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

1294 Chapter 23: Pathogens and Infection
Because the acquisition of drug resistance is almost inevitable, it is crucial that
we continue to develop innovative treatments for infectious diseases. We must
also take additional measures to delay the onset of drug resistance.
Summary
All pathogens share the ability to interact with host cells in diverse ways that promote
the replication and spread of the pathogen. Pathogens often colonize the host
by adhering to or invading the epithelial surfaces that line the respiratory, gastrointestinal,
and urinary tracts, as well as the other body surfaces in direct contact with
the environment. Intracellular pathogens, including all viruses and many bacteria
and protozoa, invade host cells by one of several mechanisms. Viruses rely largely on
receptor-mediated endocytosis, whereas bacteria exploit cell adhesion and phagocytic
pathways; in both cases, the host cell provides the machinery and energy for
the invasion. Protozoa, by contrast, employ unique invasion strategies that usually
require significant metabolic expense on the part of the invader. Once inside, intracellular
pathogens seek out a cell compartment that is favorable for their survival
and replication, frequently altering host membrane traffic and exploiting the hostcell
cytoskeleton for intracellular movement. Pathogens evolve rapidly, so that new
infectious diseases frequently emerge, and old pathogens acquire new ways to evade
our attempts at treatment, prevention, and eradication.
What we don't know
• What are the genetic and molecular
features that differ between pathogens
and members of the normal human
microbiota? How can our immune
system distinguish between the two?
• To what extent are common hostcell
biological pathways and molecules
hijacked by diverse microbes?
• Can host-cell defense molecules be
mobilized by drugs to fight infection?
Problems
Which statements are true? Explain why or why not.
23–1 Our adult bodies harbor about 10 times more
microbial cells than human cells.
23–2 The microbiomes from healthy humans are all
very similar.
23–3 Pathogens must enter host cells to cause disease.
23–4 Viruses replicate their genomes in the nucleus of
the host cell.
23–5 You should not take antibiotics for diseases caused
by viruses.
Discuss the following problems.
23–6 In order to survive and multiply, a successful
pathogen must accomplish five tasks. Name them.
23–7 Clostridium difficile infection is the leading cause
of hospital-associated gastrointestinal illness. It is typically
treated with a course of antibiotics, but the infection recurs
in about 20% of cases. C. difficile infections are difficult to
eradicate because the bacteria exist in two forms: a replicating,
toxin-producing form and a spore form that is resistant
to antibiotics. Fecal microbiota transplantation—the
transfer of normal gut microbiota from a healthy individual—can
resolve >90% of recurrent infections, a much better
cure rate than further antibiotic treatment alone. Why
do you suppose microbiota transplantation is so effective?
23–8 What are the three general mechanisms for horizontal
gene transfer?
23–9 The Gram-negative bacterium Yersinia pestis, the
causative agent of the plague, is extremely virulent. Upon
infection, Y. pestis injects a set of effector proteins into
macrophages that suppresses their phagocytic behavior
and also interferes with their innate immune responses.
One of the effector proteins, YopJ, acetylates serines and
threonines on various MAP kinases, including the MAP
kinase kinase kinase TAK1, which controls a key signaling
step in the innate immune response pathway. To determine
how YopJ interferes with TAK1, you transfect human
cells with active YopJ (YopJ WT ) or inactive YopJ (YopJ CA )
and with FLAG-tagged active TAK1 (TAK1 WT ) or inactive
TAK1 (TAK1 K63W ), and assay for total TAK1 and for phosphorylated
TAK1, using antibodies against the FLAG tag or
against phosphorylated TAK1 (Figure Q23–1). How does
YopJ block the TAK1 signaling pathway? How do you suppose
the serine/threonine acetylase activity of YopJ might
interfere with TAK1 activation?
TAK1 WT WT WT K63W
YopJ
IP: α-FLAG-TAK1
IB: α-pTAK1
IP: α-FLAG-TAK1
IB: α-FLAG-TAK1
- CA WT
1 2 3 4
kd
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Figure Q23–1 Effects of YopJ on TAK1 phosphorylation (Problem
23–9). TAK1 was immunoprecipitated (IP) using antibodies against
the FLAG tag (α-FLAG-TAK1). Total TAK1 in the immunoprecipitation
was assayed by immunoblot (IB) using the same antibody.
Phosphorylated TAK1 was assayed by IB using antibodies specific
for phospho-TAK1 (α-pTAK1). A scale of protein molecular mass is
shown at right in kilodaltons. (From N. Paquette et al., Proc. Natl
Acad. Sci. USA 109:12710–12715, 2012. With permission from
National Academy of Sciences.)
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