MMI 30: Lecture 21: Bordetella and Haemophilus

Bordetella pertussis

• B. parapertussis:
• milder respiratory infection

• B. brochiseptica:
• kennel cough in dogs

Killed whole cell at first, acellular vaccine later

• Jules Bordet
• (Nobel Prize, worked at Pasteur lab)

Small, gram - bacilli

Aerobic

• 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

Strictly humans

Pearl Kendrick

• Diphtheria, Tetanus, Pertussis Vaccine
• Aluminum adjuvant
• All three act as adjuvants for each other, vaccine stronger for all three in presence of others.

• 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)

Inhalation of aerosol droplets from sneeze (highly contagious)

• 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.

Pertussis Toxin (Ptx), Filamentous Hemagglutinin (FHA), Adenylate cyclase toxin, Trachael cytotoxin.

• 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

• Cell surface attachment factor
• Promotes adherence of B. pertussis to tracheal ciliated cells.

• Secrete protein or DNA and protein
• Pertussis toxin is secreted by Ptl T4SS, contact-independent

• 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

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

Subunits usually used for new synthesis after being imported back into cell, B. pertussis secretes the units for tracheal toxin

• Antibiotics do not fix anything
• Treat symptoms not cause
• Vaccine is best hope

Small gram - bacilli (coccal-bacilli)

Haemophilus, Actinobacillus, Pasteurella

Facultative anaerobes

Nutritionally fastidious

Not found in enviroment, obligate parasites of mucosal membrane

• Haemophilus has typical gram - cell wall
• Endotoxin differs from enteric LPS in that it is lipooligosaccharide (LOS) which lacks repeating O- antigen carbohydrates

Most, not all, are encapsulated

Capsule types, six antigenic types a-f, f most systemic diseases

Called nontypeable strains, associated with otitis and sinusitis

• 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.

Satelliting colonies of organisms that lyse red blood cells producing the needed factors.

• Obligate Mucosal Parasites
• Historically believed to be already existing bacteria during compromised state
• Now we know disease is from exposure to pathogenic strain

Pre vaccine was relatively common in children , usually caused Meningitis, this was one of most common sources of mental disability.

meningitis, bacteremia, cellulitis, epiglottis

• Otitis media, bronchitis, sinusitis
• Rarely bacteremia

Encapsulated and nontypeable Haemophilus

• Caused by Haemophilus influenzae biotype aegyptius
• "Pink-eye"
• Also caused by adenoviruses

• 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

• 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.

Treatable with antibiotics