Anthrax (Bacillus anthracis), Molecular Biology of
309
caused by a specifc bacterium. He later developed the frst live attenuated bacterial
vaccine with a heat-attenuated strain oF
B. anthracis.
Despite its illustrious beginnings
as a subject oF research, an understanding oF the molecular biology oF
B. anthracis
has lagged behind that oF some other bacteria.
Bacillus anthracis
has recently come
back into Focus as a target oF research with the goal oF being able to readily detect
this bacterium in environmental samples and to understand its pathogenesis and
evolution better.
1
Anthrax
Bacillus anthracis
is a gram-positive, spore-
Forming bacterium that normally resides
in the soil, but when taken up into the
body, causes anthrax. This Facultative aer-
obe grows on many types oF culture media
and its colonies appear mucoid and are not
generally
hemolytic.
Upon
microscopic
examination, chains oF encapsulated, non-
motile, rod-shaped bacteria are seen. ±or
inFection to occur, spores oF
B. anthracis
may be taken up through one oF three
routes: inhalation, ingestion, or via an
abrasion oF the skin. ±rom there, the
spores are engulFed by macrophages and
carried to regional lymph nodes. Spore
germination in macrophages appears to be
required For the establishment oF disease,
and the spores require this intracellular
environment to stimulate germination. It
has
been shown
that,
at
least in
cul-
ture, the newly vegetative bacilli escape
the phagosome to reach the cytoplasm
oF macrophages, where they multiply and
are eventually released into the extracellu-
lar environment. Macrophages, thereFore,
end
up
playing
a
major
role
in
the
pathogenesis oF
B. anthracis
because they
provide an appropriate environment For
spore germination and they also provide
a transportation route that gives the bac-
teria access to the blood stream where
high levels oF bacteremia can ensue. Once
this stage is reached, a shock-like syn-
drome and death Follow; although this
severe disease course is usually associated
with inhalation or gastrointestinal anthrax,
a cutaneous anthrax inFection is gener-
ally contained prior to the achievement oF
bacteremia.
The majority oF
B. anthracis
strains carry
two large virulence plasmids, called pXO1
and pXO2. Both plasmids are required For
Full virulence. pXO2 carries the
cap
region,
an
operon
encoding
a
poly-D-glutamic
acid capsule that helps the bacteria evade
the immune system by allowing them to
resist phagocytosis. The other plasmid,
pXO1, carries
pagA, lef
,and
cya
,thegenes
encoding the three components oF the
anthrax
toxin:
protective
antigen
(PA),
lethal Factor (L±) and edema Factor (E±)
respectively. The symptoms oF anthrax are
largely mediated by this toxin. In Fact, an
anthrax inFection can be Fatal even aFter the
blood has been cleared oF all
B. anthracis
owing to the toxin that has already been
released into the body.
The
toxin
proteins
work
in
binary
combinations
to
produce
toxic
eFFects;
PA is the carrier molecule that delivers
the
enzymatic
portions
oF
the
toxin,
and
L±,
to
the
cytosol
oF
cells.
There, E±, an adenylate cyclase, increases
cAMP
levels,
which
are
presumed
to
play a role in the development oF the
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