Lecture 1 - Infectious disease

Question 1

What are Koch’s postulates for proving that a specific microorganism causes a specific disease?

Answer 1

“It is essential that following isolation of a pure culture of the suspected pathogen, a laboratory culture of the organism should both initiate the disease and be recovered from the diseased animal”

Koch’s postulate #1:
The microorganism must be found in abundance in all organisms suffering from the disease, but should not
be found in healthy organisms.

Koch’s postulate #2:
The microorganism must be isolated from a diseased organism and grown in pure culture.

Koch’s postulate #3:
The cultured microorganism should cause disease when introduced into a healthy organism.

Koch’s postulate #4:
The microorganism must be re-isolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

Question 2

What is the type 3 secretion system?

Answer 2

molecular syringe
Actively injects bacterial proteins into host cell
Effectors affect e.g actin polymerisation, signalling

Question 3

What is vibrio cholera?

Answer 3

Colonizes small intestine
Mice not susceptible; infant rabbit model
Cholera toxin causes increased adenylate cyclase activity in host cell; cAMP levels up; changes sodium/chloride flux in-out of cell
Loss of fluid and electrolytes (diarrhea)
Additional virulence factors:
TCP adhesin; mucinase
Reservoir: ocean/ chitin surfaces

V cholera the etiologic agent of cholera
Host genetic and nutritional factors affect susceptibility to cholera. The ABH histo-blood group antigens are a set of cellular and secreted glycolipids and glycoproteins that are key determinants of host susceptibility to a number of gastrointestinal pathogens; they seem to affect host cell receptor specificity for pathogen and toxin binding.
Causes diarrhoea, massive amounts of water expelled
Cholera toxin is exotoxin - bacteria produces protein, is secreted and gets into host cell
Cells unable to retain water - damage to small intestine Flagellum allows motility

Question 4

Describe how blood group affects susceptibility to cholera

Answer 4

Role Vc flagella and mucinase for virulence
Role host: presentation of blood group antigen or not on intestinal cells/mucin
Nature of antigen determines cholera toxin binding affinity
Stronger binding: increased risk of cellular uptake

V. cholerae burrows through the mucus layer, aided by its flagellum and mucinases. After colonization, it produces the cholera toxin. CT’s interaction with the host cells depends on the person’s blood group and secretor status. In secretors, blood group antigens are expressed on mucins and intestinal epithelial cells. H-antigens (characteristic of blood group O) can bind the toxin in two orientations. They bind the toxin more strongly than A-antigens and therefore retain the toxin, increasing the risk of cellular uptake. CT has a lower affinity to A-antigens, and is therefore more easily ejected by the peristaltic movement of the intestine. This protects secretors with blood group A from severe disease, while blood group O individuals suffer more serious symptoms.

Question 5

What is EHEC?

Answer 5

Enterohemorraghic Escherichia coli
Serotype: O - O-antigen of LPS; H- flagella
Escherichia coli strain O157:H7
Targets small intestine.
Bloody diarrhoea
Produces Shiga toxin: extracellular cytotoxin
Targets ribosome (modifies rRNA in host), inhibits translation
induces signalling pathways,causes cell apoptosis
Hemolytic uremic syndrome (HUS) (in 10%); kidney damage
Additional virulence factors:
Adhesins and T3SS -Attaching and effacing phenotype: intestinal colonization (LEE PAI*)
mucinase
Reservoir: cattle