Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1270 Chapter 23: Pathogens and Infection
bacterial pathogens, virulence genes often encode secreted toxic proteins (toxins)
that interact with host cell structural or signaling proteins to elicit a response
that is beneficial to the pathogen. Several of these bacterial toxins are among the
most potent of known human poisons. Bacterial toxins are often composed of two
protein components—an A subunit with enzymatic activity, and a B subunit that
binds to specific receptors on the host cell surface and directs the trafficking of
the A subunit to the cytosol by various routes (Figure 23–6). The Vibrio cholerae
phage, for example, encodes the two subunits of cholera toxin (Movie 23.2). The
A subunit catalyzes the transfer of an ADP-ribose moiety from NAD + to the trimeric
G protein G s (see Figure 15–23), which activates adenylyl cyclase to make
cyclic AMP (see Figure 15–25). ADP-ribosylation prevents inactivation of the G
protein and results in the overaccumulation of intracellular cyclic AMP and the
release of ions and water into the intestinal lumen, leading to the watery diarrhea
associated with cholera. The infection then spreads to new hosts via released bacteria,
which can contaminate food and water.
Some pathogenic bacteria secrete multiple toxins, each of which targets a different
signaling pathway in host cells. Anthrax, for example, is an acute infectious
disease of sheep, cattle, and occasionally humans. It is caused by contact with
spores of the Gram-positive bacterium Bacillus anthracis. Dormant spores can
survive in soil for long periods. If inhaled, ingested, or rubbed into breaks in the
skin, spores can germinate and the bacteria replicate. The bacteria secrete two
toxins with identical B subunits but different A subunits. The B subunits bind to
a host cell-surface receptor protein to transfer the two different A subunits into
anthrax toxin
cholera or
pertussis toxin
B subunit
A subunit
HOST-CELL
CYTOSOL
toxin receptor
endosome
lethal factor
cleaves MAPKK members
drop in blood pressure
endosome
Golgi
ER
A subunit in cytosol
edema factor cholera toxin
raises cAMP levels raises cAMP levels
edema
diarrhea
pertussis toxin
raises cAMP levels
inhibits immunity
Figure 23–6 Bacterial toxin entry into
host cells. Bacterial toxins are often
composed of A and B protein subunits.
The B (binding) subunit of the toxin
interacts with host-cell toxin receptors,
enabling endocytosis and intracellular
trafficking of B subunit as well as its
associated and enzymatically active
A subunit(s). In the case of Bacillus
anthracis, the B subunit changes
conformation in the low pH environment
of the endosome to form a pore through
which two different A subunits, lethal
factor and edema factor, are transported
across the membrane of the endosome
in an unfolded conformation. In the
cases of Vibrio cholerae toxin and
Bordetella pertussis toxin, the B and A
subunits are transported to the Golgi
apparatus and then to the endoplasmic
reticulum (ER), where the A subunits are
then translocated into the cytosol in an
unfolded conformation through a proteintranslocation
channel.