Anthrax (Bacillus anthracis), Molecular Biology of
319
Owing
to
the
monomorphic
nature
of the
B. anthracis
genetic composition,
direct
sequence
comparisons
between
isolates are the most effective method for
distinguishing related strains. Even with
this complete sequence comparison, it is
not possible to distinguish between all
isolates, as indicated by the difFculty in
distinguishing between various isolates of
the Ames strain.
4
Regulation of Virulence
As mentioned above, the major virulence
factors
for
B. anthracis
are
a
poly-D-
glutamic acid capsule and the anthrax
toxin. Synthesis of the capsule requires
four genes:
capA, capB, capC
,an
d
dep
(capD)
. The toxin, composed of protective
antigen, edema factor, and lethal factor, is
encoded by
pagA, cya
,and
lef
respectively.
The
genes
encoding
these
factors
are
expressed in a regulated fashion, through
the action of two major regulators, AtxA
and AcpA, but additional regulatory factors
are also involved. A Fgure summarizing
the
virulence
regulation
pathways
in
B. anthracis,
as we currently understand
them, is shown in ┬▒ig. 6.
4.1
AtxA
The toxin genes and
atxA
are expressed
by
vegetative
cells
shortly
after
spore
germination
in
cultured
macrophages.
Expression of
atxA
at this time is important
because it is essential for the release of
the bacteria from macrophages. The
atxA
gene is located on pXO1 between the
cya
and
pagA
genes. In
atxA
+
strains,
the toxin genes are coexpressed, and this
expression is enhanced by elevated CO
2
levels and temperature, with induction at
lef
CO
2
CO
2
CO
2
CO
2
CO
2
pagR
pagA
acpA
capD
pXO2
pXO1
capA capC capB
gerXC
abrB
gerXA
gerXB
atxA
cya
?
Environment
Temperature
Environmental signal
Gene sequence
Activation
Inhibition
Fig. 6
Regulation of plasmid-encoded virulence gene expression. This Fgure is an
overview of regulatory pathways known to be involved in
B. anthracis
virulence gene
expression. Additional factors involved in the control of virulence gene expression will
certainly be identiFed in the future. Although environmental signals are known to be crucial
for regulation of virulence gene expression, the mechanism for this signaling is not known,
norhavea
l
lofthefactorsinvo
lvedinenv
ironmental sensing probably been identiFed.
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