Anthrax (Bacillus anthracis), Molecular Biology of
323
plcR
regulon in
B. anthracis
because it puts
the bacteria at a selective disadvantage due
to its effect on sporulation.
5
Regulation of Sporulation/Germination
Appropriate sporulation and germination
responses are crucial for the survival of
B. anthracis
. Spores can survive for years
and can withstand harsh environmental
conditions. The spores must be able to
sense and respond to the environment,
such that germination occurs under the
appropriate
conditions.
In
the
case
of
B. anthracis
,sporesmus
tgerm
ina
teonce
they are taken up by a host so that the
bacteria can replicate and the disease can
be established. A tricistronic operon on
pXO1 is responsible for spore germina-
tion. The genes in this operon,
gerXB,
gerXA
,a
n
d
gerXC
, are located between
pagA
and
atxA
on the plasmid. The
ger
genes have signiFcant similarity to the ger-
mination genes found in other bacilli, such
as the
gerB
operon of
B. subtilis
and the
gerI
operon of
B. cereus
. In culture, expression
of this operon is barely detectable during
exponential growth and increases rapidly
during stationary phase so that maximal
expression is seen 3 h after the initiation
of sporulation. Expression is limited to
the developing forespore. In macrophages,
spores of a
gerX
null mutant do not germi-
nate as readily as do wild-type spores, and
this is also true in mice infected subcuta-
neously with the
gerX
null strain. In the
animals, there is a signiFcant delay in the
onset of germination with the
gerX
mu-
tant, and this is associated with a Fvefold
decrease in virulence. Once the gerX null
spores have germinated, they are able to
multiply and invade the host. It has been
speculated that the rate of germination
may affect the rate of the infection and
that this may play a role in the reduced
virulence of this strain.
The
gerX
operon is not the only reg-
ulator
of
sporulation
and
germination
in
B. anthracis
;
plasmidless
strains
of
B. anthracis
germinate and grow in an-
imal models. Inosine and
L-alanine
are
two of the major germinants that induce
plasmidless strains to germinate. At physi-
ological levels, these germinants work only
in combination with other compounds.
±or alanine, an aromatic amino acid (either
L-histidine,
L-tyrosine, or
L-tryptophan) is
also required for germination, and this
has been termed the
aromatic-enhanced
alanine
response (AEA). ±or inosine, ei-
ther a nonaromatic amino acid or an
aromatic amino acid are required as coger-
minants, and these exhibit different germi-
nation kinetics. These responses have been
called AAID for amino acid – and inosine-
dependent responses. A
gerX
homolog was
found on the chromosome of
B. anthracis
and called
gerS
. Characterization of a
gerS
mutant indicated that it is involved in
both the AAID and AEA germination re-
sponses. Analogous to the situation in even
more well-characterized germination path-
ways in other bacilli, it has been proposed
that
gerS
encodes an aromatic respon-
sive element that works in conjunction
with other sensors to detect germinants
with multiple components. Homologs of
gerI
and
gerL
from the
B. cereus
germi-
nation operon have been identiFed in the
B. anthracis
genome, and they may be com-
ponents of this pathway.
6
Conclusions
Great strides have been made recently
in the development of methods for the
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