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

CELL BIOLOGY OF INFECTION
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adaptor
proteins
glycolipid
adhesin
kidney
epithelial
cell
pilus
(A)
5 µm
(B)
1 µm
(C)
bacterium
these organs are periodically flushed by urination and by peristalsis, respectively,
which washes away most microbes.
Pathogenic bacteria and eukaryotic parasites that infect these epithelial surfaces
have evolved specific mechanisms for overcoming these protective mechanisms.
Those that infect the urinary tract, for example, adhere tightly to the
epithelial lining via specific adhesins, which are proteins or protein complexes
that recognize and bind to cell-surface molecules on the epithelium. An important
group of adhesins in E. coli strains that infect the kidney are components of
the pili—surface projections that can be several micrometers long and thus able
to span the thickness of the protective mucus layer; at the tip of each pilus is an
adhesin protein that binds tightly to the D-galactose–D-galactose disaccharide
on glycolipids on the surface of kidney cells (Figure 23–15). Strains of E. coli that
infect the bladder rather than the kidney express a second kind of pilus with a different
adhesin protein that binds to bladder epithelial cells. It is the specificity of
the adhesin proteins on the tips of the two types of MBoC6 pili that m24.21/23.15 is responsible for the
bacteria’s colonizing of the different parts of the urinary tract.
The stomach is an especially hostile environment for pathogens. Besides the
thick layer of mucus and peristaltic washing, it is filled with acid (average pH ≈2),
which is lethal to almost all bacteria ingested in food. Yet, it is home to a microbiota
of hundreds of resident species, including the bacterium H. pylori, which,
as we discussed earlier, is the major cause of stomach ulcers and some stomach
cancers. The hypothesis that a persistent bacterial infection could cause stomach
ulcers was initially met with skepticism. The young Australian doctor who made
the initial discovery finally proved the point: he drank a pure culture of H. pylori
and developed inflammation of the stomach, which often precedes the development
of ulcers. A short course of antibiotics can now effectively cure a patient
of recurrent stomach ulcers. Remarkably, H. pylori is able to persist for life as a
commensal in most humans. One way in which it survives in the stomach is by
producing the enzyme urease, which converts urea to ammonia that neutralizes
the acid in its immediate vicinity. The bacterium also uses its flagellum for chemotactic
motility, allowing it to seek out the more neutral pH near the surface
of gastric epithelial cells. H. pylori virulence proteins that target both epithelial
and immune cells help H. pylori persist in the stomach, but they can also induce
chronic inflammation, alteration in host gene expression, changes in cell proliferation
and apoptosis, and disruption of cell–cell junctions, all of which are predisposing
factors for stomach cancer.
Figure 23–15 Pathogenic E. coli in
the infected bladder of a mouse.
(A) Scanning electron micrograph of
uropathogenic E. coli, a common cause of
bladder and kidney infections. The bacteria
are attached to the surface of epithelial
cells lining the infected bladder. (B) A closeup
view of one of the bacteria showing
the pili on its surface. (C) An E. coli pilus
has adaptor proteins on its tip that bind to
glycolipids on the surface of kidney cells.
(A, from G.E. Soto and S.J. Hultgren,
J. Bacteriol. 181:1059–1071, 1999. With
permission from the American Society for
Microbiology; B, courtesy of D.G. Thanassi
and S.J. Hultgren, Methods 20:111–126,
2000. With permission from Academic
Press.)
Extracellular Pathogens Disturb Host Cells Without Entering Them
Extracellular pathogens can cause serious disease without entering host cells.
Bordetella pertussis, the bacterium that causes whooping cough, for example, colonizes
the respiratory epithelium and circumvents the normal mechanism that