7. Whooping Cough

Question 1

Similarities between Cholera and Whooping Cough (pertussis)

Answer 1

Both Gram neg
Both colonise
Both produce complex A-B toxin
Both have ADP-ribosylase activity (acts on G protein to increase cAMP)

Question 2

Differences between Cholera and Whooping Cough

Answer 2

Cholera: tropism for GI cells
Whooping cough: tropism for respiratory tract cells
Cholera: diarrhoea
Whooping cough: coughing
Similarities but have different target sites in the body → different primary symptoms

Question 3

What bacterium causes whooping cough?

Answer 3

Bordetella pertussis

Question 4

Features of Bordetella pertussis

Answer 4

Gram neg
Coccobacillus
Fastidious
Humans only reservoir

Question 5

What part of the body becomes infected by Bordetella pertussis?

Answer 5

Respiratory tract

Question 6

How is B. pertussis spread?

Answer 6

Spread by aerosols, direct contact e.g. coughing into hands & not washing hands

Question 7

What does initial whooping cough infection resemble?

Answer 7

The common cold

Question 8

What are the symptoms of whooping cough that begin to develop?

Answer 8

Severe paroxysmal (short & frequent, stereotyped symptom) cough, excess mucous & vomiting, can progress to irreversible neurological damage

Question 9

What are the 3 stages of whooping cough disease?

Answer 9

1. Catarrhal (7-10 days after exposure) - cold-like symptoms with hacking cough, fever rare
2. Paroxysmal (10-14 days after exposure) - fits of consecutive coughs followed by gasps for air (‘whoop’ noise)
3. Convalescent (4-6 weeks after exposure) - coughing fits gradually decrease although can recur for months when triggered by a respiratory infection

Question 10

Is whooping cough primarily a disease of children or adults? Why?

Answer 10

Primarily children since most adults have been exposed to the organism as children

Question 11

What lead to a decrease in vaccine uptake & resurgence of whooping cough?

Answer 11

Perceived risk of side effects i.e. brain bleeds

Question 12

What type of vaccine for pertussis was created after the brain bleed scare?

Answer 12

An acellular vaccine (aPV), which is not as effective as the host cell vaccine

Question 13

Who are more commonly associated with severe pertussis?

Answer 13

Naive infants

Question 14

Inhalation
Colonisation
Toxin production

Answer 14

Pathogenesis of pertussis in 3 steps?

Question 15

What is the main issue with animal models of pertussis?

Answer 15

Very poor symptom mimicry

Question 16

What cells are B. pertussis highly specific for?

Answer 16

Ciliated respiratory mucosal cells (alcohol paralyses these cilia)

Question 17

What happens after colonisation by B. pertussis?

Answer 17

The ciliated respiratory cells die - prevents removal in the normal manner (involves several adhesins)

Question 18

What is Fha?

Answer 18

FHa is filamentous haemagglutinin. It is a very elongated single surface protein which forms loose filamentous structures on the cell surface. It binds to sulfatide, found on the surface of tracheal cells

Question 19

To what does filamentous haemagglutinin bind?

Answer 19

Sulfatide

Question 20

What do Fha mutants exhibit?

Answer 20

Reduced colonisation

Question 21

What are the 2 roles of the pertussis toxin?

Answer 21

• As an adhesin

- As a toxin

Question 22

Pertussis toxin mutants are…

Answer 22

avirulent

Question 23

What type of toxin is the pertussis toxin?

Answer 23

A complex A-B toxin, composed of S subunits
S1 = A subunit
S2, 3, x2 S4, S5 = equivalent to 5B subunits

Question 24

S2 and S3 subunits of pertussis toxin mediate binding to?

Answer 24

Lactosylceramide (a glycolipid)

Question 25

What is the active subunit of the pertussis toxin?

Answer 25

S1 subunit - an ADP-ribosylase that acts on host G protein to affect cAMP levels

Question 26

How do the cholera toxin and pertussis toxin slightly differ in mode of action?

Answer 26

Ptx prevents release of GDP (by targeting Gi protein) → AC complex permanently switched on Cholera toxin permanently switches on AC complex by targeting the Gs protein

Question 27

What bacterium also causes the cough but does not produce Ptx?

Answer 27

Bordetella parapertussis

Question 28

What are 3 other toxins produced by B. pertussis?

Answer 28

1. Invasive adenylate cyclase (AMP is converted to cAMP via ACase (+calmodulin) to open ion channels) 2. Tracheal cytotoxin (kills ciliated cells in tracheal rings, stimulates IL-1 release - fever) 3. Dermonecrotic toxin (causes skin lesions (necrosis) at low concentrations, role in whooping cough is unclear)

Question 29

What host protein does invasive adenylate cyclase (ACT) require for full activity?

Answer 29

Calmodulin

Question 30

ACase mutants are?

Answer 30

avirulent

Question 31

Expression of virulence genes (pertussis) enhanced in what conditions?

Answer 31

High temp., low magnesium conc., low nicotinamide

Question 32

Treatment for pertussis?

Answer 32

Antibiotics do not influence the duration of the illness but may limit the infectivity. Best solution would be the development of better vaccines. Current best aPV not as effective as whole cells (in terms of duration of protection).