What Sets Bacillus Anthracis Apart From Other Bacillus Species?

ANRV387-MI63-22 ARI 5 August 2009 10:48
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REVIEWS Further What Sets Bacillus anthracis
Apart from Other Bacillus
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Annu. Rev. Microbiol. 2009.63:451-476. Downloaded from www.annualreviews.org
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Anne-Brit Kolstø, Nicolas J. Tourasse,
and Ole Andreas Økstad
Laboratory for Microbial Dynamics and Department of Pharmaceutical Biosciences, School
of Pharmacy, University of Oslo, 0316 Oslo, Norway; email: a.b.kolsto@farmasi.uio.no
Annu. Rev. Microbiol. 2009. 63:451–76 Key Words

First published online as a Review in Advance on Bacillus cereus group, classification, phylogeny, plasmids, clonal lineage
June 10, 2009
The Annual Review of Microbiology is online at Abstract

micro.annualreviews.org
Bacillus anthracis is the cause of anthrax, and two large plasmids are es-
This article’s doi: sential for toxicity: pXO1, which contains the toxin genes, and pXO2,
10.1146/annurev.micro.091208.073255
which encodes a capsule. B. anthracis forms a highly monomorphic lin-
Copyright c 2009 by Annual Reviews. eage within the B. cereus group, but strains of Bacillus thuringiensis and
All rights reserved
B. cereus exist that are genetically closely related to the B. anthracis clus-
0066-4227/09/1013-0451$20.00 ter. During the past five years B. cereus strains that contain the pXO1 vir-
ulence plasmid were discovered, and strains with both pXO1 and pXO2
have been isolated from great apes in Africa. Therefore, the presence of
pXO1 and pXO2 no longer principally separates B. anthracis from other
Bacilli. The B. anthracis lineage carries a specific mutation in the global
regulator PlcR, which controls the transcription of secreted virulence
factors in B. cereus and B. thuringiensis. Coevolution of the B. anthracis
chromosome with its plasmids may be the basis for the successful de-
velopment and uniqueness of the B. anthracis lineage.
451
Contents
INTRODUCTION . . . . . . . . . . . . . . . . . . 452 B. anthracis . . . . . . . . . . . . . . . . . . . . . . . . 460
BACILLUS SPECIES . . . . . . . . . . . . . . . . . 453 Other B. cereus Group Genomes . . . . 461
THE BACILLUS CEREUS GROUP . . 453 pXO1 AND pXO2 PLASMID
B. anthracis . . . . . . . . . . . . . . . . . . . . . . . . 453 FAMILIES . . . . . . . . . . . . . . . . . . . . . . . . 461
B. cereus . . . . . . . . . . . . . . . . . . . . . . . . . . . 453 pXO1 Family . . . . . . . . . . . . . . . . . . . . . . 465
B. thuringiensis . . . . . . . . . . . . . . . . . . . . . 457 pXO2 Family . . . . . . . . . . . . . . . . . . . . . . 465
PlcR: A NONFUNCTIONAL B. cereus Strains Carrying pXO1
GLOBAL REGULATOR IN and pXO2 . . . . . . . . . . . . . . . . . . . . . . 465
BACILLUS ANTHRACIS . . . . . . . . . . 457 Plasmid Distribution and
POPULATION STRUCTURE Chromosomal Relationships . . . . . 466
AND CLASSIFICATION OF THE DYNAMICS OF BACILLUS CEREUS

BACILLUS CEREUS GROUP . . . . . 459 GROUP GENOMES . . . . . . . . . . . . . 466

Population Structure as Analyzed by Plasmids and Phages . . . . . . . . . . . . . . . 466
Molecular Typing Methods . . . . . . 459 Other Mobile DNA and
B. anthracis and B. cereus RNA Elements . . . . . . . . . . . . . . . . . 467
Clonal Clusters . . . . . . . . . . . . . . . . . 460 CONCLUSIONS AND FUTURE
Differentiating B. anthracis Isolates RESEARCH . . . . . . . . . . . . . . . . . . . . . . 468
and the Identification of B. The Species: What is in a Name? . . . 468
anthracis Near-Neighbors . . . . . . . 460 pXO1 and pXO2: Key Players in the
WHOLE-GENOME SEQUENCING Evolution Toward a
OF BACILLUS CEREUS GROUP Monomorphic Lineage? . . . . . . . . . 469
STRAINS . . . . . . . . . . . . . . . . . . . . . . . . . 460
INTRODUCTION of the disease, with high lethality. B. anthracis

virulence mechanisms allow the spread of the
Bacillus anthracis is the etiological agent of an- bacteria to lymph nodes and later dissemination
thrax, a historical disease that has been de- to the bloodstream and internal organs (59).
scribed in ancient literature dating back more Although the host range of B. anthracis is
than 2000 years, including the biblical Book the vertebrates, including all mammals, anthrax
of Exodus, in which it is described as the fifth disease mainly affects wild and domesticated
plague of Egypt. The causal relationship was herbivores. B. anthracis has been considered a
conclusively shown by Robert Koch in 1876 potential biowarfare agent during the age of
(45), at the same time providing the first evi- the Cold War, and in later years as a bioter-
dence that a specific microorganism could cause ror agent. Increased awareness of B. anthracis
a specific disease in an animal. The bacterium as the cause of anthrax disease arose in 2001,
was also used in Pasteur’s public demonstration following the September/October anthrax ter-
of vaccination in 1881 at Pouilly-le-Fort (66). ror attacks in the United States, where spores
B. anthracis is found worldwide in the soil, al- were spread in letters transported by the U.S.
though sporadically, and may infect most mam- Postal Service (40), causing the death of 5
mals including humans, causing human disease people and infecting 17 others. These events
either through local infection of skin lesions have triggered a dramatic increase in scientific
(cutaneous anthrax), through the gastrointesti- research on B. anthracis, with the average num-
nal route, or by inhalation. Inhalational and gas- ber of publications per year raising from about
trointestinal anthrax are the most severe forms 20 to more than 100 since 2002.
452 Kolstø · Tourasse · Økstad

BACILLUS SPECIES phenotypic traits of the B. cereus group species

B. anthracis is a spore-forming, gram-positive are carried by plasmids, has led to intense
bacterium belonging to the genus Bacillus, debates regarding the species definitions
Prophage: a
within the family Bacillaceae. Bacilli are het- within the group (28, 70). Some B. cereus and bacteriophage that has
erogeneous, reflected in a highly variable GC B. thuringiensis strains are closely related to integrated into the
content (33–78%) and in their 16S rRNA B. anthracis phylogenetically (Figure1c). This genome of the host
review deals with the relationship between bacterium in a process
phylogeny (Figure 1a). B. subtilis is the most called lysogeny
thoroughly studied Bacillus species, is generally B. anthracis and its relatives in the B. cereus
group. Pathogenicity island
regarded as nonpathogenic, and has been used (PAI): a genomic
as a model gram-positive bacterium for many region, typically
years. Other species, such as B. anthracis and B. anthracis 10–200 kb in length,
B. cereus, may cause disease. A common feature carrying genes
B. anthracis is highly monomorphic, i.e., it
encoding one or more
for Bacilli is the production of endospores, shows little genetic variation (Figure 1c) (100),
virulence factors
dormant structures resistant to chemicals, heat, and primarily exists in the environment as a
UV light, and desiccation, when the cell experi- highly stable, dormant spore in the soil. Never-
ences starvation or other specific environmental theless, there is evidence that the organism can
stresses. grow and persist outside the host in the rhi-
zosphere of plants (77). The main features of
THE BACILLUS CEREUS GROUP B. anthracis are the two large plasmids, pXO1
(182 kb) and pXO2 (95 kb), both of which are
The B. cereus group (B. cereus sensu lato)
necessary for full virulence (59) and represent
is a subgroup of related Bacilli (Figure 1)
two distinct plasmid families. pXO1 contains
containing six species: B. weihenstephanensis,
the genes coding for the anthrax toxin compo-
B. mycoides, B. pseudomycoides, B. cereus, B.
nents, pag (protective antigen, PA), lef (lethal
thuringiensis, and B. anthracis. The last three
factor, LF), and cya (edema factor, EF), located
species are opportunistic or pathogenic to
within a 44.8-kb pathogenicity island (PAI) (61).
insects or mammals, whereas the first three
Together with PA, LF or EF forms the bipar-
are generally regarded as nonpathogenic.
tite lethal toxin or edema toxin, respectively
Altogether these Bacilli are found in diverse
(104). The PAI also encodes the transcriptional
habitats, including various types of soils, the
activator AtxA and the repressor PagR, which
gut of soil-dwelling invertebrates, the plant
regulate the expression of the toxins (12, 17,
rhizosphere, and in human-made settings such
46, 57, 95). pXO2 contains a five-gene operon
as food production factories (39). Although the
(capBCADE ) for the biosynthesis of a poly-
B. cereus group is phenotypically and genetically
γ-d-glutamic acid (polyglutamate) capsule, a
heterogeneous overall, strains of the same and,
structure that is important for the ability to
most strikingly, of different species may be
evade the host immune system, by protecting
closely related and phylogenetically intermixed
the vegetative cells from phagocytotic killing by
at the chromosomal level (Figure 1b). B. cereus
macrophages (9, 14). Capsule expression is ac-
group members generally exhibit complex
tivated by the transcriptional regulators AcpA
genomes, as most strains carry plasmids in
and AcpB, which again are under the control
various numbers (1−>12) and sizes (2–600 kb;
of AtxA from pXO1 (17, 68), and the capsule
frequently >80 kb), have unique chromosomal
operon and its regulators are part of a 35-kb
interspersed sequence repeats (63, 92), and/or
PAI on pXO2 (65, 98).
contain bacteriophages that may be integrated
into the chromosome as prophages (Figure 2)
or replicate as independent linear elements B. cereus
(47, 70, 86). The phylogenetic intermixing B. cereus is a common soil bacterium and can col-
of strains, and the fact that some of the main onize invertebrate guts as a symbiont (39). It is a
www.annualreviews.org • What Sets Bacillus anthracis Apart from Other Bacillus Species? 453
a Bacilli
0.02
Sporosarcina_psychrophilus
Sporosarcina_pasteurii
Bacillus_insolitus
Lysinibacillus_sphaericusG
Bacillus_sp._B-14905G
Marinibacillus_marinus
Bacillus_subtilisG
Bacillus_mojavensisg
Bacillus_amyloliquefaciensG
Bacillus_licheniformisG
Bacillus_pumilusG
Bacillus_coahuilensisG
Bacillus_sp._SG-1.G
Bacillus_anthracisG
Bacillus_cereusG
Bacillus_thuringiensisG
Bacillus_weihenstephanensisG B. cereus
Bacillus_mycoidesg group
g
Bacillus_pseudomycoides (continued
Bacillus_cereus_cytotoxisG on next
Bacillus_halmapalus page)
Bacillus_horikoshii
Bacillus_acidiceler
Bacillus_luciferensis
Bacillus_fastidiosus
Bacillus_carboniphilus
Bacillus_badius
Bacillus_lentusg
Bacillus_oleronius
Bacillus_megateriumg
Bacillus_simplex
Bacillus_flexus
Bacillus_psychrosaccharolyticus
Bacillus_niacini
Bacillus_infernus
Bacillus_firmus
Bacillus_benzoevorans
Bacillus_circulans
Oceanobacillus_iheyensisG
Bacillus_pseudoalcaliphilus
Bacillus_alcalophilusg
Bacillus_clausiiG
Bacillus_haloduransG
Bacillus_selenitireducensG
Bacillus_agaradhaerens
Bacillus_clarkii
Bacillus_coagulansG
Geobacillus_kaustophilusG
Geobacillus_stearothermophilusg
Geobacillus_thermodenitrificansG
Geobacillus_pallidus
Bacillus_thermoamylovorans
Bacillus_thermocloacae
Bacillus_horti
Paenibacillus_chitinolyticus
Bacillus_schlegelii
g
Bacillus_tusciae
Alicyclobacillus_acidocaldariusg
frequent cause of food poisoning and is also re- (cereulide, which is a small, heat-stable non-
sponsible for various opportunistic and nosoco- ribosomally synthesized dodecadepsipeptide)
mial infections (see Reference 13 for a review). or enterotoxins (87). Other virulence factors
B. cereus can cause two food-poisoning syn- include secreted phospholipases, hemolysins,
dromes, due to the production of emetic toxin proteases, and other degradative enzymes. The

b B. cereus group c B. anthracis neighbors

0.05 0.002
B.anthracis_AmesAncG B.anthracis_A1055G C
B.thuringiensis_BGSC_4AJ1 B.anthracis_CNEVAG
B.c_group_AH820G B.anthracis_KrugerBG
B
B.cereus_WG B.anthracis_Tsiankovskii-IG
B.cereus_03BB108G B.anthracis_VollumG
B.cereus_NVH0597-99G B.anthracis_FloridaG
B.thuringiensis_97-27G
B.anthracis_AustraliaG
B.c_group_CI A
B.anthracis_SterneG
B.c_group_CA G
B.anthracis_AmesAnc
B.cereus_03BB102
B.anthracis_WestNAG
B.thuringiensis_AlHakamG I
B.cereus_R_3039/03 g B.anthracis_AmesG
B.cereus_E33LG B.cereus_2002734520
B.cereus_ATCC10987G B.cereus_F95/8201g
B.cereus_H3081.97G B.cereus_2000031002
Continued
from B.cereus_F4810/72G B.thuringiensis_BGSC_4AJ1
previous B.c_group_AH819 B.cereus_DSM336
page B.cereus_03BB87 B.cereus_DSM318
B.cereus_G9241G
B.c_group_AH820G
B.cereus_ATCC4342g
B.c_group_AH813
B.c_group_AH1271g
B.c_group_AH818
B.thuringiensis_407
B.cereus_ATCC10876g B.c_group_AH816
B.thuringiensis_HD73 B.thuringiensis_BGSC_4BA1
B.cereus_AH1134G B.thuringiensis_BGSC_4AB1
B.thuringiensis_T04b060 B.cereus_B06_027
B.cereus_172560_Wg II B.cereus_B275
B.thuringiensis_ATCC33679 B.cereus_WG
G
B.cereus_B4264 B.thuringiensis_BGSC_4CC1
B.cereus_ATCC14579G
B.thuringiensis_BGSC_4AY1
B.cereus_R_3149/03
B.cereus_G9842G
B.thuringiensis_ATCC35646G
B.c_group_AH720
B.c_group_AH1272g
B.weihenstephanensis_WSBC10364
B.c_group_AH621g Key:
B.mycoides_WSBC10277 Carries the pXO1 or pBCXO1 plasmid
B.c_group_AH664 Carries a pXO1-like plasmid
B.c_group_AH684 III Carries the pXO2 plasmid
B.weihenstephanensis_KBAB4G Carries a pXO2-like plasmid
B.mycoides_ATCC6462 No pXO1-like or no pXO2-like plasmid identified
B.weihenstephanensis_WSBC10204 xxxG Genome sequence available
B.pseudomycoides_DSM12442 xxxg Genome sequencing underway
B.cereus_cytotoxis_NVH391-98G
Figure 1
Phylogenetic relationships among Bacilli and Bacillus cereus group bacteria. (a) Relationships among a subset of 57 Bacillus species based
on 16S ribosomal DNA (rDNA) sequences. A randomly chosen strain was used to represent each species. Alicyclobacillus acidocaldarius
was used as an outgroup to root the tree. A multiple alignment of 16S rDNA sequences was downloaded from the Ribosomal Database
Project (RDP) Web site (http://rdp.cme.msu.edu/) (11). After removing ambiguously aligned regions and all positions containing
gaps (insertions and deletions), a phylogenetic tree was reconstructed by means of the neighbor-joining method applied to a matrix of
pair-wise distances between sequences. Evolutionary distances were computed using the Tamura and Nei model and MEGA 4.0.2
software (88). (b) Relationships within the B. cereus group. The tree shown is a subtree of 45 isolates extracted from the multilocus
sequence typing (MLST) supertree of 1105 isolates available in the SuperCAT database (http://mlstoslo.uio.no/). The supertree is
based on a combination of the sequence data from all five published MLST schemes for the B. cereus group (see Reference 93 for
details). Roman numerals (I, II, and III) indicate the three main phylogenetic clusters of the B. cereus group population. (c) Relationships
among B. anthracis isolates and close relatives. The tree shown is a subtree of 28 isolates extracted from the MLST supertree of 1105
isolates in the SuperCAT database. The three main evolutionary branches (A, B, and C) within B. anthracis are indicated. In all three
panels members of the B. cereus group are colored according to species. When the species has not been determined, isolates are labeled
“B.c group.” The scale bars are in average numbers of nucleotide substitutions per site.
lambda03
lambda04
4,500,000
B. anthracis
chromosome
5.2 Mbp
lambda02
1,500,000
lambda01
Protein-coding genes of B. anthracis
Chromosomal prophage regions,

3,000,000 anthrax toxin genes, capsule biosynthesis
genes, and associated regulators
Orthologues that have an amino acid
sequence identity above 40%
180,000 1
Orthologues that have an amino acid
sequence identity below 40%
90,000 1
lef
pagR
pagA
B. anthracis
PAI pXO1 plasmid B. anthracis
181.7 kbp pXO2 plasmid
acpA 94.8/96.2 kbp
atxA
cya PAI
capBCADE
acpB

genes encoding these factors and the enterotox- strains isolated from human infections are usu-
ins are located on the chromosome, while the ally not tested for the presence of crystal toxin
genes responsible for the synthesis of the emetic genes or for the production of such toxins.
PLC: phospholipase
toxin are located on a large (270-kb) plasmid, C
pCER270 (15). To date, cereulide production is
limited to two clonal clusters of B. cereus isolates PlcR: A NONFUNCTIONAL
and specific B. weihenstephanensis strains (16, GLOBAL REGULATOR IN
89, 102). The genes coding for the enterotoxin BACILLUS ANTHRACIS
components and degradative enzymes are often Historically, B. anthracis is known for having
also present in strains from the other species of specific phenotypic properties that distinguish
the B. cereus group, including B. anthracis and it from B. cereus, such as being nonmotile, non-
B. thuringiensis strains, suggesting that B. cereus hemolytic, negative for phospholipase C (PLC)
group organisms in general may have the po-
production, and sensitive to γ phage. Several

tential to be pathogenic (26, 30, 56, 74). of these properties are due to a single base
change in the gene encoding the global tran-
scriptional regulator PlcR, which controls most
B. thuringiensis
of the secreted virulence factors in B. cereus and
B. thuringiensis is characterized by its produc- B. thuringiensis.
tion during sporulation of parasporal crystals First described in 1996, PlcR is a pleiotropic
made up of insecticidal proteinaceous toxins regulator that is ubiquitous among isolates in
(Cry and Cyt) (79). The toxins exhibit differ- the B. cereus group (2) and is encoded on
ent specificities toward various classes of in- the chromosome. Whereas plcR usually en-
sects, and B. thuringiensis is the most commonly codes a functional protein in B. cereus and
used biopesticide worldwide (84). The genes B. thuringiensis isolates, a characteristic non-
encoding Cry and Cyt toxins are commonly sense mutation is found in all B. anthracis strains
located on large plasmids, which may be lost, investigated, making the gene dysfunctional (2).
making the bacterium indistinguishable from Although about 1% of non-anthracis B. cereus
B. cereus. So far, no species-specific property group strains carry a plcR gene that is inactivated
outside the plasmid-borne crystal toxin genes by mutations, none of them has the particular
has been identified. mutation found in B. anthracis (82).
B. thuringiensis is an insect pathogen; how- In B. cereus and B. thuringiensis, transcrip-
ever, isolates can act as opportunistic pathogens tion of plcR is activated at the onset of post-
in humans and animals and can cause tissue exponential growth. plcR is part of a two-gene
necrosis, pulmonary infection, or food poison- operon together with papR (62, 81), which en-
ing (19, 31, 56). To what extent this occurs is codes a small protein that is secreted from the
presently not known, because B. cereus group cell and reimported as a processed heptapeptide
←−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−
Figure 2
Whole-genome comparison of Bacillus anthracis and other Bacilli. Proteins orthologous between B. anthracis and other sequenced
Bacillus species were obtained from the Integrated Microbial Genomes (IMG) database (http://img.jgi.doe.gov/cgi-bin/pub/
main.cgi) (53). Orthologues were defined as bidirectional best hits from BLASTP comparisons of B. anthracis and other species, and
were mapped onto circular representations of the B. anthracis chromosome and virulence plasmids pXO1 and pXO2. For the
chromosome and pXO2, the circles are as follows (from the outside): Circle 1, protein-coding genes of B. anthracis; Circle 2, proteins
that have an orthologue in any other sequenced species of the B. cereus group; Circle 3, orthologues shared with any other species of
Bacillus, outside the B. cereus group. For pXO1: Circle 1, protein-coding genes of B. anthracis; Circle 2, proteins that have an orthologue
in the pBCXO1 plasmid of B. cereus G9241; Circle 3, proteins with an orthologue in any other sequenced species of the B. cereus group;
Circle 4, orthologues shared with any other species of Bacillus, outside the B. cereus group. PAI, pathogenicity island.
Cell wall
SecA OppABCDF Translation

Transport
papR Activation
heptapeptide
PapR
?
papR plcR
X
X
Nonsense
PlcR
mutation in
Bacillus anthracis X Regulators
XX
X XX
Secreted Transporters Enzymes Autolysins Environmental

enzymes, sensors
enterotoxins,
and bacteriocins
Figure 3
Schematic overview of the PlcR-PapR quorum-sensing system and the PlcR regulon of Bacillus cereus group
organisms (20). The figure shows translation of the PlcR and PapR proteins from their respective genes (blue
arrows). The PapR protein is exported outside the cell by the SecA secretion machinery and reimported as
a processed heptapeptide through the OppABCDF transport system (black arrows). The PapR heptapeptide
binds the PlcR protein, and the PlcR-PapR complex then activates the transcription ( green arrows) of numerous
genes encoding various functions, many of which constitute virulence factors. PlcR and environmental sensor
proteins also activate secondary transcriptional regulators acting on an unknown set of genes (question mark).
The papR-plcR operon is itself regulated by PapR-PlcR. In B. anthracis the plcR gene contains a nonsense
mutation leading to a nonfunctional protein, and therefore the PlcR regulon is not expressed (red crosses).
(Figure 3) (7, 81), forming a quorum-sensing Deletion of plcR in B. cereus or B. thuringien-

system. PlcR-PapR acts as a transcriptional ac- sis leads to a highly reduced secreted pro-
tivator by binding to a palindromic DNA se- teome (22), and the virulence of plcR strains of
quence (PlcR-box) upstream of its target genes. B. cereus and B. thuringiensis is strongly reduced
Altogether, 28 functional PlcR-boxes have been or abolished in mouse and insect larvae models
identified in the chromosome of B. cereus ATCC (78). The B. anthracis extracellular proteome is
14579 (type strain), forming a regulon of at also highly reduced compared with wild-type
least 45 genes that is under PlcR control (20) B. cereus and B. thuringiensis strains (21). It has
and that encompasses a range of extracellu- been suggested that the ubiquitous nature of the
lar proteins that constitute known or potential plcR mutation in B. anthracis isolates is caused
virulence factors, including the common en- by an incompatibility between the simultane-
terotoxins and degradative enzymes discussed ous presence of the regulon of plcR and of atxA
above (Figure 3). located on pXO1, and sporulation (17, 58), and

the specific plcR mutation has long been re- analysis (AFLP) (32), and multilocus sequence
garded as a principal characteristic differen- typing (MLST) (29, 44, 69, 85, 92). Altogether,
tiating B. anthracis from the other members more than 1500 strains have been mapped
MLEE: multilocus
of the B. cereus group. Whereas B. cereus and by at least one of these three methods, and enzyme
B. thuringiensis strains, which are opportunistic more than 1100 strains have been analyzed by electrophoresis
pathogens, seem dependent on PlcR activity for MLST using any of the five schemes that have AFLP: amplified
virulence, B. anthracis encodes important viru- been developed for the B. cereus group. Of the fragment length
lence properties on its two plasmids, pXO1 and five schemes, which are largely nonoverlapping polymorphism
pXO2, expressed independently of PlcR. When with respect to strain sets and target genes, MLST: multilocus
a functional plcR copy is introduced into B. an- the Tourasse-Helgason and the Priest schemes sequence typing
thracis, expression is detected for several of the are the most comprehensive, and they are
classic virulence factors regulated by PlcR in housed in Web-accessible public databanks
B. cereus and B. thuringiensis, and the B. anthracis [MLSTOSLO (http://mlstoslo.uio.no/) and
PlcR+ strain is hemolytic (58). Toxicity of the PubMLST (http://pubmlst.org/bcereus/)].

B. anthracis PlcR+ strain, however, was not in- In addition, the MLSTOSLO Web site pro-
creased relative to the parental wild-type strain vides access to the SuperCAT database, which
in mouse models of infection, indicating that integrates the complete set of MLST sequences
the PlcR regulon has no effect on B. anthracis and phylogenetic data from each of the five
virulence (58). Thus, the presence of an active typing schemes using supertree methodology,
PlcR is important for the toxicity of B. cereus and and allows the most comprehensive view of the
B. thuringiensis strains, but not for B. anthracis. B. cereus group population to date (93).
The various typing studies have revealed
that B. cereus sensu lato forms a phylogenetic
POPULATION STRUCTURE group in which the members of most species
AND CLASSIFICATION OF THE outside the highly clonal B. anthracis are fre-
BACILLUS CEREUS GROUP quently intermixed (29, 44, 69, 85, 92). Overall,
Two studies conducted in 1952 and 1973 con- the B. cereus group population is divided into
cluded that B. cereus should be considered the three main phylogenetic clusters (Figure 1b),
parent species of the B. cereus group, and the where cluster I contains B. anthracis and related
other taxa as subspecies of B. cereus (24, 83). The B. cereus and B. thuringiensis strains, many of
subspecies recommendations, however, were which are from clinical sources. In addition
not adopted because of criticism from medi- to these clusters, two more distantly related
cal microbiologists and insect pathologists in- clusters form phylogenetically distinct out-
volved in recognizing anthrax and insect dis- groups in the B. cereus sensu lato population.
ease. Later, the B. cereus group was expanded to One includes B. pseudomycoides isolates, and
include two new species: B. weihenstephanensis, the other contains three isolates including
which is cold tolerant (48), and B. pseudomy- B. cereus subsp. cytotoxis, which are the only
coides, which is genetically distinct (Figure 1) known thermophilic members of the B. cereus
(60). group (Figure 1b) (4, 47, 60).
The B. cereus group population appears to
be weakly clonal, showing numerous clonal
Population Structure as Analyzed by complexes emerging from different phyloge-
Molecular Typing Methods netic positions; however, horizontal gene trans-
The population structure of the B. cereus fer and recombination also seem to occur (10,
group has been analyzed by several molecular 85). This population structure, in which a strain
typing methods such as multilocus enzyme of a given species is frequently more closely re-
electrophoresis (MLEE) (28), fluorescent lated to a strain of a different species than to
amplified fragment length polymorphism another strain within its own species, has been
interpreted such that based on genetic crite- been reconstructed using high-resolution typ-
ria alone these bacteria should not belong to ing methods such as multilocus variable number
different species (28). Species status for the six of tandem repeats analysis (MLVA) and single
MLVA: multilocus
variable number of B. cereus group members is kept as is for the nucleotide polymorphism (SNP) mapping (41,
tandem repeats time being, largely due to their widely different 67, 100). The worldwide B. anthracis population
analysis pathotypes and host ranges. is made up of three main phylogenetic branches,
SNP: single named A, B, and C, that differ in evolutionary
nucleotide B. anthracis and B. cereus rates and geographical distribution. In addition,
polymorphism MLVA and MLST have allowed B. cereus and
Clonal Clusters
B. thuringiensis isolates that are close, but not
To date, all known B. anthracis isolates (more
identical, to B. anthracis at the chromosomal
than a thousand) fall into the same clonal group
level to be identified (Figure 1c). B. thuringien-
within the B. cereus group population structure
sis var. pulsiensis CEB02/079, B. thuringiensis
despite their worldwide distribution. Clonal

var. pingluonsis CEB02/074, B. thuringiensis var.

groups of B. cereus and B. thuringiensis strains
monterrey 4AJ1, and B. cereus group isolate
have also been identified. Emetic (cereulide-
2000031002 are among the closest neighbors to
producing) B. cereus strains form two clonal
B. anthracis known to date, as shown by MLVA
clusters, one of which contains more than 30
and/or MLST analyses (8, 54, 96), and may be
worldwide strains (16, 102). In addition, smaller
important to the understanding of B. anthracis
clonal clusters (containing 3 to 12 isolates) were
evolution.
identified for B. thuringiensis var. israelensis (3)
and subsets of B. cereus group isolates origi-
nating from periodontitis patients (27), sam- WHOLE-GENOME SEQUENCING
pled from different patients, time points, and/or OF BACILLUS CEREUS GROUP
countries. While B. anthracis carries pXO1 and STRAINS
the emetic strains carry the cereulide-encoding
The first genome project initiated for a B. cereus
pCER270 plasmid, periodontitis strains map-
group strain, completed in 2003 (74), was that
ping to a clonal cluster harbor a related plas-
of B. anthracis Ames Porton, a plasmid-cured
mid of ∼300 kb, pPER272 (27, 72). Whereas
(pXO1-/pXO2-) variant of a strain originally
pXO1 and pXO2 are virtually identical among
isolated from a dead cow in Texas in 1981.
all B. anthracis isolates, it is currently not known
The first B. anthracis genome to be published,
whether the plasmids shared within a clonal
however, was that of the related strain A2012
B. cereus group are identical, or whether, in
(Ames Florida) (75), which had caused inhala-
the case of strains from periodontal disease
tional anthrax in a Florida photo editor during
and other infections, they contain factors that
the U.S. bioterror attacks in 2001 (40). Cur-
contribute to the development of the disease.
rently, 35 B. cereus group genome sequences are
Clonal clusters of strains causing similar types
publicly available (14 closed, as of January 5,
of infection, however, are not a general feature
2009), and more than 60 additional B. cereus
of the population, as shown for invasive B. cereus
group genomes are in progress, making it one
strains (5), strains associated with gastrointesti-
of the groups of closely related bacteria with
nal illness (34), and isolates causing respiratory
the highest number of sequenced genomes
infections (101).
(http://www.genomesonline.org/) (Table 1).
Differentiating B. anthracis Isolates

and the Identification of B. anthracis B. anthracis
Near-Neighbors In addition to B. anthracis Ames Porton,
Detailed phylogenetic and evolutionary re- the Sterne and Ames Ancestor strains have
lationships among B. anthracis isolates have been sequenced to completion (73; P. Gilna,

unpublished data), and 20 additional B. anthracis that a B. cereus strain (ATCC 10987) was more
genomes have been shotgun-sequenced or are closely related to B. anthracis than to another
in progress, covering all three main branches B. cereus (ATCC 14579). Another discovery
(A, B, and C). A comparison of the various further complicating the relationship between
B. anthracis genome sequences confirmed the B. anthracis and B. cereus resulted from the se-
extreme homogeneity of B. anthracis at the quencing of a B. cereus strain (G9241) that
whole-genome level. The various isolates differ had been isolated from a case of inhalational
only by a limited amount of SNPs, which can anthrax-like disease in a Texas welder (35). This
be used to infer the evolutionary history of the strain, although not among the most closely re-
strains and track the clones for epidemiological lated B. anthracis near-neighbors (Figure 1b),
and forensic purposes (67, 73, 100). Further- carries a 191-kb plasmid (pBCXO1) with 99.6%
more, the genome sequences have highlighted sequence similarity in shared regions, as well
the close relationship of B. anthracis to its rel- as high synteny, to pXO1 and encodes the an-
atives within the B. cereus group; almost all the thrax toxins. B. cereus G9241 is virulent in A/J
putative and known chromosomal B. cereus vir- mice (35) and is a striking example of how re-
ulence factors were also found in B. anthracis sults from genomics have contributed to blur-
(74). Also, a comparative genome hybridiza- ring the borders between the B. cereus group
tion analysis of B. anthracis and 19 B. cereus and species (70). The sequence data collected for
B. thuringiensis strains revealed that 66 to 92% the group are of vast importance to understand-
of the B. anthracis chromosomal genes were ing the relationship between B. anthracis and its
present in a given B. cereus or B. thuringiensis near-neighbors.
strain. Furthermore, homologs to genes from The advent of high-throughput next-
the B. anthracis virulence plasmid pXO1 were generation sequencing technology has opened
found in more than half of the 19 B. cereus and tremendous opportunities for massive paral-
B. thuringiensis isolates investigated, while lel analysis of multiple genome sequences. At
pXO2 genes were less prevalent (74). Only six present, more than 60 B. cereus group genomes
chromosome regions appeared to be unique are under way (http://www.genomesonline.
to B. anthracis, four of which correspond org), including large-scale studies of a set
to excision-proficient, lambdoid prophages of 9 clinical B. cereus isolates from differ-
(lambda01–04) (Figure 2) (74, 86). Although ent types of infections (http://msc.jcvi.org/
phages similar to lambda01 and lambda02 in bacillus cereus/index.shtml) and of 45 iso-
non-anthracis B. cereus group strains were later lates representative of the B. cereus group pop-
identified, none of 108 non-anthracis isolates ex- ulation (T. Read, personal communication). Of
amined contained the full complement of all key interest is also the future release of genome
four elements, whereas all of 192 B. anthracis sequence data from one of the pXO1+/pXO2+
isolates tested did (86). B. cereus group strains (CI and CA) that
were isolated from African great apes, causing
anthrax-like infections (42, 49, 50).
Other B. cereus Group Genomes
Sequencing of the B. cereus type strain ATCC
14579, isolated from a farmhouse in the United pXO1 AND pXO2 PLASMID
States in 1916 (38), and of B. cereus ATCC FAMILIES
10987, a dairy isolate originating from spoiled Among the most influential inputs to the
cheese in Canada in 1930 (71), showed that study of the biology and evolution of B. cereus
B. anthracis and B. cereus genomes generally group organisms have been recent findings of
exhibit a high degree of synteny (conserved B. cereus and B. thuringiensis isolates carrying
Synteny: conserved
gene order). Furthermore, it was shown for the plasmids related to B. anthracis pXO1 and pXO2 gene order
first time at the level of a complete genome (Figure 1b) (18, 64, 65, 71, 72, 98).
Table 1 Genomic features of sequenced genomes from Bacillus anthracis and related Bacillus species
ANRV387-MI63-22
Genome No. of No. of

ARI
Genome GenBank accession size No. of Group I Group II Group I transposase phage
Species/strain Origin/source status numberb (Mbp)c genesc,d intronsc intronsc IStronsc genesc,d genesc,d
B. anthracis Dead cow Finished AE017334, AE017336 5.5 5845 3 2 1 17 72
462
Ames Ancestor (Texas, 1981) (pXO1), AE017335
(A0581/A2084)a (pXO2)
Kolstø
5 August 2009
B. cereus ATCC Farm (United Finished AE016877, AE016878 5.4 5502 0 1 0 28 104
·
14579 States, 1916) (pBClin15)
B. cereus ATCC Dairy cheese Finished AE017194, AE017195 5.4 6114 2 7 3 33 25
Tourasse
10:48
10987 (Canada, (pBc10987)
·
1930)
Økstad
B. cereus G9241 Human Shotgun AAEK00000000, 5.9 6485 1 3 2 81 29
sputum and DQ889680
blood (pBCXO1),
(Louisiana, DQ889679 (pBC210)
1994)
B. thuringiensis Human severe Finished AE017355, CP000047 5.3 5443 2 0 1 61 13
var. konkukian tissue necrosis (pBT9727)
97–27 (Yugoslavia,
1995)
B. thuringiensis Sewage (Israel) Shotgun AAJM01000000 5.9 6229 0 2 2–3e 79 96
var. israelensis
ATCC 35646
B. cereus E33L Dead zebra Finished CP000001, CP000040 5.8 5875 5 5 1 61 39
(formerly (Namibia, (pE33L466),
Zebra Killer) 1996) CP000041 (pE33L5),
CP000042 (pE33L54),
CP000043 (pE33L8),
CP000044 (pE33L9)
B. weihenstepha- Forest soil Finished CP000903, CP000904 5.9 5983 5 0 1 16 77
nensis (France, (pBWB401),
KBAB4 2000) CP000905
(pBWB402),
CP000906
(pBWB403),
CP000907 (pBWB404)
B. thuringiensis Suspected Finished CP000485, CP000486 5.3 4944 1 1 1 20 29

Al Hakam bioweapons facility (pALH1)
ANRV387-MI63-22
(Iraq)
B. cereus subsp. Vegetable puree Finished CP000764, CP000765 4.1 4176 1 2 0 47 47
ARI
cytotoxis (France, 1998) (pBC9801)

NVH391–98
B. cereus Human vomit Shotgun AAUF00000000, 5.5 6266 4 12 2 61 74
AH187 (United Kingdom, DQ889676
(F4810/72) 1972) [emetic] (pCER270)
5 August 2009
B. cereus Human periodontitis Shotgun AAUE00000000, 5.6 6242 4 4 0 42 31

AH820 (Norway, 1995) DQ889677 (pPER272)
B. cereus Human eye Shotgun ABDA00000000, 5.7 6146 2 1 1 29 23
10:48
AH1134 (Oklahoma) ABDA02000035 +

ABDA02000036
(pAH1134 566),
ABDA02000037
(pAH1134 14)
B. cereus Human stool Shotgun ABDJ00000000 5.7 6120 3 4–5e 0 30 78
G9842 (Nebraska, 1996)
B. cereus Human blood and Shotgun ABDI00000000 5.3 5651 1 0 0 25 31
B4264 pleural fluid (1969)
B. cereus Spice mix (Norway, Shotgun ABDK00000000, 5.4 5936 2 0 1 26 44
NVH0597– 1999) ABDK02000071
99 (pNVH0597 60)
B. cereus Dust (Texas, 2003) Shotgun ABDM00000000, 5.9 6529 2 4 1 20 40
03BB108 ABDM02000062
(p03BB108 282),
ABDM02000063
(p03BB108 239),
ABDM02000064
(p03BB108 86),
ABDM02000065
www.annualreviews.org • What Sets Bacillus anthracis Apart from Other Bacillus Species?
(p03BB108 42),
ABDM02000066
463
(p03BB108 10)
(Continued )
ANRV387-MI63-22
ARI
464
Table 1 (Continued )
Kolstø
5 August 2009
·
Genome No. of No. of
Genome GenBank accession size No. of Group I Group II Group I transposase phage
Tourasse
10:48
Species/strain Origin/source status numberb (Mbp)c genesc,d intronsc intronsc IStronsc genesc,d genesc,d
·
B. cereus Food (United Shotgun ABDL00000000, 5.6 6046 3 13–14e 2 82 29
H3081.97 States, 1997) CP001166
Økstad
[emetic] (pH308197 258),
CP001167
(pH308197 11),
CP001168
(pH308197 10),
CP001169
(pH308197 29),
CP001170
(pH308197 73),
CP001171
(pH308197 3)
B. cereus W Soil Shotgun ABCZ00000000, 5.3 5823 2 0 0 7 48
(ATCC ABCZ02000100
11950) (pW 87),
ABCZ02000101
(pW 7),
ABCZ02000102
(pW 3)
a
Twenty-three B. anthracis strains have been or are being sequenced (see http://www.genomesonline.org/). Because B. anthracis isolates are highly monomorphic and virtually identical, data for
the Ames Ancestor strain only are presented in this paper.
b
The first accession number given is that of the chromosome for finished genomes or the full set of sequence contigs for unfinished genomes. Following numbers are for complete plasmids when
applicable (plasmid names are given in parentheses).
c
Including chromosome and plasmids.
d
Not including genes containing frameshifts.
e
Because of incomplete sequence data, the assignment of a few intron fragments to the same or separate elements could not be confirmed.
pXO1 Family been replaced by unique regions in the two

B. thuringiensis plasmids but is simply absent.
A number of B. cereus isolates from clinical,
The backbone shared with pXO2, which cov-
food, or dairy origin carry large plasmids (208– ORF: open reading
ers about two-thirds of pAW63 and pBT9727, is frame
270 kb) that share extended regions (50–80 kb)
essentially composed of genes coding for con-
of sequence homology and synteny with pXO1
jugative, replicative, and regulatory functions,
as well as among themselves (71, 72), but that
as well as mobile elements. A syntenic stretch of
do not contain the 44.8-kb PAI spanning the
16 ORFs weakly similar to the pXO2 backbone
anthrax toxin and regulator genes (61). Instead,
is found in the Enterococcus conjugative plasmid
the B. cereus plasmids frequently contain other
pHTβ, implying that the pXO2 core may have
unique regions: pCER270 carried by emetic
been transferred to or from bacteria outside the
isolates encodes the gene cluster for synthesis of
B. cereus group (91).
the emetic toxin (15), and pPER272 of B. cereus
Five B. cereus and B. thuringiensis strains iso-
periodontitis isolates AH818 and AH820 and

lated from various sources have been shown

pBc10987 from B. cereus ATCC 10987 share a
by PCR or DNA hybridization to encode at
unique region that could play a role in ecolog-
least three of five genes of the pXO2 capsule
ical adaptation (71, 72).
biosynthesis and anchoring cluster (capBCADE)
The regions of similarity between pXO1
(8, 33). All five capsule genes were present and
and the pXO1-like B. cereus plasmids define a
located on a plasmid in one of the isolates,
pXO1 backbone or core, and extensive homol-
B. thuringiensis var. monterrey 4AJ1, an environ-
ogy around the replication origin and in the
mental strain mapping close to the B. anthracis
putative replication protein (RepX) (90) indi-
cluster by MLST (Figure 1b,c). The strain
cates that pXO1 and pXO1-like plasmids form
produces a covalently anchored polyglutamate
a coherent plasmid family (72). Members of
capsule that resembles that of B. anthracis (8).
this family seem to be common to additional
In addition, 10 genes identical in nucleotide
and diverse B. cereus group strains, including
sequence to pXO2, including the full capsule
B. cereus ATCC 43881 and B. thuringiensis var.
operon and the replication genes, have been
kurstaki ATCC 33679, which encode homologs
identified in large plasmids of B. circulans CBD
of at least 50–70 open reading frames (ORFs)
118 and B. acidiceler CBD 119 (52). The above
spanning the entire pXO1 backbone on a large
findings show that the pXO2 capsule gene re-
plasmid of ∼330 kb (64).
gion is shared between B. anthracis and other
Bacilli and thus is not exclusive to B. anthracis.
pXO2 Family
Analogous to pXO1, sequencing efforts have
shown that B. thuringiensis var. kurstaki HD73 B. cereus Strains Carrying pXO1
(from insect host) and B. thuringiensis var. and pXO2
konkukian 97–27 [from severe human tissue Recently, three B. cereus strains, including
necrosis following a gun shot wound (26)] carry G9241, have been discovered and shown to har-
71- to 77-kb pXO2-like plasmids (pAW63 and bor almost the entire pXO1 plasmid, includ-
pBT9727, respectively) that lack the 35-kb PAI ing the anthrax toxin genes and their regula-
of pXO2 (65, 98) and do not contain iden- tors (33, 35). The strains (G9241, 03BB87, and
tifiable virulence factors. The presence of a 03BB102) were responsible for severe or fatal
pXO2 backbone and a highly conserved repli- pneumonias in metal workers from Texas and
cation initiation region and replication pro- Louisiana, with a clinical presentation similar
tein (RepA), however, defines the pXO2 fam- to inhalational anthrax. A perhaps even more
ily, which is part of the pAMβ1 superfamily of striking discovery was that each of the two
gram-positive unidirectional theta-replicating B. cereus group strains, CI and CA, carries two
plasmids. Unlike pXO1, the pXO2 PAI has not plasmids with high identity to B. anthracis pXO1
and pXO2 (S. Klee, personal communication). with the genetic relationships among the strains
These strains were recovered from great apes as assessed by chromosomal phylogenies using
(nine chimpanzees and one gorilla) that had AFLP, MLEE, or MLST. Like B. anthracis,
died from anthrax-like disease in tropical rain- the majority of the known non-anthracis iso-
forests in the Ivory Coast (CI) and Cameroon lates harboring pXO1-like and/or pXO2-like
(CA) (42, 49, 50). The pXO1 and pXO2 plas- plasmids do belong to main cluster I of the B.
mid in these strains contains the anthrax toxin cereus group population, such as B. thuringiensis
genes and the polyglutamate capsule biosyn- var. konkukian 97–27 (carrying pBT9727)
thesis genes, respectively, along with the asso- and B. cereus AH820 and AH818 (pPER272)
ciated regulatory genes (atxA, acpA, and acpB) (Figure 1b) (8, 92). B. cereus G9241 and 03BB87
(42), demonstrating that even the simultane- (pBCXO1), however, branch much farther
ous presence of all these determinants is not away from B. anthracis than B. cereus E33L,
unique to B. anthracis and therefore does not which does not possess pXO1- or pXO2-
suffice to differentiate B. anthracis from other like elements (33). B. cereus ATCC 43881,
B. cereus group members. Indeed, the isolates B. thuringiensis var. kurstaki ATCC 33679 (both
from the great apes were originally identified carry pXO1-like plasmids), and B. thuringiensis
as B. anthracis on the basis of pathology, cytol- var. kurstaki HD73 (pAW63) belong to main
ogy, and molecular investigations using PCR cluster II (32, 64, 65). Furthermore, the phy-
and variable number of tandem repeats analy- logeny of the plasmids, based on genes from the
sis (49). However, further genotyping and mi- conserved core, is inconsistent with the chro-
crobiological and functional characterization, mosomal phylogeny; pPER272 is, for example,
as well as MLST-based phylogenetic analysis, significantly more similar to pCER270 and
revealed that they are distinct from classical pBc10987 than to pXO1/pBCXO1 (72). The
B. anthracis (Figure 1b) (42, 50). sporadic and conflicting distribution of pXO1-
The sequence of the plcR regulator of and pXO2-like plasmids can be explained by
B. cereus G9241, as well as that of the CI and horizontal transfer of plasmids between B.
CA strains, does not contain the nonsense mu- cereus group isolates, which is well known (see
tation typical of B. anthracis. PlcR is predicted Dynamics of Bacillus cereus Group Genomes,
to be functional in B. cereus G9241 because it ex- below). To exchange DNA, bacteria must
presses genes from the PlcR regulon (35). Also, be in the same environment. Therefore, it is
this isolate carries an atxA gene virtually identi- interesting that several B. cereus strains carrying
cal to that of B. anthracis, which raises questions a plasmid with striking similarity to pXO1 (e.g.,
whether the concomitant presence of the AtxA pBCXO1) were collected in the same geograph-
and PlcR regulators, and the sporulation pro- ical area (Texas and Louisiana) where anthrax is
cess, is incompatible (58). Possibly, the incom- endemic (33), possibly suggesting that B. cereus
patibility may be restricted to the B. anthracis isolates may have acquired plasmid DNA from
lineage. plcR in the CI and CA strains, however, B. anthracis in this area. The mobile nature of
has a 1-bp insertion in the 3 end, introducing the B. cereus group plasmids emphasizes the
a frameshift and a four-amino-acid extension importance of applying chromosomal markers
in the C terminus. Whether this PlcR is func- to phylogenetic and evolutionary studies of
tional is not yet known; however, the CI and B. anthracis and its relatives.
CA strains are nonhemolytic and do not express
PLC (42; S. Klee, personal communication). DYNAMICS OF BACILLUS CEREUS
GROUP GENOMES
Plasmid Distribution and
Plasmids and Phages
Chromosomal Relationships
The distribution and similarity of plasmids in B. cereus group organisms have numerous mo-
the B. cereus group do not generally correlate bile genetic components indicative of a dynamic

genome. Indeed, direct evidence for plasmid of the PAI, however, is not obvious, as some of
transfer by conjugation among B. thuringien- the genes within the PAI are conserved in other
sis strains or between B. thuringiensis and B. cereus group plasmids not carrying the island
Insertion sequence
B. cereus or B. mycoides has been observed both (37, 64). Among the transposons, TnXO1 car- (IS) element: short
in laboratory cultures and in natural environ- ries the gerX genes, involved in the germination (0.7- to 2.5-kb) mobile
ments (23, 36, 76, 99, 103). pXO1 and pXO2 of B. anthracis spores in macrophages in a mouse DNA element
are not self-transmissible, but they can be trans- anthrax model (25). TnXO1 has been found in generally carrying one
or two transposase
ferred to B. anthracis and B. cereus with the help full in B. anthracis pXO1 (97), but, as for IS1627,
genes that are
of a conjugative mobilization plasmid, such as also in the highly similar pBCXO1 carried by responsible for
pXO12 or pXO14 from B. thuringiensis (76). particular B. cereus strains. mobility; also known
Thus, there is no genetic isolation of B. an- Group I and group II introns are two dif- as class I transposons
thracis and the other B. cereus group species with ferent types of self-splicing and mobile RNA Transposon: long (4-
respect to plasmid DNA exchange. The same is elements that interrupt genes (6). The dis- to 25-kb) mobile DNA
true for phage transmission; the γ phage infect- tribution and evolution of introns in 29 se- element with a usually
complex structure,
ing B. anthracis, originally isolated from B. cereus quenced B. cereus group genomes (including 11
carrying transposase
W, and the transducing bacteriophage CP-51 B. anthracis isolates) have been reviewed re- and resolvase genes for
are well-known examples of cross-species infec- cently (94), revealing a high diversity and mobility, as well as
tions (54, 55, 80). Furthermore, the fact that the variability. While B. anthracis isolates are accessory passenger
B. anthracis lambda01 prophage is present in the monomorphic and all harbor three group I genes specifying
unrelated functions;
chromosomes of B. cereus E33L and B. weihen- introns in the chromosome and two group II
also known as class II
stephanensis KBAB4 indirectly suggests infec- introns in pXO1, B. cereus, B. thuringiensis, and transposons
tion and chromosomal integration by the same B. weihenstephanensis strains can harbor from 0
or a related phage (Figure 2) (70, 94). Similarly, to 5 group I elements, and from 0 to 13 group
lambda02-specific sequences have been identi- II elements (Table 1). There is no correlation
fied in several non-anthracis strains (Figure 2) between intron content or sequence similarity
(86). and strain origin or species (94). Also, like most
B. cereus group strains, the B. anthracis chro-
mosome harbors a 1.9-kb composite element
Other Mobile DNA and BcISt1 (92). BcISt1 is an IStron consisting of
RNA Elements a self-splicing group I intron associated with
B. cereus group organisms also contain a diverse an IS element, thus combining splicing ability
range of other mobile and repeated elements with mobility. Nearly all BcISt1 insertion loci
that contribute to genome dynamics and that are unique to a given B. cereus group strain (con-
may also have phenotypic impact, including sidering all B. anthracis isolates as one) (92).
insertion sequence (IS) elements, transposons, A comparison of the intergenic regions
group I and group II introns, IStrons, and pu- of 16 B. cereus group genomes, including 10
tatively mobile repeated DNA sequences. The B. anthracis strains, revealed the presence of a
genetic features and distribution of specific IS common pool of 18 groups of 100- to 400-bp
elements (e.g., IS231, IS232, IS240, ISBT1, interspersed repeated DNA sequences, termed
and ISBT2) and transposons (e.g., Tn4430, bcr1–bcr18 (92). Mobility has been suggested
Tn5401, and TnXO1) have been examined (51, for bcr1 (43, 63). Two types of bcr repeats are
97). These elements are found in the various represented: (a) sequences that are present in
members of the B. cereus group, and none is multiple copies in the various strains and that
specific to B. anthracis. The pXO1 PAI is bor- are found in diverse genomic locations (bcr1–
dered by inverted copies of IS1627, which is 6; bcr1–3 present in 15–80 copies per genome);
probably responsible for its inversion in some and (b) homologous intergenic regions present
B. anthracis isolates (75). Whether these IS1627 in corresponding loci in all strains (bcr7–18).
copies have been implicated in the acquisition Virtually all repeats are ubiquitously present in
all the B. cereus group genomes examined, in- At least two of the four prophages
cluding B. anthracis, and there is no species- integrated into the B. anthracis chromo-
specific pattern of genomic location or DNA some have been found in other B. cereus
sequence. Twelve sets of repeats appeared to be group strains (86).
unique and specific to the B. cereus group of bac- No chromosomal genes outside the
teria and can be considered as a common fea-
prophages are specific to B. anthracis (74),
ture unifying the B. cereus group as a cohesive
and no chromosomal signature sequences
population (92).
that can be used to distinguish B. anthracis
The common message is that, like for plas-
from the other B. cereus group members
mids and phages, there is no pattern or feature
have been identified.
in the IS elements, transposons, introns, or in-
terspersed sequence repeats, setting B. anthracis Furthermore, application of high-resolution
apart from the other B. cereus group species. Un- molecular typing techniques such as MLST
like several other bacteria, in which mobile ele- and MLVA has led to the identification of
ments such as IS and other repeated sequences several near-neighbor strains that share sev-
take part in major genome rearrangements, no eral alleles with B. anthracis. Therefore, what
such contributions have so far been observed in at present remains to principally differentiate
the highly syntenic B. cereus group genomes. the B. anthracis lineage from the rest of the
B. cereus group at the genetic level are the fol-
lowing three characteristics, all of which are im-
CONCLUSIONS AND FUTURE posed by chromosome-encoded factors: (a) be-
RESEARCH ing part of the clonal cluster made up of highly
The Species: What is in a Name? monomorphic B. anthracis strains, as analyzed
by MLST, MLVA or similar methods; (b) car-
The establishment during the past decade of rying the nonsense mutation at nucleotide po-
methodology allowing gene-based phylogenies sition 640 of the plcR gene, introducing a pre-
and whole-genome sequencing of a multi- mature TAA stop codon; and (c) the presence
tude of strains from the B. cereus group has of a full complement of the four chromosomal
changed the view of the relationship between lambdoid prophages.
B. cereus group organisms. Explanations have The concept of a species for asexual prokary-
been provided in molecular terms for some of otic organisms (Bacteria and Archaea) has been
the classical phenotypic differences separating the subject of extensive discussions. The crite-
B. anthracis from the rest of the population, ria used for defining bacterial species have been
such as the lack of hemolytic activity and se- changing and updated over time, particularly
creted enzymes caused by the nonsense muta- in light of genome sequencing projects, which
tion in plcR. Furthermore, many genotypic and have shown that there can be a high genotypic
phenotypic characteristics previously thought diversity between strains of the same species
to be specific for B. anthracis are not unique but and that homologous recombination and lat-
may be shared by isolates of other species in the eral gene transfer are major forces driving bac-
group: terial evolution. Various concepts have been
Virulence plasmids pXO1 and pXO2 suggested for microbial species, but none has
are occasionally found in other B. cereus been generally accepted, and a new integra-
group isolates (33, 42, 72, 98). tive concept has recently been introduced by
plcR is found in an inactive form also in Achtman & Wagner (1), who propose that
some B. cereus and B. thuringiensis strains, bacterial species should be defined as metapop-
although with mutations different from ulation lineages, i.e., cohesive groups of pop-
those in the B. anthracis lineage (82). ulations that undergo the same evolution-
Sensitivity to γ phage is not exclusive (54). ary forces. In this respect, although B. cereus

group organisms could be regarded genetically significantly slower evolutionary rate than the
and genomically as one species (28, 70), the other B. anthracis strains, suggesting that they
monomorphic B. anthracis lineage should most are less fit as pathogens owing to the loss of
likely be kept as a separate species. In our opin- virulence (67, 100).
ion, the species name B. anthracis should be Strains of the B branch are also less fre-
reserved for this lineage. Therefore, B. cereus quent, mostly found in South Africa and France,
group strains carrying pXO1 and pXO2 but that whereas the A branch seems to have undergone
do not belong to the B. anthracis evolutionary a massive evolutionary radiation and global
line, such as the CI and CA strains (42, 49, 50), spread in its development into a successful
should not be called B. anthracis, in spite of hav- pathogen. These A-B differences may possi-
ing both virulence plasmids and exhibiting an bly be related to the SNPs separating these
anthrax-like pathotype. Rather, we suggest des- branches (100). In addition, several insertions/
ignating such strains B. cereus var. anthracis. This deletions that we identified by comparison of
should also be applied to strains such as B. cereus protein sequence sets of A and B branch strains
G9241, which carries pBCXO1 and produces could be of importance. Altogether 35 chro-
an alternative capsule (35). mosomally encoded proteins had a different
length in the two branches, most of them were
of only 1 or 2 amino acids, while three pro-
pXO1 and pXO2: Key Players teins had a difference of 10 amino acids or
in the Evolution Toward a more: GBAA0489 (arginine utilization protein
Monomorphic Lineage? RocR, 32-amino-acid deletion specific to the
The key elements of B. anthracis as the cause B branch); GBAA2790 (ferredoxin, 18-amino-
of anthrax are the presence of the anthrax toxin acid deletion specific to the A branch); and
genes and the capsule synthesis genes on the GBAA4182 (pyruvate dehydrogenase complex
pXO1 plasmid and pXO2 plasmid, respectively. e2 component, dihydrolipoamide acetyltrans-
Still, in evolutionary terms, perhaps the prime ferase, 10-amino-acid deletion specific to the A
characteristic and most striking feature of B. an- branch). Of the shorter protein variations, 19
thracis is its development as a monomorphic lin- of 32 are found in hypothetical genes for which
eage. This apparently strict development may no functional information is available.
be due to coevolution of the chromosome and It is probable that other B. cereus group
pXO1 and pXO2, following acquisition of the species with an active PlcR are better equipped
virulence plasmids. Evidence for tight coevo- than B. anthracis to survive and compete out-
lution is given by the complex regulatory net- side the mammalian host in the absence of
works and cross-talks linking numerous chro- the two virulence plasmids. Whether success-
mosomal and plasmidic loci, as exemplified by ful coevolution between chromosome and plas-
the AtxA regulon (17, 57, 68). As B. anthracis mid(s) involving adaptation to particular envi-
is a recently emerged pathogen, with an esti- ronmental niches may also occur in B. cereus and
mated origin in the Holocene period (12,000– B. thuringiensis strains is still open for inves-
26,000 years ago) (100), the timescale of this tigation, but emetic and periodontal strains
coevolution appears to have been relatively form clusters of isolates that are clonal at
short in evolutionary terms. During this time, the chromosomal level and carry related plas-
however, the chromosome-plasmid coevolu- mids of similar sizes, several of which contain
tion has made B. anthracis well suited for survival pXO1-related genes (16, 27, 102). To what ex-
in its niche—mammals. Indeed, the B. anthracis tent plasmid-chromosome coevolution has oc-
isolates belonging to the phylogenetically di- curred, or is occurring, in the CI and CA strains,
vergent C branch, which lack the pXO1 plas- and whether pXO1 and pXO2 are equally sta-
mid, are rare in nature (only two isolates are bly maintained in these strains as in B. anthracis,
known to date). Also, they appear to exhibit a is yet not known. These strains present many
phenotypes similar to B. anthracis isolates, ex- in other B. cereus group genomes, and two-
hibiting an anthrax-like pathotype, being non- thirds of these genes code for hypothetical pro-
hemolytic, not expressing PLC, carrying pXO1 teins. The impact of these genes on the biol-
and pXO2, and producing the protective anti- ogy of B. cereus group bacteria is still unknown.
gen and a capsule (42, 49, 50). However, CI and Also, gene loss may be key to pathogenicity
CA map outside the B. anthracis cluster by chro- development, as for other bacterial species. A
mosomal phylogeny and carry a different plcR few genes that are present in all sequenced
mutation, showing that organisms with most B. cereus and B. thuringiensis chromosomes are
or all B. anthracis–characteristic features neces- lacking in B. anthracis. These are BC3663, a
sary to cause anthrax or anthrax-like disease in a transporter (drug/metabolite exporter family);
mammal may arise independently, separated in BC3664, a peptidase of the M20/M25/M40
space and time. The current genetic picture of family (N-acyl-l-amino acid amidohydrolase);
the CI and CA strains, however, could be tran- and BC5034, a methyl-accepting chemotaxis
sient and thus represent a snapshot in evolution. protein. Whether the loss of these genes has
Conversely, if the plasmids and the CI-/CA- been of importance for the development of
specific plcR mutation are stably maintained, it B. anthracis as a pathogen is not known. Modi-
is possible that these strains have undergone a fied expression levels of key genes may also be
different path of chromosome-plasmid coevo- of importance.
lution than B. anthracis sensu stricto. It is not Finally, during B. anthracis evolution, genes
unconceivable that more strains similar to CA originally supporting housekeeping functions
and CI may be discovered in the future, demon- may have been adapted for functions linked to
strating the need to include chromosomal phy- pathogenicity; the key virulence factors are only
logeny methods when describing new isolates expressed in the presence of bicarbonate and a
causing anthrax-like disease. functional atxA gene. B. anthracis employs an
Most of the research on B. anthracis has ABC transporter (BAS2714-12) for the trans-
been aimed at understanding the pathogenic- port of bicarbonate, and this locus is essen-
ity of the bacterium, and a complex regulatory tial for B. anthracis toxicity in a mouse model
network involving the plasmid-borne virulence (68). This gene locus is present in all sequenced
genes has been characterized (17, 68). Only a B. cereus group strains. Whether its function is
minor part of the pXO1 and pXO2 genes, 22% unique to the B. anthracis lineage, or whether
and 23%, respectively, have a predicted func- it is important for virulence in strains such as
tion. More than half of the genes are found B. cereus G9241, CI, and CA, is unknown.
SUMMARY POINTS
1. B. anthracis is highly monomorphic, constituting a separate lineage of the B. cereus group.
2. Several B. cereus group strains outside the B. anthracis species harbor plasmids with
stretches of high similarity to the pXO1 and pXO2 plasmids (pXO1 and pXO2 plas-
mid families), but these plasmids usually do not contain the anthrax toxin genes or the
genes for capsule synthesis.
3. The main virulence factors, the two plasmids containing the B. anthracis toxin genes
(pXO1) and genes for the synthesis of capsule (pXO2), are also found in certain strains
of other B. cereus group members.
4. B. anthracis carries the same general virulence genes in the chromosome as its closest
relatives, B. cereus and B. thuringiensis, but these genes are not expressed in B. anthracis
because of a mutation in the global regulator PlcR. Thus, in most cases B. anthracis is

phenotypically easily distinguishable from its close relatives; however, B. cereus and
B. thuringiensis strains exist that have a defect PlcR gene and thus may exhibit a
B. anthracis–like phenotype.
5. The following characteristics set B. anthracis apart from its nearest neighbors: (a) being
part of a separate and unique evolutionary lineage within the B. cereus group; (b) carrying
the characteristic mutation in the plcR gene, rendering the PlcR regulon inactive; and
(c) presenting a full complement of four prophages (lambda01-lambda04) within the
chromosome.
6. We hypothesize that B. anthracis has evolved successfully as a monomorphic lineage
because of strict coevolution involving both the chromosome (including the characteristic
PlcR mutation) and the two plasmids pXO1 and pXO2.
7. It remains to be seen whether the newly discovered B. cereus strains isolated from African
great apes, which contain both a full pXO1 and pXO2 and include toxin and capsular
synthesis genes, are examples of successfully established and stable variants of the B. cereus
group. We suggest the nomenclature B. cereus var. anthracis for B. cereus group strains that
harbor pXO1 (or pBCXO1) and pXO2 (or produces an alternative capsule), but that do
not belong to the B. anthracis lineage by chromosomal molecular phylogeny analysis.
FUTURE ISSUES
1. The most exciting discoveries during the past five years pertain to the presence of fully
virulent pXO1 and/or pXO2 plasmid(s) in B. cereus strains exhibiting B. anthracis–like
phenotypes. An important line of research should therefore involve further analysis of
such strains, including the investigation of plasmid stability and PlcR function.
2. What will the genome sequences of the B. cereus CA and CI strains (var. anthracis) from
African great apes reveal about the biology of these isolates? (One strain is sequenced
and soon to be released.) Sequencing should be followed by functional analyses of these
strains.
3. Do more B. cereus var. anthracis strains exist in Africa? Are such strains more common
than we think?
4. Likewise, are there reservoirs of B. cereus strains with the pXO1 plasmid in areas endemic
for anthrax (e.g., Texas, Louisiana, or Kruger National Park, South Africa)?
5. To increase our knowledge and understanding of the pXO1 and pXO2 plasmid families
and their evolution, more pXO1- and pXO2-related plasmids should be sequenced.
6. What are the functions of the large number of hypothetical genes—both on the chro-
mosome and on the pXO1 and pXO2 plasmids (and other plasmids in these families),
and what contributions do they make to the biology of B. anthracis and the other B. cereus
group bacteria?
DISCLOSURE STATEMENT
The authors are not aware of any affiliations, memberships, funding, or financial holdings that
might be perceived as affecting the objectivity of this review.
ACKNOWLEDGMENTS
We thank Agnès Fouet (Pasteur Institute) for critical reading of the manuscript. ABK, NJT, and
OAØ are supported by project grants from the Norwegian Research Council, a Strategic Univer-
sity Program (SUP, project number 146534/420), the FUGE technology platform Consortium
for Advanced Microbial Sciences and Technology (FUGE-CAMST, project number 152020/310),
and a FUGE II Channel 3 grant (project number 183421). All authors contributed equally to this
review.
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AR387-FM ARI 5 August 2009 13:23
Annual Review of
Microbiology
Contents Volume 63, 2009
Frontispiece
Lars G. Ljungdahl p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p xii
A Life with Acetogens, Thermophiles, and Cellulolytic Anaerobes

Lars G. Ljungdahl p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 1
Regulation of Translation Initiation by RNA Binding Proteins
Paul Babitzke, Carol S. Baker, and Tony Romeo p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p27
Chemotaxis-Like Regulatory Systems: Unique Roles
in Diverse Bacteria
John R. Kirby p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p45
Aminoacyl-tRNA Synthesis and Translational Quality Control
Jiqiang Ling, Noah Reynolds, and Michael Ibba p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p61
Resurrected Pandemic Influenza Viruses
Terrence M. Tumpey and Jessica A. Belser p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p79
Interspecies Chemical Communication in Bacterial Development
Paul D. Straight and Roberto Kolter p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p99
Lipid Signaling in Pathogenic Fungi
Ryan Rhome and Maurizio Del Poeta p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 119
Biological Insights from Structures of Two-Component Proteins
Rong Gao and Ann M. Stock p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 133
Role of GTPases in Bacterial Ribosome Assembly
Robert A. Britton p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 155
Gene Transfer and Diversification of Microbial Eukaryotes
Jan O. Andersson p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 177
Malaria Parasite Development in the Mosquito and Infection
of the Mammalian Host
Ahmed S.I. Aly, Ashley M. Vaughan, and Stefan H.I. Kappe p p p p p p p p p p p p p p p p p p p p p p p p p p p p 195
How Sweet it is! Cell Wall Biogenesis and Polysaccharide Capsule
Formation in Cryptococcus neoformans
Tamara Lea Doering p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 223
v
Mitochondrial Evolution and Functions in Malaria Parasites

Akhil B. Vaidya and Michael W. Mather p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 249
Probiotic and Gut Lactobacilli and Bifidobacteria: Molecular
Approaches to Study Diversity and Activity
Michiel Kleerebezem and Elaine E. Vaughan p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 269
Global Emergence of Batrachochytrium dendrobatidis and Amphibian
Chytridiomycosis in Space, Time, and Host
Matthew C. Fisher, Trenton W.J. Garner, and Susan F. Walker p p p p p p p p p p p p p p p p p p p p p p p p p 291
Anaerobic Oxidation of Methane: Progress with an Unknown Process
Katrin Knittel and Antje Boetius p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 311

The Trypanosoma brucei Flagellum: Moving Parasites

in New Directions
Katherine S. Ralston, Zakayi P. Kabututu, Jason H. Melehani,
Michael Oberholzer, and Kent L. Hill p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 335
Plants, Mycorrhizal Fungi, and Bacteria: A Network of Interactions
Paola Bonfante and Iulia-Andra Anca p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 363
Evolutionary Roles of Upstream Open Reading Frames in Mediating
Gene Regulation in Fungi
Heather M. Hood, Daniel E. Neafsey, James Galagan, and Matthew S. Sachs p p p p p p p p p 385
Single-Cell Ecophysiology of Microbes as Revealed by Raman
Microspectroscopy or Secondary Ion Mass Spectrometry Imaging
Michael Wagner p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 411
Microbiology of the Atmosphere-Rock Interface: How Biological
Interactions and Physical Stresses Modulate a Sophisticated
Microbial Ecosystem
Anna A. Gorbushina and William J. Broughton p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 431
What Sets Bacillus anthracis Apart from Other Bacillus Species?
Anne-Brit Kolst, Nicolas J. Tourasse, and Ole Andreas Økstad p p p p p p p p p p p p p p p p p p p p p p p p p p p 451
The Expanding World of Methylotrophic Metabolism
Ludmila Chistoserdova, Marina G. Kalyuzhnaya, and Mary E. Lidstrom p p p p p p p p p p p p p p 477
Genomics, Genetics, and Cell Biology of Magnetosome Formation
Christian Jogler and Dirk Schüler p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 501
Predatory Lifestyle of Bdellovibrio bacteriovorus
Renee Elizabeth Sockett p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 523
Plant-Growth-Promoting Rhizobacteria
Ben Lugtenberg and Faina Kamilova p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 541
vi Contents
Photorhabdus and a Host of Hosts

Nick R. Waterfield, Todd Ciche, and David Clarke p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 557
Management of Oxidative Stress in Bacillus
Peter Zuber p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 575
Sociobiology of the Myxobacteria
Gregory J. Velicer and Michiel Vos p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 599
Index
Cumulative Index of Contributing Authors, Volumes 59–63 p p p p p p p p p p p p p p p p p p p p p p p p p p p 625

Errata
An online log of corrections to Annual Review of Microbiology articles may be found at

http://micro.annualreviews.org/
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What Sets Bacillus Anthracis Apart From Other Bacillus Species?

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ANRV387-MI63-22 ARI 5 August 2009 10:48

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Annu. Rev. Microbiol. 2009. 63:451–76 Key Words

The Annual Review of Microbiology is online at Abstract

AND CLASSIFICATION OF THE DYNAMICS OF BACILLUS CEREUS

BACILLUS CEREUS GROUP . . . . . 459 GROUP GENOMES . . . . . . . . . . . . . 466

INTRODUCTION of the disease, with high lethality. B. anthracis

452 Kolstø · Tourasse · Økstad

BACILLUS SPECIES phenotypic traits of the B. cereus group species

454 Kolstø · Tourasse · Økstad

b B. cereus group c B. anthracis neighbors

Protein-coding genes of B. anthracis

Chromosomal prophage regions,

456 Kolstø · Tourasse · Økstad

production, and sensitive to γ phage. Several

SecA OppABCDF Translation

Secreted Transporters Enzymes Autolysins Environmental

(Figure 3) (7, 81), forming a quorum-sensing Deletion of plcR in B. cereus or B. thuringien-

458 Kolstø · Tourasse · Økstad

PlcR+ strain is hemolytic (58). Toxicity of the PubMLST (http://pubmlst.org/bcereus/)].

despite their worldwide distribution. Clonal

var. pingluonsis CEB02/074, B. thuringiensis var.

Differentiating B. anthracis Isolates

460 Kolstø · Tourasse · Økstad

Genome No. of No. of

10987 (Canada, (pBc10987)

B. thuringiensis Suspected Finished CP000485, CP000486 5.3 4944 1 1 1 20 29

cytotoxis (France, 1998) (pBC9801)

B. cereus Human periodontitis Shotgun AAUE00000000, 5.6 6242 4 4 0 42 31

AH1134 (Oklahoma) ABDA02000035 +

pXO1 Family been replaced by unique regions in the two

periodontitis isolates AH818 and AH820 and

lated from various sources have been shown

466 Kolstø · Tourasse · Økstad

468 Kolstø · Tourasse · Økstad

470 Kolstø · Tourasse · Økstad

472 Kolstø · Tourasse · Økstad

474 Kolstø · Tourasse · Økstad

whereas the B and C

FEMS Microbiol. Rev. 29:303–29 branches are more rare

B. thuringiensis). Nucleic Acids Res. 36:D461–68

476 Kolstø · Tourasse · Økstad

Contents Volume 63, 2009

A Life with Acetogens, Thermophiles, and Cellulolytic Anaerobes

Mitochondrial Evolution and Functions in Malaria Parasites

Katrin Knittel and Antje Boetius p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 311

The Trypanosoma brucei Flagellum: Moving Parasites

Photorhabdus and a Host of Hosts

Cumulative Index of Contributing Authors, Volumes 59–63 p p p p p p p p p p p p p p p p p p p p p p p p p p p 625

An online log of corrections to Annual Review of Microbiology articles may be found at

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