Bacterial Toxins

Question 1

What is the difference between endotoxins and exotoxins?

Answer 1

endotoxins are available for action following cell death, they are liposaccharides and found as part of the cell wall, they are resistant to heat and the lipid aspect is what stimulates immune system. They have low site specificity.

Exotoxins are secondary metabolites, with high potency and site specificity, more sensitive to temp changes, exhibit some sort of tissue tropism

Question 2

Endotoxins only found in what type of cell?

Answer 2

Gram negative

Question 3

What are the 3 groups of exotoxins?

Answer 3

Pore forming
Toxins with enzymatic activity
Superantigens

Question 4

What is the MoA of pore forming toxins?

Answer 4

they are water soluble molecules which bind to specific receptors within host membrane, receptor undergoes conformational changes, which causes the creation of an aq pore (essentially perforates cell membrane)

Question 5

What are some outcomes of the binding of pore forming toxins?

Answer 5

permeability to calcium, can result in the arrest of protein formation, the loss of potassium & net effect generally a cytolytic effect leading to cell death

Question 6

What is pneumolysin?

Answer 6

a pore forming toxin produced by Streptococcus pneumoniae, more than 90 capsular types, non-motile

Question 7

What receptor does pneumolysin bind to?

Answer 7

cholesterol, it’s a cholesterol dependent toxin and oligomerizes in membrane (forms a polymer)

Question 8

What does cytolytic means?

Answer 8

In high enough conc will result in cell death

Question 9

How is pneumolysin involved in the pathogenesis of CAP?

Answer 9

colonisation of the lung and histopathological changes in lung (changes in lung tissue)

Question 10

When do you see the early phase (immunosuppressive) and what happens during it?

Answer 10

Inhibition of mucociliary pathway and macrophage apoptosis. Early phase seen when it moves down to the lung

Question 11

What happens during the late phase (proinflammatory)?

Answer 11

Influx of neutrophils, complement activation, ROS production, inflammatory mediated tissue damage

Question 12

Signs and symptoms of CAP?

Answer 12

Fever, malaise, dyspnoea, productive cough

Question 13

What are the most common type of toxins with enzymatic activity?

Answer 13

AB toxins

Question 14

Describe the diphtheria toxin

Answer 14

Producing agent is C.diptheriae which is gram positive, non-motile and has clubbed morphology. The toxin can cause systemic effects such as heart complications, coma and even death but usually causes formation of a Pseudomembrane at the back of throat which causes difficulty swallowing

Question 15

What is the MoA of DT?

Answer 15

acquired via inhalation of aerosols, colonises the throat and produces single chained AB toxin. AB toxin split into two subunits (A subunit has enzymatic activity and B subunit involved in receptor binding on surface of eukaryotic cell and getting toxin into cells), AB toxin inhibits elongation factor 2 in eukaryotic cells which causes inhibition of tRNA translocation and in turn inhibits protein synthesis

Question 16

Describe the botulinum toxin

Answer 16

Producing agent is clostridium botulinum which is a gram positive motile rod, obligate anaerobe

Question 17

What is botulism?

Answer 17

A toxin mediated disease that causes flaccid paralysis through toxin mediated effect on peripheral nervous system

Question 18

Explain the MoA of BoNT

Answer 18

Toxin binds presynaptically to sites on the cholinergic nerve terminal and decreases the release of Ach from axons at the neuromuscular junction which then causes flaccid paralysis

Question 19

How does food borne botulism occur?

Answer 19

Toxin in contaminated food ingested then enters bloodstream and causes flaccid paralysis

Question 20

How does infant botulism occur?

Answer 20

Infant ingests spores which germinates and colonise GIT, enter blood stream and cause flaccid paralysis

Question 21

Why do spores ingested by infants germinate?

Answer 21

because they don’t have anything colonising their gut

Question 22

How does wound botulism occur?

Answer 22

wound contaminated with spores, toxin enters bloodstream and causes flaccid paralysis

Question 23

What is the clinical presentation of botulism?

Answer 23

diarrhoea and vomiting, blurred vision, difficulty speaking, progresses to paralysis

Question 24

What are some examples of superantigens?

Answer 24

TSST & streptococcal pyrogenic exotoxins

Question 25

Explain the process of T cell activation

Answer 25

In short, MHC class II molecules with peptide antigens which are expressed on the surface of APCS are presented to t cells causing them to bind and become activated. This starts with phagocytosis of microorganism then phagosome fuses with lysosome to degrade it and break down antigen into peptides, MHC class II molecules created within ER and you eventually end up with MHC II molecules with a bound peptide epitope

Question 26

What do superantigens do?

Answer 26

they bind MHC-II molecules, activate a lot of T cells and cause them to release cytokines

Question 27

Describe the toxic shock syndrome toxin and its clinical presentation

Answer 27

Produced by S. Aureus, involves multiple organ systems, causes fever, hypotension, a rash and desquamation of the skin on soles and palms

Question 28

What is pertussis?

Answer 28

Causative agent is Bordetella pertussis which is a gram-negative aerobic coccobacillus

Question 29

What are the symptoms of pertussis?

Answer 29

cough outbreaks

Question 30

What condition can pertussis progress to?

Answer 30

secondary pneumonia

Question 31

How are toxin mediated diseases treated/prevented?

Answer 31

vaccination, antibiotic management and use of anti-toxins for post exposure prophylaxis and for neutralization of effects)

Question 32

Describe all the toxins generated by pertussis

Answer 32

pertussis toxin (toxin enzymatic activity- immune inhibition), tracheal cytotoxin (endotoxin – mucociliary pathway inhibition) & adenylate cyclase toxin (pore forming and enzyme activity – immune inhibition)