MMI 30: Lecture 21: Bordetella and Haemophilus

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  1. Whooping cough caused by:
    Bordetella pertussis
  2. Species related to Bordetella pertussis
    • B. parapertussis:
    • milder respiratory infection

    • B. brochiseptica:
    • kennel cough in dogs
  3. Vaccine used for whooping cough:
    Killed whole cell at first, acellular vaccine later
  4. Who cultured/identified B. pertussis
    • Jules Bordet
    • (Nobel Prize, worked at Pasteur lab)
  5. Bordetella pertussis Morphology
    Small, gram - bacilli
  6. Bordetella aerobics
  7. Growing Bordetella pertussis
    • Does not grow on common lab media
    • Needs (Bordet-Gengon) media (clinical labs usually need forewarning so they use this)
    • Colonies only visable after 3 days
  8. Bordetella's reservoir
    Strictly humans
  9. Discovered DTP Vaccine
    Pearl Kendrick
  10. DTP Vaccine
    • Diphtheria, Tetanus, Pertussis Vaccine
    • Aluminum adjuvant
    • All three act as adjuvants for each other, vaccine stronger for all three in presence of others.
  11. Bordetella pertussis disease/pathogenesis
    • Colonizes limited area: tracheobronchial epithelium
    • Disease from systemic spread of exotoxins from site of infection
    • Death in children mostly from pneumonia from secondary invaders (S. pneumoniae)
  12. Most common cause of infection from B. pertussis
    Inhalation of aerosol droplets from sneeze (highly contagious)
  13. Stages of Whooping cough
    • 1. Catarrhal: runny nose/sneezing/fever/malaise) 1-2 weeks. Organism can be isolated
    • 2. Paroxysmal coughing: Multiple cough followed by inspiratory gasp (the whoop) 2-4 weeks, organism hard to isolate
    • 3. Convalescence: Symptoms fade, this is when secondary infections can occur.
  14. Virulence factors of B. pertussis
    Pertussis Toxin (Ptx), Filamentous Hemagglutinin (FHA), Adenylate cyclase toxin, Trachael cytotoxin.
  15. Pertussis Toxin:
    • AB5 toxin
    • Carries out ADP-ribosylation of host protein
    • Modifies G-i-alpha
    •      -Inhibits cAMP production
    • Removal of inhibitor produces more cAMP, making mucus
    • Secreted by Type-IV system
  16. Filamentous Hemagglutinin (FHA)
    • Cell surface attachment factor
    • Promotes adherence of B. pertussis to tracheal ciliated cells.
  17. Type IV secretion system
    • Secrete protein or DNA and protein
    • Pertussis toxin is secreted by Ptl T4SS, contact-independent
  18. Adenylate cyclase toxin:
    • Bifunctional toxin
    • -Can be internalized into host cell and cause derailment of signal transduction by increasing cAMP levels
    • -At high concentrations can be cytolytic (hemolysin)
    • -Secreted by a Type 1 system
  19. Tracheal cytotoxin
    After B. pertussis attaches to cilia is prevents ability for those cells to move material upwards, including bacteria. Toxin consists of basic subunit of peptidoglycan
  20. B. pertussis's use of peptidoglycan
    Subunits usually used for new synthesis after being imported back into cell, B. pertussis secretes the units for tracheal toxin
  21. Treatment and prevention of B. pertussis
    • Antibiotics do not fix anything
    • Treat symptoms not cause
    • Vaccine is best hope
  22. Haemophilus morphology
    Small gram - bacilli (coccal-bacilli)
  23. Genera in family Pasteurellaceae:
    Haemophilus, Actinobacillus, Pasteurella
  24. Haemophilus aerobics
    Facultative anaerobes
  25. Growing Haemophilus
    Nutritionally fastidious
  26. Location of Haemophilus
    Not found in enviroment, obligate parasites of mucosal membrane
  27. Haemophilus endotoxin
    • Haemophilus has typical gram - cell wall
    • Endotoxin differs from enteric LPS in that it is lipooligosaccharide (LOS) which lacks repeating O- antigen carbohydrates
  28. Haemophilus capsules
    Most, not all, are encapsulated
  29. Haemophilus influenzae strain difference based on
    Capsule types, six antigenic types a-f, f most systemic diseases
  30. Nonencapsulated Haemophilus associated with
    Called nontypeable strains, associated with otitis and sinusitis
  31. Haemophilus growth requirements
    • Need:
    • Blood factors: hematin (X factor), nicotinamide adenine dinucleotide (NAD) (V factor)
    •     -This need can be used to identify
    • Grown on chocolate auger
    •       -Nutrient rich auger mixed with lysed red blood cells.
  32. Haemophilus can be seen where on throat cultures
    Satelliting colonies of organisms that lyse red blood cells producing the needed factors.
  33. Haemophilus reservoir
    • Obligate Mucosal Parasites
    • Historically believed to be already existing bacteria during compromised state
    • Now we know disease is from exposure to pathogenic strain
  34. Haemophilus disease
    Pre vaccine was relatively common in children , usually caused Meningitis, this was one of most common sources of mental disability.
  35. Diseases caused by Haemophilus influenzae B (Hibs)
    meningitis, bacteremia, cellulitis, epiglottis
  36. Diseases caused by non-typeable H. influenzae
    • Otitis media, bronchitis, sinusitis
    • Rarely bacteremia
  37. Pneumonia can be caused by both:
    Encapsulated and nontypeable Haemophilus
  38. Conjunctivitis
    • Caused by Haemophilus influenzae biotype aegyptius
    • "Pink-eye"
    • Also caused by adenoviruses
  39. Chancroid
    • Caused by Haemophilus ducreyi
    • -STI
    • -Week after exposure small lesion appears that develops into a painful ulcer, followed by inguinal lymphadenopathy
    • May increase risk of HIV
  40. Haemophilus pathogenesis
    • Capsule: Anti-phagocytic, involved with invasion past epithelial layers
    • IgA protease: Degrades IgA (main IgA of mucosal membranes, IgA prevents attachment, so this helps with attachment and colonization)
    • Pili: Found on nontypeable, enhance colonization, also have surface proteins (HMWs= high molecular weight proteins) that are homologous to adhesins used by Bordetella pertussis
    • Exotoxins: None-known, does have exoproteins (hemepexin is siderophore)
    • LOS Form Endotoxin: Haemophilus associated with toxicity to respiratory cilia, facilitates colonization of respiratory tract. LOS of this organism can undergo phase/antigenic variation.
  41. Treatment of Haemophilus
    Treatable with antibiotics
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MMI 30: Lecture 21: Bordetella and Haemophilus
MMI 301
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