2017/18-Essay 1

Question 1

Title

Answer 1

Invasion Tropism of Enterohaemorrhagic E. coli: Facilitating Toxin Dissemination to Different Organs

Question 2

Introduce the question

Introduction

Describe the invasion tropism shown by **enterohaemorrhagic E. coli **in the small and large intestine and **how **this facilitates toxin dissemination to different organs.

Answer 2

• EHEC
• Strain of E.coli
• causes sever gastrointestinal infections in humans
• Key characteristic = Shiga toxins
• Result: life threatening condition (HUS)
• > Haemolytic uremic syndrome
• Achieves colonisation+ toxin dissemination exibiting invasion tropisms (small and large intestines) discussed in this essay.

Question 3

Invasion Tropism in the Small Intestine: GB3 and T3SS

Paragraph 1

Describe the invasion tropism shown by **enterohaemorrhagic E. coli **in the small and large intestine and **how **this facilitates toxin dissemination to different organs.

Answer 3

Small Intestine
* Bacteria- specialised surface appendages
* structure>pilli and fimbriae
* why>attach to and colonise intestinal mucosa
* How>GB3 receptor small intestine (highly expressed surface of intestinal epithelial cells)
Upon attachment…
Type III secretion system
* (T3SS)- inject effector proteins ->host cells
* function of protein> manipulate hosts cytoskeleton, induce formation of actin pedestals beneath the attached bacteria
* Why pedestal formation? >EHECs - avoid peristalsis + remain attached to intestinal epithelium (enhances colonization and persistence)

Question 4

Invasion tropism in the large intestine: M cells

Paragraph 2

Describe the invasion tropism shown by **enterohaemorrhagic E. coli **in the small and large intestine and **how **this facilitates toxin dissemination to different organs.

Answer 4

Large Intestine
* Diff environemental conditions compared to small intestine
* Facilitated by M (microfold) cells interactions that overlie the lymphoid follicles of Peyer’s patches
* role> antigen sampling, immune response initiation, uptake of pathogens (EHEC)
* EHEC shown to exploit M cell sampling function > access to underlying tissues
* crossing intestinal barrier
* EHEC> interact w/immune cells and disseminate through bloodstream ->systemic infections

Question 5

Toxin Dissemination to Different Organs

Paragraph 3

Describe the invasion tropism shown by **enterohaemorrhagic E. coli **in the small and large intestine and **how **this facilitates toxin dissemination to different organs.

Answer 5

Different Organs
* Virulence factor: Shiga toxins (Stx)
* Once established in the intestines (produces shiga toxin)
* Shiga toxin: target cells expressing GB3 receptor
* >abundant in endothelial cells of various organs- Kidneys, Brain, and Pancreas

Kidneys
* Complication: Haemolytic-uremic syndrome (HUS)
* Shiga toxins: eneter blood stream, bind to GB3 receptors
* On renal endothelial cells
* Causes damage to small blood vessels
* >triggers cascade of events > HUS

Brain
* Neurological complication
* > seizures and encephalopathy
* Shiga toxin cross blood-brain barrier
* Affect neurons, glial cells (GB3 receptors)
* Contribute neurological damage

Pancreas
* Impaired insulin secretion
* Disrupton to blood glucose regulation

Question 6

Summary and Importance

Conclusion

Describe the invasion tropism shown by **enterohaemorrhagic E. coli **in the small and large intestine and **how **this facilitates toxin dissemination to different organs.

Answer 6

• Vital role in pathogenesis
• Targeting specific recdeptors on intestinal epithelium
• Exploiting M cell interaction
• EHEC gain entry to bloodstream, disseminated Shiga toxins
• Causing life threatning complications

Understanding mechanism Importance
* Development of effective treatment
* Preventative strategies against dangerous pathogen