Download Pathogenesis of E. coli

asst.prof.Dr.maysa salih
Enterobacteriaceae
Small Gram-negative non-spore forming enteric bacilli
All Enterobacteriaciae:
1. ferment glucose with acid production
2. reduce nitrates (NO3 to NO2 or all the way to N2)
3. are oxidase negative
All are aerobic but can be facultatively anaerobic
Motile via peritrichous flagella except Shigella and Klebsiella which
are non-motile
Capsule, slime layer, or neither
Possess fimbriae (pili)
Complex cell wall
Antigenic Structure: plays an important role for some species in
epidemiology and classification
K (capsular) antigens: capsular polysaccharide, particularly heavy
in Klebsiella
H (flagellar) antigens: flagellar proteins of motile genera and
species; used for typing; absent in non-motile genera
(Shigella and Klebsiella)
O (somatic) antigens: O-specific polysaccharide side chain
of lipopolysaccharide; used for typing
Biochemically and metabolically diverse; ferment glucose by the
mixed acid pathway; Klebsiella, Enterobacter and Serratia utilize
the butanediol pathway
Introduction
E. coli and related bacteria constitute about 0.1% of gut flora and fecal–
oral transmission is the major route through which pathogenic strains of
the bacterium cause disease. Cells are able to survive outside the body for
a limited amount of time, which makes them ideal indicator organisms to
test environmental samples for fecal contamination. The bacterium can
also be grown easily and inexpensively in a laboratory setting, E. coli is
the most widely studied prokaryotic model organism, and an important
species in the fields of biotechnology and microbiology
Pathogenic E.coli strains can be categorised based on elements that can
elicit an immune response in animals, namely:
1. O antigen: part of lipopolysaccharide layer
2. K antigen: capsule
3. H antigen: flagellin
Pathogenesis of E. coli
Over 700 antigenic types (serotypes) of E. coli are recognized based
on O, H, and K antigens. At one time serotyping was important in
distinguishing the small number of strains that actually cause disease.
Thus, the serotype O157:H7 (O refers to somatic antigen; H refers to
flagellar antigen) is uniquely responsible for causing HUS (hemolytic
uremic syndrome). Nowadays, particularly for diarrheagenic strains
(those that cause diarrhea) pathogenic E. coli are classified based on their
unique virulence factors and can only be identified by these traits. Hence,
analysis for pathogenic E. coli usually requires that the isolates first be
identified as E. coli before testing for virulence markers.
Pathogenic strains of E. coli are responsible for three types of infections
in humans: urinary tract infections (UTI), neonatal meningitis,
and intestinal diseases (gastroenteritis). The diseases caused (or not
caused) by a particular strain of E. coli depend on distribution and
expression of an array of virulence determinants, including adhesins,
invasins, toxins, and abilities to withstand host defenses. These are
summarized in Table 1 and applied to the discussion of pathogenic
strains E. coli below.
Pathophysiology
Acute bacterial meningitis
The vast majority of neonatal meningitis cases are caused by E
coli and group B streptococcal infections (28.5% and 34.1% overall,
respectively). Pregnant women are at a higher risk of colonization with
the K1 capsular antigen strain of E coli. This strain is also commonly
observed in neonatal sepsis, which carries a mortality rate of 8%; most
survivors have subsequent neurologic or developmental abnormalities.
Low birth weight and a positive cerebrospinal fluid (CSF) culture result
portend a poor outcome. In adults, E coli meningitis is rare but may occur
following neurosurgical trauma .
Pneumonia
E coli respiratory tract infections are uncommon and are almost always
associated with E coli UTI. No virulence factors have been implicated. E
coli pneumonia may also result from micro aspiration of upper airway
secretions that have been previously colonized with this organism in
severely ill patients; hence, it is a cause of nosocomial pneumonia.
However, E coli pneumonia may also be community-acquired in patients
who have underlying disease such as diabetes mellitus,
alcoholism, chronic obstructive pulmonary disease, and E coli UTI. E coli
pneumonia usually manifests as a bronchopneumonia of the lower lobes
and may be complicated by empyema. E coli bacteremia precedes
pneumonia and is usually due to another focus of E coli infection in the
urinary or GI tract.
Intra-abdominal infections
E coli intra-abdominal infections often result from a perforated viscus
(eg, appendix, diverticulum) or may be associated with intra-abdominal
abscess, cholecystitis, and ascending cholangitis. Patients with diabetes
mellitus are also at high risk of developing pylephlebitis of the portal vein
and liver abscesses.Escherichia coli liver abscess
Intra-abdominal abscesses are usually polymicrobial and can be caused
by spontaneous or traumatic GI tract perforation or after anastomotic
disruption with spillage of colon contents and subsequent peritonitis.
They can be observed in the postoperative period after anastomotic
disruption. Abscesses are often polymicrobial, and E coli is one of the
more common gram-negative bacilli observed together with anaerobes.
Cholecystitis and cholangitis result from obstruction of the biliary system
from biliary stone or sludge, leading to stagnation and bacterial growth
from the papilla or portal circulation. When bile flow is obstructed,
colonic organisms, including E coli, colonize the jejunum and duodenum.
Interestingly, partial obstruction is more likely than complete obstruction
to result in infection, bacteremia, bactibilia, and gallstones.
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.
1-Enterotoxigenic E. coli (ETEC)
ETEC is an important cause of diarrhea in infants and travelers in underdeveloped
countries or regions of poor sanitation. 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. ST causes an increase in cyclic GMP in host cell
cytoplasm leading to the same effects as an increase in cAMP. This leads to secretion
of
fluid
and
electrolytes
resulting
in
diarrhea.
ETEC adhesins are fimbriae which are species-specific; 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.
2-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.
3-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 "moderatelyinvasive", 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.
4-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.
5-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 orShiga toxins (Stx).
Although Stx1 and Stx2 are most often implicated in human illness, several variants
of Stx2 exist.
Urinary tract infections
The urinary tract is the most common site of E coli infection, and more
than 90% of all uncomplicated UTIs are caused by E coli infection. The
recurrence rate after a first E coli infection is 44% over 12 months. E
coli UTIs are caused by uropathogenic strains of E coli. E coli causes a
wide range of UTIs, including uncomplicated urethritis/cystitis,
symptomatic cystitis, pyelonephritis, acute prostatitis, prostatic abscess,
and urosepsis. Uncomplicated cystitis occurs primarily in females who
are sexually active and are colonized by a uropathogenic strain of E coli.
Subsequently, the periurethral region is colonized from contamination of
the colon, and the organism reaches the bladder during sexual intercourse.
Uropathogenic strains of E coli have an adherence factor called P
fimbriae, or pili. These P fimbriae mediate the attachment of E coli to
uroepithelial cells. Thus, patients with intestinal carriage of E coli that
contains P fimbriae are at greater risk of developing UTI than the general
population. Complicated UTI and pyelonephritis are observed in elderly
patients with structural abnormalities or obstruction such as prostatic
hypertrophy or neurogenic bladders or in patients with urinary catheters.
Factors of E. coli involved in urinary tract virulence
Virulence factor
Localisation Function
Type 1 fimbriae
P fimbriae
Bacterial
surface
Adhesion to mucosal epithelium and
tissue
matrix,
invasion,
biofilm
formation
Bacterial surface
Adhesion to mucosal epithelium and
tissue matrix, cytokine induction
S fimbriae
Bacterial surface
Adhesion to mucosal and endothelial
cells, and to tissue matrix
F1C fimbriae
Bacterial surface
Adhesion to mucosal and endothelial
cells
Thin
aggregative
Bacterial surface
fimbriae (curli)
Adhesion to mucosal cells and matrix,
biofilm formation
Flagellum
Bacterial surface
Motility, adaptation, fitness
Bacterial surface
Antiphagocytic, anticomplement effect,
serum resistance, evasion of immunerecognition
Lipopolysaccharide
Bacterial surface
Endotoxic effects, ‘O’-antigen, cytokine
induction, serum resistance, immunoadjuvant
Outer
proteins
Bacterial surface
Receptor and transport function
α-Haemolysin
Exported
Cytotoxicity, haemolysis
Cytotoxic
factor 1
Exported
Interference
apoptosis
Secreted
autotransporter toxin
Exported
Cytotoxicity
Cytolethal
toxin
Exported
Cytotoxicity
Cytolysin A
Exported
Cytotoxicity
Enterobactin
Exported
Growth under iron restriction
Aerobactin
Exported
Growth under iron restriction
Yersiniabactin
Exported
Growth under iron restriction
Capsule
membrane
necrotising
distending
Laboratory diagnosis
with
phagocytosis
and
microscopy will show gram-negative rods, with no particular cell
arrangement. Then, either MacConkey agar or EMB agar (or both) are
inoculated. On MacConkey agar, deep red colonies are produced, as the
organism is lactose-positive, and fermentation of this sugar will cause the
medium's pH to drop, leading to darkening of the medium. Growth on
EMB agar produces black colonies with a greenish-black metallic sheen.
This is diagnostic of E. coli. The organism is also lysine positive, and
grows on TSI slant with a (A/A/g+/H2S-) profile. Also, IMViC is {+ + – } for E. coli; as it is indole-positive (red ring) and methyl red-positive
(bright red), but VP-negative (no change-colourless) and citrate-negative
(no change-green colour). Tests for toxin production can use mammalian
cells in tissue culture, which are rapidly killed by shiga toxin. Although
sensitive and very specific
Treatment
Bacterial infections are usually treated with antibiotics. However, the
antibiotic sensitivities of different strains of E. coli vary widely. As gramnegative organisms, E. coli are resistant to many antibiotics that are
effective against gram-positive organisms. Antibiotics which may be used
to treat E. coli infection include amoxicillin, as well as other
semisynthetic penicillins,
many cephalosporins, carbapenems, aztreonam, trimethoprimsulfamethoxazole, ciprofloxacin, nitrofurantoin and the aminoglycosides.