Page 54 - Review of Medical Microbiology and Immunology ( PDFDrive )

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CHAPTER 7 Pathogenesis
their signal transduction function. Glucosylation by exo-
stimulating the enteric nervous system, which activates the
toxin B causes disaggregation of actin filaments in the
vomiting center in the brain.
cytoskeleton, leading to apoptosis and cell death.
(9) Exfoliatin is a protease produced by S. aureus that
(5) Multiple toxins are produced by Clostridium perfrin-
causes scalded skin syndrome. Exfoliatin cleaves desmo-
gens and other species of clostridia that cause gas gangrene.
A total of 7 lethal factors and 5 enzymes have been charac-
terized, but no species of Clostridium makes all 12 prod-
the detachment of the superficial layers of the skin. Exfolia-
tin is also called epidermolytic toxin.
ucts. The best characterized is the alpha toxin, which is a
(10) Panton-Valentine (PV) leukocidin is a pore-form-
lecithinase that hydrolyzes lecithin in the cell membrane, glein, a protein in the desmosomes of the skin, resulting in
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ing exotoxin produced by methicillin-resistant strains of
resulting in destruction of the membrane and widespread
cell death. The other four enzymes are collagenase, prote-
S. aureus (MRSA). It destroys white blood cells, skin, and
subcutaneous tissue. The two subunits of the toxin assem-
ase, hyaluronidase, and deoxyribonuclease (DNase). The
seven lethal toxins are a heterogeneous group with hemo-
lytic and necrotizing activity. Certain strains of C. perfrin-
contents exit into the extracellular space.
(11) Erythrogenic toxin, produced by S. pyogenes,
gens produce an enterotoxin that causes watery diarrhea
This enterotoxin acts as a superantigen similar to the
causes the rash characteristic of scarlet fever. Its mecha-
enterotoxin of S. aureus (see point 8).
nism of action is similar to that of TSST (i.e., it acts as a
(6) Three exotoxins are produced by Bacillus anthracis,
superantigen; see point 8 earlier). The DNA that codes for
the agent of anthrax: edema factor, lethal factor, and protec-
tive antigen. The three exotoxins associate with each other,
genic bacteria do not cause scarlet fever, although they can
but each component has a distinct function. Edema factor
cause pharyngitis.
is an adenylate cyclase that raises the cyclic AMP concen- the toxin resides on a temperate bacteriophage. Nonlyso-
tration within the cell, resulting in loss of chloride ions and
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Gram-Negative Bacteria
water and consequent edema formation in the tissue
The exotoxins produced by gram-negative bacteria also
(Table 7–12). Lethal factor is a protease that cleaves a phos-
phokinase required for the signal transduction pathway
different clinical effects. Two very important exotoxins are
that controls cell growth. Loss of the phosphokinase results
the enterotoxins of E. coli and V. cholerae (cholera toxin),
in the failure of cell growth and consequent cell death. Pro-
which induce an increase in the amount of cyclic AMP
tective antigen binds to a cell surface receptor and forms
within the enterocyte, resulting in watery diarrhea
pores in the human cell membrane that allow edema factor
(Table 7–12). The mechanisms of action and the clinical
and lethal factor to enter the cell. The name protective anti-
effects of exotoxins produced by gram-negative bacteria are
gen is based on the finding that antibody against this pro-
tein protects against disease. The antibody blocks the
binding of protective antigen, thereby preventing edema
(1) The heat-labile enterotoxin produced by E. coli
factor and lethal factor from entering the cell.
causes watery, nonbloody diarrhea by stimulating adenyl-
(7) TSST is a superantigen produced primarily by described next.
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ate cyclase activity in cells in the small intestine (Figure 7–3).
certain strains of S. aureus but also by certain strains of
The resulting increase in the concentration of cyclic AMP
S. pyogenes. TSST binds directly to class II major histocom-
causes excretion of the chloride ion, inhibition of sodium
patibility (MHC) proteins on the surface of antigen-
presenting cells (macrophages) without intracellular
into the lumen of the gut. The heat-labile toxin, which is
processing. This complex interacts with the β-chain of the
inactivated at 65°C for 30 minutes, is composed of two
T-cell receptor of many helper T cells (see the discussion of
subunits: a B subunit, which binds to a ganglioside receptor
superantigens in Chapter 58). This causes the release of
in the cell membrane, and an A subunit, which enters the
large amounts of interleukins, especially interleukin-1,
cell and mediates the transfer of ADP-ribose from NAD to
interleukin-2, and tumor necrosis factor (TNF). These
cytokines produce many of the signs and symptoms of toxic
s
G protein in the “on” position, thereby continually stimu-
shock. TSST is also a T-cell “mitogen” (i.e., it induces T cells
s
lating adenylate cyclase to synthesize cyclic AMP. This
to multiply), which contributes to the overproduction of
activates cyclic AMP–dependent protein kinase, an enzyme
cytokines. a stimulatory coupling protein (G protein). This locks the
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that phosphorylates ion transporters in the cell membrane,
(8) Staphylococcal enterotoxin is also a superantigen,
resulting in the loss of water and ions from the cell. The
but because it is ingested, it acts locally on the lymphoid
genes for the heat-labile toxin and for the heat-stable toxin
cells lining the small intestine. The enterotoxin is produced
by S. aureus in the contaminated food and causes food
In addition to the labile toxin, there is a heat-stable
poisoning, usually within 1 to 6 hours after ingestion. The
toxin, which is a polypeptide that is not inactivated by boil-
main symptoms are vomiting and watery diarrhea. The
ing for 30 minutes. The heat-stable toxin affects cyclic
prominent vomiting seen in food poisoning is thought to
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