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

1284 Chapter 23: Pathogens and Infection
ESCAPE
endosome or
phagosome
1
intracellular pathogen
2
PREVENT FUSION
WITH LYSOSOMES
3
SURVIVE IN
PHAGOLYSOSOME
host cell
fusion with
lysosomes to form
phagolysosome
Figure 23–22 Choices that an
intracellular pathogen faces. After
entry into a host cell, generally through
phagocytosis into a membrane-enclosed
compartment, intracellular pathogens can
use one of three strategies to survive and
replicate. Pathogens that follow strategy
(1) include all viruses, Trypanosoma cruzi,
Listeria monocytogenes, and Shigella
flexneri. Those that follow strategy (2)
include Mycobacterium tuberculosis and
Legionella pneumophila. Those that follow
strategy (3) include Salmonella enterica,
Coxiella burnetii, and Leishmania.
Some Intracellular Pathogens Escape from the Phagosome into
the Cytosol
The intracellular parasites just discussed raise a general problem that faces all
MBoC6 m24.30/23.22
intracellular pathogens, including viruses, bacteria, and eukaryotic parasites:
they must find a cell compartment in which they can replicate. After their endocytosis
by a host cell, they usually find themselves in an endosomal compartment,
which normally would fuse with lysosomes to form a phagolysosome—a dangerous
place for pathogens. To survive, pathogens use a variety of strategies. Some
escape from the endosomal compartment before such fusion. Others remain in
the endosomal compartments but modify it so that it no longer fuses with lysosomes.
Still others have evolved to weather the harsh conditions in the phagolysosome
(Figure 23–22).
Trypanosoma cruzi uses the escape route by secreting a pore-forming toxin
that lyses the lysosome membrane, releasing the parasite into the host cell’s cytosol
(see Figure 23–21). The bacterium Listeria monocytogenes uses a similar strategy.
Following phagocytosis by the zipper mechanism, it secretes a protein called
listeriolysin O, which disrupts the phagosomal membrane, releasing the bacteria
into the cytosol (Figure 23–23).
Many Pathogens Alter Membrane Traffic in the Host Cell to Survive
and Replicate
The survival and reproduction of many intracellular pathogens requires that they
modify membrane (vesicular) traffic in the host cell. They may, for example, prevent
the normal fusing of endosomes with lysosomes, or adapt themselves to
1 Listeria attaches
to E-cadherin
epithelial host cell
E-cadherin
2
uptake by
zipper mechanism
4 listeriolysin-mediated
membrane disruption
6 secreted listeriolysin now
destroyed in host proteasomes
phagosome
3 listeriolysin
secretion
5 bacterial release
and replication
pH <6.0 pH >6.0
proteasome
Figure 23–23 Escape of Listeria monocytogenes by selective destruction of the phagosomal membrane. The bacterium
attaches to E-cadherin on the surface of host epithelial cells and induces its own uptake by the zipper mechanism (see
Figure 23–19A). Within the phagosome, the bacterium secretes the protein listeriolysin O, which is activated at pH <6 and
forms oligomers in the phagosome membrane, thereby creating large pores and eventually disrupting the membrane. Once
in the host-cell cytosol, the bacteria begin to replicate and continue to secrete listeriolysin O; because the pH in the cytosol
is >6, however, the listeriolysin O there is inactive and is also rapidly degraded by proteasomes. Thus, the host cell’s plasma
membrane remains intact.