Anthrax (Bacillus anthracis), Molecular Biology of
311
2
The Virulence Plasmids
A gapped, linear sequence of approxi-
mately
93 kbp
has
been
generated
for
pXO2,
but
a
detailed
analysis
of
the
sequence
has
not
yet
been
published.
Comparison of the pXO2 sequences from
various
B. anthracis
isolates identiFed sev-
eral variable pXO2 markers, leading to the
suggestion that this plasmid is the source
of much of the variability in the
B. anthracis
genome. More work needs to be done be-
fore the functions of the gene products
encoded by this plasmid are discovered.
The 181-kbp pXO1 plasmid has been
fully sequenced. It has 143 predicted open
reading frames, most encoding proteins of
unknown function. There are also several
pXO1-associated phenotypes that have not
been assigned to a particular gene. Among
these phenotypes are different nutritional
requirements, altered sensitivity to bacte-
riophages, and escape of
B. anthracis
from
cultured macrophages.
The most striking feature of this plas-
mid is a 44-kbp region that has been
designated a pathogenicity island (±ig. 2).
These islands are large regions of DNA
that confer virulence phenotypes and are
believed
to
have
been
acquired
from
unrelated organisms. The pathogenicity is-
land of pXO1 contains 31 predicted open
reading frames, including all three toxin
genes and their regulatory elements. It
is flanked by two inverted and nearly
identical copies of an insertion sequence
element that serve as footprints for previ-
ous transposition of DNA. Also, within
the
island
are
genes
encoding
trans-
posases and integrases – enzymes that are
involved in the movement of DNA seg-
ments – which, along with the insertion
sequences, suggest that there may be plas-
ticity to this region. In fact, comparative
restrictionanalysisofthisregionindiffer-
ent
B. anthracis
isolates indicates that the
pathogenicity island is inverted in some
strains.
The origin of this pathogenicity island
is
unclear,
if,
in
fact,
it
did
come
from
another
species.
One
possibility
is
that
it
came
from
a
member
of
the
Bacillus
cereus
phylogenetic
group,
to which
B. anthracis
belongs, as some
of the insertion sequence elements in
the pathogenicity island are very similar
to those isolated from other members
of this group. ±urther supporting this
hypothesis is the fact that the GC content
of the pathogenicity island does not differ
signiFcantly
from
that
of
the
rest
of
lef
pagR pagA
Insertion sequence elements
Known virulence factors
Transposases, integrases
Other genes
gerXC gerXA gerXB
atxA
cya
Fig. 2
The pathogenicity island of
B. anthracis
.
Depicted is the basic structure of the
pathogenicity island that is located on the pXO1
plasmid. It encodes, among other things, a
major virulence gene regulator (
atxA
), the
anthrax toxin proteins (
pagA
,
lef
,
cya
), and an
operon involved in sporulation (
gerXA
,
gerXB
,
and
gerXC
). Adapted from Okinaka, R.T., Cloud,
K., Hampton, O., Hoffmaster, A.R., Hill, K.K.,
Keim, P., Koehler, T.M., Lamke, G., Kumano, S.,
Mahillon, J., Manter, D., Martinez, Y., Ricke, D.,
Svensson, R., Jackson, P.J. (1999) Sequence and
organization of pXO1, the large
Bacillus anthracis
plasmid harboring the anthrax toxin genes,
J. Bacteriol.
181
, 6509–6515.
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