parasporal crystals of insecticidal toxins Cry and
Cyt. The genes encoding these proteins are commonly located on
plasmids which can be lost from the organism, making it
indistinguishable from B. cereus.
PlcR is a global transcriptional regulator which controls most of the
secreted virulence factors in B. cereus and B. thuringiensis. It is
chromosomally encoded and is ubiquitous throughout the cell. In B.
anthracis, however, the plcR gene contains a single base change at
position 640, a nonsense mutation, which creates a dysfunctional
protein. While 1% of the B. cereus group carries an inactivated plcR
gene, none of them carries the specific mutation found only in B.
The plcR gene is part of a two-gene operon with papR. The papR
gene encodes a small protein which is secreted from the cell and the
reimported as a processed heptapeptide forming a quorum-sensing
system. The lack of PlcR in B. anthracis is a principle
characteristic differentiating it from other members of the B. cereus
group. While B. cereus and B. thuringiensis depend on the plcR gene
for expression of their virulence factors, B. anthracis relies on the
pXO1 and pXO2 plasmids for its virulence.
Main article: Anthrax
B. anthracis possesses an antiphagocytic capsule essential for full
virulence. The organism also produces three plasmid-coded exotoxins:
edema factor, a calmodulin-dependent adenylate cyclase, causes
elevation of intracellular cAMP, and is responsible for the severe
edema usually seen in B. anthracis infections; lethal toxin is
responsible for tissue necrosis; protective antigen (so named because
of its use in producing protective anthrax vaccines) mediates cell
entry of edema factor and lethal toxin.
Manifestations in human disease
The symptoms in anthrax depend on the type of infection and can take
anywhere from 1 day to more than 2 months to appear. All types of
anthrax have the potential, if untreated, to spread throughout the
body and cause severe illness and even death.
Four 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).
Inhalation, a rare but highly fatal form, is characterized by flu like
symptoms, chest discomfort, diaphoresis, and body aches.
Gastrointestinal, a rare but also fatal (causes death to 25%) type,
results from ingestion of spores. Symptoms include: fever and chills,
swelling of neck, painful swallowing, hoarseness, nausea and vomiting
(especially bloody vomiting), diarrhea, flushing and red eyes, and
swelling of abdomen.
Injection, symptoms are similar to those of cutaneous anthrax, but
injection anthrax can spread throughout the body faster and can be
harder to recognize and treat compared to cutaneous anthrax.
Prevention and treatment
A number of anthrax vaccines have been developed for preventive use in
livestock and humans.
Anthrax vaccine adsorbed (AVA) may protect
against cutaneous and inhalation anthrax. However, this vaccine is
only used for at-risk adults before exposure to anthrax and has not
been approved for use after exposure. Infections with B. anthracis
can be treated with β-lactam antibiotics such as penicillin, and
others which are active against
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 B. 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. 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 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 Republic of Korea.
Since the genome of B. anthracis was sequenced, alternative ways to
battle this disease are being endeavored.
Bacteria have developed
several strategies to evade recognition by the immune system. The
predominant mechanism for avoiding detection, employed by all bacteria
is molecular camouflage. Slight modifications in the outer layer that
render the bacteria practically invisible to lysozymes. Three of
these modifications have been identified and characterized. These
include 1) N-glycosylation of N-acetyl-muramic acid, 2) O-acetylation
of N-acetylmuramic acid and 3) N-deacetylation of
N-acetyl-glucosamine. Research during the last few years has focused
on inhibiting such modifications. As a result the enzymatic
mechanism of polysaccharide de-acetylases is being investigated, that
catalyze the removal of an acetyl group from N-acetyl-glucosamine and
N-acetyl-muramic acid, components of the peptidoglycan layer.
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.
The presence of B. anthracis can be determined through samples taken
on non-porous surfaces.
How to sample with cellulose sponge on non-porous surfaces
How to sample with macrofoam swab on non-porous surfaces
^ a b Spencer, RC (March 2003). "
Bacillus anthracis". Journal of
clinical pathology. 56 (3): 182–7. doi:10.1136/jcp.56.3.182.
PMC 1769905 . PMID 12610093.
^ Holt, J. G., N. R. Krieg, P. H. A. Sneath, J. T. Staley, and S. T.
Williams. 1994. Group 17: gram-positive cocci, p. 527–558. In W. R.
Hensyl (ed.), Bergey's manual of determinative bacteriology, 9th ed.
Williams and Wilkins, Baltimore, Md.
^ Bergey's Manual of Systematic Bacteriology, vol. 2, p. 1105, 1986,
Sneath, P.H.A.; Mair, N.S.; Sharpe, M.E.; Holt, J.G. (eds.); Williams
& Wilkins, Baltimore, Maryland, USA
^ Zilinskas, Raymond A. (1999), "Iraq's Biological Warfare Program:
The Past as Future?", Chapter 8 in: Lederberg, Joshua (editor),
Biological Weapons: Limiting the Threat (1999), The MIT Press, pp
^ Théodoridès, J (April 1966). "
Casimir Davaine (1812-1882): a
precursor of Pasteur". Medical History. 10 (2): 155–65.
doi:10.1017/S0025727300010942. PMC 1033586 .
^ Koch, R. (1876) "Untersuchungen über Bakterien: V. Die Ätiologie
der Milzbrand-Krankheit, begründet auf die Entwicklungsgeschichte des
Bacillus anthracis" (Investigations into bacteria: V. The etiology of
anthrax, based on the ontogenesis of
Bacillus anthracis), Cohns
Beitrage zur Biologie der Pflanzen, vol. 2, no. 2, pages 277–310.
^ Sternbach G. "The History of Anthrax." Ncbi (2003): n. pag. Web.
^ a b Read, TD; Peterson, SN; Tourasse, N; Baillie, LW; Paulsen, IT;
Nelson, KE; Tettelin, H; Fouts, DE; Eisen, JA; Gill, SR; Holtzapple,
EK; Okstad, OA; Helgason, E; Rilstone, J; Wu, M; Kolonay, JF; Beanan,
MJ; Dodson, RJ; Brinkac, LM; Gwinn, M; DeBoy, RT; Madpu, R; Daugherty,
SC; Durkin, AS; Haft, DH; Nelson, WC; Peterson, JD; Pop, M; Khouri,
HM; Radune, D; Benton, JL; Mahamoud, Y; Jiang, L; Hance, IR; Weidman,
JF; Berry, KJ; Plaut, RD; Wolf, AM; Watkins, KL; Nierman, WC; Hazen,
A; Cline, R; Redmond, C; Thwaite, JE; White, O; Salzberg, SL;
Thomason, B; Friedlander, AM; Koehler, TM; Hanna, PC; Kolstø, AB;
Fraser, CM (May 1, 2003). "The genome sequence of
Ames and comparison to closely related bacteria". Nature. 423 (6935):
81–6. doi:10.1038/nature01586. PMID 12721629.
^ a b c d e f g Kolstø, Anne-Brit; Tourasse, Nicolas J.; Økstad, Ole
Andreas (1 October 2009). "What Sets Apart from Other Species?".
Annual Review of Microbiology. 63 (1): 451–476.
^ a b c d Chun, J.-H.; Hong, K.-J.; Cha, S. H.; Cho, M.-H.; Lee, K.
J.; Jeong, D. H.; Yoo, C.-K.; Rhie, G.-e. (18 July 2012). "Complete
Genome Sequence of
Bacillus anthracis H9401, an Isolate from a Korean
Patient with Anthrax". Journal of Bacteriology. 194 (15): 4116–4117.
doi:10.1128/JB.00159-12. PMC 3416559 .
^ a b Keim, Paul; Gruendike, Jeffrey M.; Klevytska, Alexandra M.;
Schupp, James M.; Challacombe, Jean; Okinaka, Richard (1 December
2009). "The genome and variation of
Bacillus anthracis". Molecular
Aspects of Medicine. 30 (6): 397–405. doi:10.1016/j.mam.2009.08.005.
PMC 3034159 . PMID 19729033.
^ Jensen, G. B.; Hansen, B. M.; Eilenberg, J.; Mahillon, J. (18 July
2003). "The hidden lifestyles of
Bacillus cereus and relatives".
Environmental Microbiology. 5 (8): 631–640.
doi:10.1046/j.1462-2920.2003.00461.x. PMID 12871230.
^ Drobniewski, FA (October 1993). "
Bacillus cereus and related
species". Clinical Microbiology Reviews. 6 (4): 324–38.
PMC 358292 . PMID 8269390.
^ Stenfors Arnesen, Lotte P.; Fagerlund, Annette; Granum, Per Einar (1
July 2008). "From soil to gut: and its food poisoning toxins". FEMS
Microbiology Reviews. 32 (4): 579–606.
doi:10.1111/j.1574-6976.2008.00112.x. PMID 18422617.
^ Schnepf, E; Crickmore, N; Van Rie, J; Lereclus, D; Baum, J;
Feitelson, J; Zeigler, DR; Dean, DH (September 1998). "Bacillus
thuringiensis and its pesticidal crystal proteins". Microbiology and
molecular biology reviews : MMBR. 62 (3): 775–806.
PMC 98934 . PMID 9729609.
^ Agaisse, H; Gominet, M; Okstad, OA; Kolstø, AB; Lereclus, D (June
1999). "PlcR is a pleiotropic regulator of extracellular virulence
factor gene expression in
Bacillus thuringiensis". Molecular
Microbiology. 32 (5): 1043–53. doi:10.1046/j.1365-2958.1999.01419.x.
^ Slamti, L; Perchat, S; Gominet, M; Vilas-Bôas, G; Fouet, A; Mock,
M; Sanchis, V; Chaufaux, J; Gohar, M; Lereclus, D (June 2004).
"Distinct mutations in PlcR explain why some strains of the Bacillus
cereus group are nonhemolytic". Journal of Bacteriology. 186 (11):
3531–8. doi:10.1128/JB.186.11.3531-3538.2004. PMC 415780 .
^ Okstad, OA; Gominet, M; Purnelle, B; Rose, M; Lereclus, D; Kolstø,
AB (November 1999). "Sequence analysis of three
Bacillus cereus loci
carrying PIcR-regulated genes encoding degradative enzymes and
enterotoxin". Microbiology. 145 (11): 3129–38.
doi:10.1099/00221287-145-11-3129. PMID 10589720.
^ a b Slamti, L; Lereclus, D (Sep 2, 2002). "A cell-cell signaling
peptide activates the PlcR virulence regulon in bacteria of the
Bacillus cereus group". The EMBO Journal. 21 (17): 4550–9.
doi:10.1093/emboj/cdf450. PMC 126190 .
^ Bouillaut, L; Perchat, S; Arold, S; Zorrilla, S; Slamti, L; Henry,
C; Gohar, M; Declerck, N; Lereclus, D (June 2008). "Molecular basis
for group-specific activation of the virulence regulator PlcR by PapR
heptapeptides". Nucleic Acids Research. 36 (11): 3791–801.
doi:10.1093/nar/gkn149. PMC 2441798 . PMID 18492723.
^ a b c d "Symptoms". Centers for Disease Control and Prevention.
Retrieved 16 November 2015.
^ Barnes JM (1947). "
Penicillin and B. anthracis". J Path Bacteriol.
194: 113–125. doi:10.1002/path.1700590113.
Anthrax and tea". Society for Applied Microbiology. 2011-12-21.
Archived from the original on February 13, 2009. Retrieved
^ Callewaert L, Michiels CW. Lysozymes in the animal kingdom. J Biosci
35(1): (2010); 127-60.
^ Balomenou, Stavroula, Sofia Arnaouteli, Dimitris Koutsioulis,
Vassiliki E. Fadouloglou, and Vassilis Bouriotis. "Polysaccharide
Deacetylases: New Antibacterial Drug Targets."Frontiers in
Anti-Infective Drug Discovery 4 (2015): 68-130.
^ Maresso AW, Garufi G, Schneewind O (2008). "
Secretes Proteins That Mediate
Heme Acquisition from Hemoglobin". PLOS
Pathogens. 4 (8): e1000132. doi:10.1371/journal.ppat.1000132.
Wikimedia Commons has media related to
Bacillus anthracis genomes and related information at PATRIC, a
Bioinformatics Resource Center funded by NIAID
Hazards in Animal Research Database -
Firmicutes (low-G+C) Infectious diseases
Bacterial diseases: G+
primarily A00–A79, 001–041, 080–109
Viridans streptococci: S. mitis
bacitracin susceptible: S. pyogenes
Group A streptococcal infection
bacitracin resistant, CAMP test+: S. agalactiae
Group B streptococcal infection
Streptococcus iniae infection
Urinary tract infection
Staphylococcal scalded skin syndrome
Toxic shock syndrome
Clostridial necrotizing enteritis
Peptostreptococcus (non-spore forming)