Enterobacteriaceae as Causes of Diarrhea: E.

coli Pathogenesis of EPEC

 EPEC attaches to small bowel through the bundle -
General Characteristics forming pilus (BFP)
 May or may not be pathogenic o Form localized adhesions (LA)
 Motile with peritrichous flagella  Intimate attachment is mediated by the interaction
 Indole (+) between intimin and the translocated intimin receptor
 Ferments sugars with acid production and gas on (Tir)
glucose formation  Tir is phosphorylated
o Binds to adaptor protein
Virulence Factors o Mediate actin rearrangements and pedestal
 Pathogenic strains produce virulence factors formation
 Found on: Plasmids
o DNA molecule that is separate form
o Can replicate independently of the
chromosomal DNA
o Bacteriophages
 Viruses that infect bacteria
 Include:
o Fimbriae
 Allow bacteria to stack up on each
other to shelter themselves from
immune systems
 Secretions systems
 The process of toxin release
 Toxins

Virulence Factors: Enterotoxin

 Movement of water and ions from tissue to vowel
resulting in watery diarrhea
 Two types of Enterotoxin
o Heat – Stable (ST)
 Activate cGMP
o Heat – Labile (LT)
 Activate Camp
 Shiga toxin
o Inhibit protein synthesis:
 Enterohemorrhagic strains of E. coli
(EHEC)
 Cytotoxic, enterotoxic, neurotoxic
 Diarrhea, ulceration of GIT
 Enteroaggregative toxin
o Produced by E. coli (EAEC)
o Causes watery diarrhea

EHEC VIRULENCE FACTORS

Factor Localization Mechanism Area of Activity
Shiga - like Toxin (stx) Prophage Cytotoxicity Endothelial cells
Initimins (eae) Pathogenicity Island Instestinal
Adhesion
Type III secretory system (LEE) epithelium
Disruption of
Serine protease Plasmid Factor V
hemocoagulation
EHEC - Hemolysin Plasmid Hemolysis RBC

Enterotoxigenic E. coli (ETEC)

 Major causal agent of Traveler’s diarrhea
 These strains express
o Heat – labile (LT – 1) enterotoxins
 An A – B toxin
 Subunit A causes intense and
prolonged hyper-secretion of chloride
ions and inhibit reabsorption of
sodium and chloride
 Gut lumen is distended with fluid
 Hypermotility and secretory diarrhea
occur, lasts for several days
 Stimulates the production of
neutralizing antibodies and cross
reacts with cholera toxin
(V. cholerae enteroxin)
 o Heat – stable (Sta) enterotoxin
 Stimulates fluid secretion EAEC Known Virulence Factors
 Poorly immunogenic
AAF Aggregative adherence fimbriae
 Short onset
o Colonization Factors (CFAs) EAST - 1 EAEC heat - stable toxin (similar to ETEC Sta)
 Facilitate attachment of E. coli strains to Pet Plasmid - encoded enterotoxin (mucus release)
intestinal epithelium role in intestinal colonisation - various activities
 Usually pili in nature Pic
(mucinase, serum resistance, haemagglutinin

Enteroinvasive E. coli (EIEC)

 Its produced disease is indistinguishable from the
dysentery produced by members of genus Shigella
o Shigella seem to be more virulent
o Fewer are required than EIEC to cause diarrhea
 Key virulence factor
o Ability to invade epithelium
 Pathogenesis
o Invades the epithelium from intestinal lumen
through M – cells
o After reaching the ET, they invade epithelial
cells and are phagocytosed by resident
macrophages
o Escapes the phagosomes of both cells Clinical Features
 While EIEC replicate within epithelial Organism Diarrhaea Fever Others
Traveller's diarrhea
cells, they induce apoptosis ETEC Severe cholera - like -
Diarrhea in infants
o Bacteria are released and can invade the
EPEC Watery - positive inflammatory response
epithelial cells from the basolateral side, move EIEC Dysentery - like + widespread cell destruction
into cytoplasm by triggering actin EHEC Copious, bloody - toxic patient HUS
polymerization and spread to adjacent cells No inflammation
o EIEC can invade by cell to cell EAEC Non - bloody -
Persistent diarrhea in children
Salmonella Non - bloody + Nausea, vomiting
Shigella Bloody, mucoid + Abdominal pain, tenesmus
Nausea, vomiting, abdominal
Vibrio
Rice - water stools - cramps, profound dehydration,
cholerae
circulatory collapse

Treatment
 Fluid and electrolyte therapy (most important)
 Antimicrobials
o Salmonella
 Ampicillin
 Trimethoprim – sulfamethoxazole
 3rd gen – cephalosporin
o Shigella
 Ciprofloxacin
 Ampicillin
 Doxycycline
o Vibrio
 Tetracycline

Enteroaggregative E. coli (EAEC)

 First recognized in 1897 as distinct from other ETEC
 Characteristic adhesion pattern in vitro reflects
bacteria – bacteria (in addition to bacteria – host)
adhesion