GENERAL PRINCIPLES

• Gram-negative Rods
• Colon microbiome
  – E. coli are common members of the colon microbiome.
  – Opportunistic pathogens: upon transfer to new anatomical niches, these strains can cause endogenous infections.
• Found in soil and water
  – As a result of animal or human fecal contamination.
  – Upon ingestion, pathogenic strains cause exogenous infections in humans.
• Because they reside in the intestines of animals and humans, E. coli are “enteric” bacteria.
• E. coli common pilus
  – Aids in adhesion to host surface and biofilm formation.
• Flagellar motility facilitates movement.
• Rapid growth
  – Simple nutritional requirements
• Facultative anaerobe
• Catalase-positive
• Oxidase-negative
• Reduce nitrate
• Ferments glucose
• Ferments lactose
  – Coliforms: Gram-negative enteric lactose fermenters.
  – Also includes strains from Klebisella, Serratia, Klebsiella, and Citrobacter.
  – Eosin methylene blue agar and MacConkey’s agar are two types of selective media used to identify coliforms; both inhibit Gram-positive bacterial growth and signify acid production from lactose fermentation.
  EMB agar: lactose fermentation and strong acid production yield a characteristic greenish hue.
  MacConkey’s agar: E. coli lactose fermentation produces a pinkish-purple color.

COMMON VIRULENCE FACTORS

Many virulence factors are acquired via horizontal gene transfer of plasmids, bacteriophages, and pathogenicity islands.

• E. coli endotoxin comprises heat-stable lipopolysaccharide:
  – Its A-antigen has classic endotoxin activity: it triggers the host inflammatory responses, disseminated intravascular coagulation, and hypovolemic shock.
  – The core polysaccharide is common to all Enterobacteriaceae.
  – The O-antigen is used to classify E. coli serotypes.
• Exotoxins promote cell death or fluid loss.
• Adhesins are present on pili, fimbriae, or strain-specific surface antigens.
• Type III secretion systems inject virulence effector proteins into host cells.
  – Virulence effectors promote attachment, invasion, and cell destruction.
• Phase variation alters the expression of O, K, and flagellar H antigens and pili.
  – Alteration of surface antigens allows E. coli to avoid host immune system and, possibly, to adjust energy expenditure according to environmental factors.
• Antibiotic resistance
  – Resistant phenotypes are rapidly spread via HGT, which makes antibiotic treatment of E. coli infections particularly difficult.
• Siderophores, special receptors, and transporters
  – Acquire iron from the host; recall that iron is necessary for bacterial growth.
• Polysaccharide capsule lends repels phagocytes and avoids serum killing.

E. COLI INFECTIONS

Extraintestinal Infections

• Causative strains are called Extraintestinal pathogenic E. coli (ExPEC).
• ExPEC are often commensals that act as opportunistic pathogens when exposed to new anatomical sites.

• Urinary Tract Infections
  – Uropathic E. coli (UPEC) causes most urinary tract infections.
  – Adhesins: Type 1 and P pili and Dr fimbriae attach to urothelium.
  – Hemolysin A causes cell damage and facilitates bacterial movement through superficial cell layers.
  – Strains lacking these virulence factors are easily removed from the body in the urine.

• Neonatal Meningitis
  – E. coli is the second most common cause of bacterial neonatal meningitis.
  – Neonatal Meningitis-causing E. coli (NMEC) have special virulence factors that enable translocation across the blood-brain barrier:
  Type I pili and Outer Membrane Protein A (OmpA) attach to brain microvascular endothelial cells.
  Ibe (invasion of brain endothelial cells) proteins, CNF1 (cytotoxic necrotizing factor 1) and other mediators facilitate invasion of the blood brain barrier.
  K1 capsular antigens are thought to prevent lysosome fusion to allow successful movement of live bacteria across the barrier.

• Septicemia
  – Septicemia can occur when urinary or gastrointestinal tract infections spread to the blood; this can happen, for example, upon trauma to the abdomen.

Gastroenteritis

• E. coli pathotypes responsible for gastroenteritis are collectively referred to as “Intestinal Pathogenic E. coli” (IPEC).
  Infection typically follows ingestion of contaminated food or water; human or animal feces is often the source of the bacteria.
• IPEC can affect the small and/or large intestine:
  – Small intestine: Enteropathogenic E. coli and Enterotoxigenic E. coli
  – Small and Large intestines: Enteroaggregative E. coli
  – Large intestine: Enteroinvasive E. coli and Shiga toxin-producing E. coli
  Virulence factors specific to each pathotype determine the pathogenesis of infection.