Molecular Mechanisms of Bacterial Toxins

Question 1

What do bacterial toxins do?

Answer 1

Cause damage to cells, tissues or the whole host organism

Question 2

What are the bacterial toxins?

Answer 2

Exotoxins
Endotoxins

Question 3

Describe exotoxins

Answer 3

Proteins released by G+ve and G-ve bacteria

Question 4

Describe endotoxins

Answer 4

Powerful immunostimulants
Portion of LPS found in G-ve cell walls also lipotheicoic acids of G+ve

Question 5

Give examples of exotoxins

Answer 5

Cytotoxins
Enterotoxins
Neurotoxins
Leukocidins
Ciliostatic toxins

Question 6

What are the types of toxins?

Answer 6

Classified by site of action
Type 1 = at cell membrane, not transported in
Type 2 = on cell membrane, membrane damage
Type 3 = intracellular effect after translocation
Extracellular = cellular matrix or connective tissue

Question 7

What bacteria causes Whooping cough?

Answer 7

Bordatella pertussis

Question 8

What are the toxins produced by Bordetella pertussi?

Answer 8

Invasive adenylate cyclase
Lethal toxin (dermonecrotic toxin) - superantigen
Tracheal cytotoxin
Pertussis toxin (PTx)

Question 9

What regulates bacterial toxin production?

Answer 9

Regulatory elements that are sensitive to environmental signals found in the host

Question 10

What regulates Diphtheria toxin?

Answer 10

Totally repressed by adequate iron
Limiting iron i.e. in blood means toxin is expressed

Question 11

What regulates cholera toxin and related virulence factors?

Answer 11

Environmental osmolarity and temperature

Question 12

Describe phase variation and antigenic modulation in Bordetella pertussis

Answer 12

BvgA/S sensor and regulator senses environmental signals and activates VIR gene
Activation of positive effector protein that binds to virulence genes across the genome
Negative effectors can also be activated and switch off genes that are not needed

Question 13

What are the pathogenic mechanisms of Strep pneumoniae?

Answer 13

Colonisation
Bypass defences
Survival
Damage
e.g. Pneumonia, Otitis media, Meningitis

Question 14

Describe how Strep pneumoniae causes infection

Answer 14

Colonises nasopharynx as it expresses secretory IgA proteases that degrade any protective Ig at the surface of mucosa
Inhalation into lungs
Bypasses defences - surfactants due to sIgA and pneumolysin (damages membranes of pneumocytes in the lower lung)
Reaches lung
Escapes phagocytosis due to capsule
Inflammation and lung damage
Damage to endothelial cells
Pneumonia, bacteraemia, meningitis and septicaemia

Question 15

What is antigenic variation?

Answer 15

Successive expression of alternative forms of an antigen in a specific clone or its progeny

Question 16

What is antigenic diversity/polymorphisms?

Answer 16

Genetically stable and alternative forms of antigens in a population of microbes
e.g. serotypes of Strep. pneumoniae

Question 17

What is phase variation?

Answer 17

Activation/deactivation of an Ag at low frequency
Occurs during course of infection in an individual host and during spread of the microbe through a community

Question 18

What are the functions of toxins in infection?

Answer 18

Promote survival or spread of bacteria
Damage or destroy cells/cell membranes
Interfere with cell metabolism
Affect nerves
Interfere with normal immune function
Survival, growth and transmission

Question 19

Describe the difference in structure of gram positive and negative bacteria

Answer 19

G+ve have lipoteichoic acids traversing the cell wall and anchored in the basement membrane
G-ve have O antigens, porins, lipid A and lipoproteins

Question 20

What does LPS consist of?

Answer 20

Lipid A
Core antigen
O-polysaccharide
Lipooligosaccharide

Question 21

Describe Lipid A

Answer 21

Lipid component
Hydrophobic, membrane-anchoring region of LPS
Phosphorylated N-acetylglucosamine dimer with 6-7 fatty acid chains
Highly conserved cross G-ve species

Question 22

Describe the core antigen

Answer 22

Short chain of sugars
2 unusual sugars - heptose and KDO
KDO is unique and invariable present and is used as an indicator in assays for LPS

Question 23

Describe O polysaccharide

Answer 23

Repeating oligosaccharide subunits made of variable sugars
Vary in length ranging up to 40 repeat subunits
Hydrophilic domain
Major antigenic determinant
Virulence determinant as loss of O antigen = loss of virulence