Urogenitary infections

• Describe enteropathogenic E. coli

  • Causes infant diarrhoea in many developing countries
  • Diarrhoea results from multiple mechanisms:
  • Active ion secretion
  • Increased intestinal permeability
  • Intestinal inflammation
  • Induces characteristic attaching and effacing lesions on epithelial cells
• Describe the pathogenic mechanisms of enteropathogenic E. coli

  • EPEC is an extracellular pathogen that binds to host cell surfaces using bundle forming pili
  • EPEC injects a variety of effector proteins into the host cell using a type III secretion system, which:
  • changes formation of attachment and effacing structures on epithelial cells
  • effacement: destruction of microvilli with production of lesion by T3SS effector protein mediated cytoskeleton changes involving actin polymerisation
• Describe enterohaemorrhagic E. coli

  • Leads to diarrhoea
  • Causes similar attaching and effacing activity to EPEC but in the colon
  • Produces Shiga toxin, which can cause life threatening complications
• Describe EHEC shiga toxin

  • A1B5 type toxin
  • B subunit forms a pentamer which can bind to Gb3 glycolipid
  • A subunit cleaves 28S rRNA component of the ribosome, which halts protein synthesis.
  • Toxin is taken up through endocytosis and transported in a retrograde manner through the golgi/ER, before the A1 domain is released into the cytosol.
• Describe the T3SS

  • Inject bacterial effector proteins directly into the host cell cytoplasm
  • Interfere with host cell cytoskeleton to promoter attachment and invasion
  • Activity of T3SS correlates with infection outcome
  • EspF recruits Arp2/3
• What is EtpA?

  This is found in ETEC strains and is a two partner secretion protein A. It is transiently located at the tip of the ETEC flagella and bridges across the flagella tip with host cell receptors. This mediates ETEC attachment to epithelial cells.
• Describe ETEC toxins

  • Heat stable toxin
  • STa and STb families, STa is associated with human disease
  • STa mimics guanylin which binds to guanylate glucose on intestinal epithelial cells
  • Cysteine rich so forms intramolecular disulphide bonds, which are important for structure
• Describe the bacterial pathogenicity islands in EPEC and EHEC

  bacteria

  • Contain all the genes for attaching and effacing
  • Known as locus of enterocyte effacement
  • EPEC contains LEE pathogenicity island, which can be transferred into other strains and confer ability to produce lesions.
  • LEE gene products synthesise T3SS