Bacterial Pathogens And Disease I - Exotoxins

Question 1

What is an exotoxin?

Answer 1

Heterogenous group of proteins produced and secreted by LIVING bacterisl cells.

Question 2

What is type of bacteria is an exotoxin produced from?

Answer 2

Living and by both gram negative and gram postive bacteria.

Question 3

Why do we have exotoxins? (5)

Answer 3

To 
Evade immune response 
Enable biofilm formation 
Enable attachment to host cells 
Escape from phagosomes 
May help with transmission of disease (in severe disease, host may be a literal and evolutionary dead end)

Question 4

What selective advantage do exotoxins give to the bacteria? (3)

Answer 4

Allow for colonisation, niche establishment and carriage - evolutionary advantage

Question 5

Case of Staphylococcus aureus

Answer 5

Haemolytic toxins:
Cause cells to lyse by forming pores
Important cause of features of S. aureus disease
(alpha, beta toxins, Panta Valentine Leukocidin (PVL), LukAB, LukEd, LukMF
Phenol soluble modulins PSM
Aggregate the lipid bilayer of host cells - lysis

Majority of it is found in the asymptotic carriage in the nose.

Question 6

What are those toxins doing in the nose?

Answer 6

A
B
C
D

Question 7

Genetics of exotoxins

Answer 7

Can be encoded by chromosomal genes
E.g.’s Shiga toxin in Shigella dysenteriae, TcdA & TcdB in C. Difficile

Many toxins coded by extrachromosomal genes

• Plasmids -> Bacillus anthracis toxin, tetanus toxin
• Lysogenic bacteriophage -> streptococcal pyrogenic exotoxins in Scarlet Fever, Diphteria toxin

Question 8

Classification of Exotoxins

Answer 8

Classified by exotoxin activity:

1) Membrane Acting Toxins - Type I
2) Membrane Damaging Toxins - Type II
3) Intracellular Toxins - Type III

Question 9

What are the problems with Classification of exotoxins?

Answer 9

Many toxins may have more than one type of activity.

As mechanisms are better understood, this classification tends to break down.

Question 10

Membrane Acting Toxins - Type I

Answer 10

Act: From outside the cell - without the cell

Interfere: With host cell signalling by inappropriate activation of host cell receptors

Target: Receptors include:
Guanylyl Cyclase
Adenyl Cyclase 
Rho proteins 
Ras proteins

Question 11

Type I - E. coli stable Heat toxin

Answer 11

Picture

Question 12

Membrane damaging toxins - Type II

Answer 12

Cause damage to the host cell membrane.

1) insert chnnae,s into host cell membrane.
- beta sheet toxins e.g. S.aureus alpha - toxin, to in, PVL
- alpha helix toxins - e.g. diphtheria toxin
2) Enzymatical damge e.g, S.aureus beta - haemolysin, PSM

Or

1) Receptor mediated
2) Receptor independent

Question 13

Membarne damaging toxins diagram

Answer 13

Diagram

Question 14

Intracellular toxins - Type III

Answer 14

Active within the cell - must gain access to the cell
Usually 2 componesnt- AB toxins
- receptor binding and translocation function- B
- Toxigenic (enzymatic) - A
May be sigle or multiple B units e.g. Cholera toxin AB5

Question 15

Intracellular toxins - Type III- AB Toxins

Answer 15

Enzymatic Component A - wide variety of activities
ADP - ribosyl transferases e.g. Exotoxin A of Pseudomonas aeruginosa, pertussis toxin
Gluosyltransferases e.g. TcdA + TcdB of C. difficile
Deamidase e.g. dermonecrotic toxin of Bordetella pertussis
Protease e.g. Clostridia, neurotoxins: Botulism + Tetanus
Adenylcyclase e.g. EF (Edema factor) toxin of Bacillus anthracis

Question 16

Intracellular toxins - Type III- other

Answer 16

Diagrams

Question 17

Superantigens and Inflammatory Cytokines

Answer 17

Exotoxins are able to induce inflammatory cytokine release

IL1, IL1 beta , TNF, IL6, interferon, IL18

Question 18

Superantigen mechanisms

Answer 18

Non specific briding of the MHC Class II and T- cell receptor leading to cytokine production.
E.g. Staphlococcal Exoliative Toxin A, Toxic Shock Syndrome Toxin 1 (TSST1)

Via activation of the different inflammasome leading to release IL1 beta and IL18 e.g. S. aureus toxin