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

1282 Chapter 23: Pathogens and Infection
(A)
ZIPPER MECHANISM
invasin
HOST CELL
BACTERIUM
invasin receptors
(integrins, cadherins)
activated receptors
actin
polymerization
Rho
WASp
Arp 2/3
(B)
TRIGGER MECHANISM
actin
polymerization
HOST CELL
direct effect
on actin
BACTERIUM
type III secretion
apparatus
injected proteins actin
polymerization
Rho
WASp
Arp 2/3
Figure 23–19 Mechanisms used by
bacteria to induce phagocytosis by host
cells that are normally nonphagocytic.
(A) In the zipper mechanism, bacteria
express an invasion protein that binds with
high affinity to a host-cell receptor, which
is often a cell–cell or cell–matrix adhesion
protein. (B) In the trigger mechanism,
bacteria inject a set of effector molecules
into the host-cell cytosol through a type III
secretion system called SPI1 (Salmonella
pathogenicity island 1), inducing membrane
ruffling. Both the zipper and trigger
mechanisms cause the polymerization of
actin at the site of bacterial attachment
by activating Rho family small GTPases
and the Arp 2/3 complex. (C) A scanning
electron micrograph showing a very early
stage of Salmonella enterica invasion
by the trigger mechanism. Bacteria
(pseudocolored yellow) are shown
surrounded by a small membrane ruffle.
(D) Fluorescence micrograph showing that
the large ruffles that engulf the Salmonella
bacteria are actin-rich. The bacteria are
labeled in green and actin filaments in red;
because of the color overlap, the bacteria
appear yellow. (C, from Rocky Mountain
Laboratories, NIAID, NIH; D, from
J.E. Galán, Annu. Rev. Cell Dev. Biol.
17:53–86, 2001. With permission from
Annual Reviews.)
(C)
(D)
4 µm 20 µm
is similar to the ruffling induced by some extracellular growth factors, suggesting
that the bacteria exploit normal intracellular signaling pathways.
MBoC6 m24.26/23.19
Intracellular Eukaryotic Parasites Actively Invade Host Cells
The uptake of viruses and bacteria into host cells is carried out largely by the host,
with the pathogen being a relatively passive participant. In contrast, intracellular
eukaryotic parasites, which are typically much larger than other types of intracellular
pathogens, invade host cells through a variety of complex pathways that
usually require energy expenditure by the parasite.
Toxoplasma gondii,a cat parasite that also causes occasional serious human
infections, is an example. When this protozoan contacts a host cell, it protrudes
an unusual microtubule-based structure called a conoid, which facilitates entry
into the host cell (Figure 23–20). The energy for invasion seems to come from
actin polymerization in the parasite rather than host cytoskeleton, and invasion
also requires at least one unusual parasite myosin motor protein (Class XIV; see
Figure 16–40). At the point of contact, the parasite discharges effector proteins
from secretory organelles into the host cell, and these proteins target various host
pathways to enable invasion, to block an innate immune response, and promote
survival. As the parasite moves into the host cell, a membrane derived from the
host-cell plasma membrane surrounds it. Remarkably, the parasite removes host
transmembrane proteins from the surrounding membrane as it forms, so that
the parasite is protected in a membrane-enclosed compartment that does not
fuse with lysosomes and does not participate in host-cell membrane trafficking
processes (see Figure 23–20). The specialized membrane is selectively porous: it
allows the parasite to take up small metabolic intermediates and nutrients from
the host cell’s cytosol but excludes macromolecules. Malaria parasites invade
human red blood cells using a similar mechanism.