LECTURE - Bordetella pertussis

Question 1

B. pertussis characteristics

Answer 1

• slow-growing organism (3-5 days)
• gram neg coccobacilli
• non-motile, non-spore forming
• looks like H. influenzae but no requirement for X and V factors
• special media needed to grow isolates = Regan-Low (charcoal) agar
• strict aerobe
• detected by PCR (best); direct fluorescent monoclonal Ab

Question 2

Three stages of B. pertussis disease

Answer 2

• Catarrhal stage: 5-10 days of cold-like symptoms
• Paroxysmal stage: 1-2 wks of sudden fits of evere, rapid, and sequential coughing until infected person “runs out of air”; stops coughing and suck air into lungs = whooping sound
• Convalescent stage: paroxysms decrease in number and frequency as immune system takes control

Question 3

T or F. B. pertussis is only found in humans

Answer 3

T! only reservoirs

Question 4

who gets whooping cough?

Answer 4

• children less than 2 yrs old can develop the most severe cases of whooping cough
• since early 1990’s = markedly increased # of cases in 10-14 yr old

Question 5

Disease progression and virulence factors of B. pertussis

Answer 5

• inhalation of aerosols
• bacteria either: adhere to epithelial cells OR adhere to phagocytes
• toxin production OR ingested
• damage to mucosal cells/act on neurons OR possible intracellular phase
• paroxysmal cough

Question 6

all aP have at least this component

Answer 6

Pertussis toxoid (weaker if not accompanied by other four)

Question 7

Current aP in Canada has five components:

Answer 7

• pertussis toxin (PT)
• Pertactin (Prn) = OM protein
• filamentous hemagglutinin (FHA)
• 2 types of fimbriae = Fim2, Fim3

Question 8

Pertussis toxin structure

Answer 8

• AB Toxin
  > A = S1 = enzymatically active
  > B = 2 S4, S5, S2, S3

Question 9

Pertussis toxin pathogenesis

Answer 9

• like cholera toxin BUT in respiratory tract
• adenylate cyclase system remains turned on
  > result similar but mechanism is different
• pertussis toxin modify GDP binding protein = Gi = turns off the off mechanism of the adenylate cyclase system
  = secretion of mucous and degranulation of immune cells

Question 10

T or F. wP vaccine produce a better Th1 respondse for B. pertussi than current aP vaccine and the immune response last longer

Answer 10

T! LOS was main reason why aP replaced wP

• rich countries have aP but poorer countries use wP
• LOS = adjuvant and endotoxic like response = modify!or remove LOS from whole cell

Question 11

two-component regulatory system of B. pertussis

Answer 11

• BvgAS
• can exist in two stable phenotypic forms = virulent or avirulent; Bvg + or Bvg -
• Bordetella ‘vir’ gene = regulates virulence
• rheostat; notan on/off switch = Bvg i

Question 12

these components of B. pertussis inhibit phagocyte migration and reduce oxidative burst

Answer 12

PT = pertussis toxin
ACT = adenylate cyclase toxin

Question 13

vaccination series of DTaP

Answer 13

• 2, 4, 6 months
• boosters at 18 months, 4 yrs old, and gr 9 (14-15 y/o)
• pregnant women in 3rd trimester get boosted as well

Question 14

two ways the effects of the BvgAS system can be manifested in B. pertussis

Answer 14

• Phenotypic
  > freely reversible effect on BvgS (sensor) by some environmental stimulus
  > identity of BvgS stimulus in vivo is currently unknown
  > in vitro = Mg 2= and 25 degrees Cstops BvgS from phosphorylating BvgA
• Phase variation
  > BvgS not expressed bc bvgS gene is mutated
  > occurs at spontaneous frequency of about 10^-6 = stable, “avirulent” form can be seen as flat, non-hemolytic colonies (Bordet-Gengou blood agar)