322
Anthrax (Bacillus anthracis), Molecular Biology of
regulated by
spo0A
. In conjunction with
these fndings, the pattern oF toxin gene
expression
is
aFFected
by
abrB
.I
na
parent strain, toxin expression increases
gradually throughout log phase, reaching
a
maximum
in
late
log
phase.
The
derivative
abrB
mutant strain, on the other
hand, shows a sharp increase in toxin
gene expression in early log phase, and
maximum expression is reached in mid-
log phase beFore a decline in expression is
seen in late log phase. Although it has not
yet been tested, it is likely that signaling
pathways containing AbrB play a role in
environmental sensing in
B. anthracis,
as
they do in
B. subtilis
.
4.4
AcpA
Another
major
virulence
regulator
in
B. anthracis
is AcpA, a protein with signiF-
icant similarity to AtxA. AcpA is encoded
byageneonpXO2andisaregu
la
toro
F
capsule production that works at a tran-
scriptional level. Northern blots indicate
that the genes For capsule production,
capA
to
capD
, are transcribed as one message
and thus constitute an operon. Strains
with mutations in
acpA
are signifcantly
reduced in capsule production and in viru-
lence. AcpA is involved in the bicarbonate-
mediated regulation oF capsule production.
Unlike AtxA, whose production requires a
temperature oF 37
C,
acpA
transcription
is regulated by bicarbonate.
Green et al. reported that the require-
ment For CO
2
in capsule production in-
creases in the absence oF pXO1. And, as
mentioned above, the presence oF pXO1
increases capsule synthesis in an AtxA-
dependent manner. This led Uchida et al.
to speculate that AtxA may work with
AcpA to induce capsule production. In-
deed, they Found that an
acpA
-null mutant
is complemented, not only by
acpA
but
also by
atxA
in a CO
2
-dependent Fash-
ion. This regulation is at the level oF
transcription, and the same sequences up-
stream oF
cap
are required For both AtxA-
and AcpA-mediated activation oF transcrip-
tion. Reciprocal experiments suggest that
AcpA cannot complement an
atxA
deFec-
tive strain. No obvious similarities between
the sequences upstream oF
pagA
and
cap
have been identifed, so an AtxA target
sequence is yet to be identifed.
4.5
Other Potential Virulence Factors
Homologs oF virulence genes From closely
related species have been identifed in
B. anthracis
, but their roles in virulence
have not been Fully studied. These in-
clude extracellular proteases, hemolysins,
enterotoxins,
and
phospholipases.
In
B. cereus
and
B. thuringiensis
, the expres-
sion oF some oF these nonspecifc vir-
ulence Factors is regulated by
PlcR, a
pleiotropic activator. Strains oF
B. cereus
and
B. thuringiensis
with
plcR
deletions
have
attenuated
virulence
in
a
mouse
model, indicating that the proteins turned
on by this regulator do, in Fact, play a role in
virulence. In contrast, wild-type, Fully viru-
lent
B. anthracis
has a nonsense mutation
in
plcR
and encodes a truncated, nonFunc-
tional protein. This mutation silences a
regulon; iF a Functional
plcR
is expressed
in
B. anthracis
, a number oF genes are ac-
tivated. The addition oF a Functional
plcR
does not, however, aFFect the virulence oF
the organism, but it does inhibit sporula-
tion oF
B. anthracis
in an
atxA
-dependent
manner. A strain that carries a Functional
plcR
but no Functional
atxA
sporulates nor-
mally. It has been postulated, thereFore,
that, aFter the acquisition oF pXO1, there
may have been counterselection For the
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