Pathogenic E. coli (page 4)
(This chapter has 4 pages)
© Kenneth Todar, PhD
Intestinal Diseases Caused by E. coli
As a pathogen, E. coli is best known for its
ability
to cause intestinal diseases. Five classes (virotypes) of E. coli
that cause diarrheal diseases are now recognized: enterotoxigenic E.
coli (ETEC), enteroinvasive E. coli (EIEC),
enterohemorrhagic
E.
coli (EHEC), enteropathogenic E. coli (EPEC), and
enteroaggregative
E.
coli (EAEC). Each class falls within a serological subgroup
and
manifests distinct features in pathogenesis.
A summary of the characteristics of diarrheagenic strains of E. coli is given in Table 2 at the
end of this article.
Enterotoxigenic E. coli (ETEC)
ETEC is an important cause of
diarrhea in infants
and travelers
in underdeveloped countries or regions of poor sanitation. In the U.S.,
it has been implicated in sporadic waterborne
outbreaks, as well as due to the consumption of soft cheeses,
Mexican-style foods and raw
vegetables. The diseases
vary from minor discomfort to a severe cholera-like syndrome. ETEC are
acquired by ingestion of contaminated food and water, and adults in
endemic
areas evidently develop immunity. The disease requires colonization and
elaboration of one or more enterotoxins. Both traits are
plasmid-encoded.
ETEC may produce a heat-labile
enterotoxin (LT) that is similar in molecular size,
sequence, antigenicity, and function to the cholera toxin (Ctx). It is
an 86kDa protein composed of an enzymatically active (A) subunit
surrounded by 5 identical binding (B) subunits. It binds to the same
identical
ganglioside receptors that are recognized by the cholera toxin (i.e.,
GM1),
and its enzymatic activity is identical to that of the cholera toxin.
ETEC may also produce a
heat stable toxin (ST) that is of low molecular size and
resistant to boiling for 30 minutes.
There are several variants of ST, of which ST1a or STp is found in E. coli isolated
from both humans and animals, while ST1b or STh is predominant in human
isolates only. The ST enterotoxins are
peptides
of molecular weight about 4,000 daltons. Their small size explains why
they are not inactivated by heat. ST causes an increase in cyclic GMP
in
host cell cytoplasm leading to the same effects as an increase in cAMP.
ST1a
is known to act by binding to a guanylate cyclase that is located on
the
apical membranes of host cells, thereby activating the enzyme. This
leads
to secretion of fluid and electrolytes resulting in diarrhea.
The
infective dose of ETEC for adults has been estimated to be at least 108
cells; but the
young, the elderly and the infirm may be susceptible to lower numbers.
ETEC adhesins are fimbriae
which are species-specific. For
example,
the K-88 fimbrial Ag is found on strains from piglets; K-99 Ag is found
on strains from calves and lambs; CFA I, and CFA II, are found on
strains
from humans. These fimbrial adhesins adhere to specific receptors on
enterocytes
of the proximal small intestine.
Symptoms ETEC infections include diarrhea
without fever. The
bacteria
colonize the GI tract by means of a fimbrial adhesin, e.g. CFA I and
CFA
II, and are noninvasive, but
produce either the LT or ST toxin.
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Enteroinvasive E. coli (EIEC)
EIEC closely resemble Shigella in their
pathogenic mechanisms
and the kind of clinical illness they produce. EIEC penetrate and
multiply
within epithelial cells of the colon causing widespread cell
destruction.
The clinical syndrome is identical to Shigella dysentery and
includes
a dysentery-like diarrhea with fever.
EIEC apparently lack fimbrial
adhesins
but do possess a specific adhesin that, as in Shigella, is
thought
to be an outer membrane protein. Also, like Shigella, EIEC
are
invasive organisms. They do
not produce LT or ST toxin.
There
are no known animal reservoirs of EIEC. Hence the primary source for
EIEC appears to be infected
humans. Although the infective dose of Shigella is low (in
the range of 10 to few
hundred cells), volunteer feeding studies showed that at least 106
EIEC organisms are
required to cause illness in healthy adults. Unlike typical E. coli,
EIEC are
non-motile, do not decarboxylate lysine and do not ferment lactose.
Pathogenicity of EIEC is primarily due to its ability to invade and
destroy colonic tissue. The
invasion phenotype, encoded by a high molecular weight plasmid, can be
detected by PCR and probes for specific for invasion genes.
Enteropathogenic E. coli (EPEC)
EPEC induce a profuse watery,
sometimes bloody, diarrhea.
They are a leading cause of
infantile diarrhea in developing countries. Outbreaks have been linked
to the
consumption of contaminated drinking water as well as some meat
products. Pathogenesis of EPEC involves a plasmid-encoded protein
referred to as EPEC adherence factor
(EAF) that enables localized
adherence of bacteria to
intestinal cells and a non fimbrial adhesin designated intimin, which is an
outer
membrane protein that mediates the final stages of adherence. They do
not produce ST or LT toxins.
Adherence of EPEC strains to the intestinal mucosa is a very
complicated
process and produces dramatic effects in the ultrastructure of the
cells
resulting in rearrangements of actin in the vicinity of adherent
bacteria.
The phenomenon is sometimes called "attachment and effacing" of
cells.
EPEC strains are said to be "moderately-invasive", meaning they
are
not as invasive as Shigella,
and unlike ETEC or EAEC, they
cause
an inflammatory response. The diarrhea and other symptoms of EPEC
infections
probably are caused by bacterial invasion of host cells and
interference
with normal cellular signal transduction, rather than by production of
toxins.
Through volunteer
feeding studies the infectious dose of EPEC in healthy adults has been
estimated to be
106 organisms.
Some types of EPEC are referred to as diffusely
adherent E. coli
(DAEC), based on specific patterns of adherence. They are an
important
cause of traveler's diarrhea in Mexico and in North Africa.
Enteroaggregative E. coli (EAEC)
The distinguishing feature of EAEC strains is
their ability to
attach to tissue culture cells in an aggregative manner. These strains
are associated with persistent diarrhea in young children. They
resemble
ETEC strains in that the bacteria adhere to the intestinal mucosa and
cause
non-bloody diarrhea without invading or causing inflammation. This
suggests
that the organisms produce an enterotoxin of some sort. Recently, a
distinctive
heat-labile plasmid-encoded toxin has been isolated from these strains,
called the EAST (EnteroAggregative ST) toxin.
They
also produce a hemolysin related to the hemolysin produced by E.
coli strains involved in urinary tract infections. The role of the
toxin and the hemolysin in virulence has not been proven. The
significance
of EAEC strains in human disease is controversial.
Enterohemorrhagic
E. coli (EHEC)
EHEC are recognized as the primary cause of hemorrhagic colitis (HC) or bloody
diarrhea, which can progress to the potentially fatal hemolytic uremic syndrome (HUS).
EHEC
are characterized by the production of verotoxin or Shiga toxins (Stx). Although Stx1
and Stx2
are most often implicated in human illness, several variants of Stx2
exist.
There are many
serotypes of Stx-producing E. coli , but only those that have
been clinically
associated with HC are designated as EHEC. Of these, O157:H7 is the prototypic EHEC and
most often implicated in illness worldwide. The infectious dose for
O157:H7 is estimated to be 10
- 100 cells; but no information is available for other EHEC serotypes.
EHEC infections are
mostly food or water borne and have implicated undercooked ground beef,
raw milk, cold sandwiches, water, unpasteurized apple juice and
vegetables
EHEC are
considered
to be "moderately invasive". Nothing is known about the
colonization
antigens of EHEC but fimbriae are presumed to be involved. The
bacteria
do not invade mucosal cells as readily as Shigella, but EHEC
strains
produce a toxin that is virtually identical to the Shiga toxin.
The toxin plays a role in the intense inflammatory response produced by
EHEC strains and may explain the ability of EHEC strains to cause HUS.
The toxin is phage encoded and its production is enhanced by iron
deficiency.
E. coli O157:H7
Transmission EM. American Society for Microbiology
Table 2. Diarrheagenic E.
coli: virulence determinants and characteristics of disease
ETEC
fimbrial adhesins e.g. CFA I, CFAII, K88. K99
non invasive
produce LT and/or ST toxin
watery diarrhea in infants and travelers; no inflammation, no fever
EIEC
nonfimbrial adhesins, possibly outer membrane protein
invasive (penetrate and multiply within epithelial cells)
does not produce shiga toxin
dysentery-like diarrhea (mucous, blood), severe inflammation, fever
EPEC
non fimbrial adhesin (intimin)
EPEC adherence factor (EAF)
enables localized adherence of bacteria to
intestinal cells
moderately invasive (not as invasive as Shigella or EIEC)
does not produce LT or ST; some reports of shiga-like toxin
usually infantile diarrhea; watery diarrhea with blood, some
inflammation,
no fever; symptoms probably result mainly from invasion rather than
toxigenesis
EAEC
adhesins not characterized
non invasive
produce ST-like toxin (EAST) and a hemolysin
persistent diarrhea in young children without inflammation or fever
EHEC
adhesins not characterized, probably fimbriae
moderately invasive
does not produce LT or ST but does produce shiga toxin
pediatric diarrhea, copious bloody discharge (hemorrhagic colitis),
intense inflammatory response, may be complicated by hemolytic uremia
END OF CHAPTER
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